| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Polymorphism at the LDL receptor gene locus in patients with cholesterol gallstone disease Feng, D., T. Han, et al. (1998), Zhonghua Yi Xue Za Zhi 78(1): 63-5. Abstract: OBJECTIVE: To investigate the association between the dinucleotide repeat polymorphism at the 3' end of the LDL receptor gene and cholesterol gallstone disease. METHODS: Polymorphism of the (dTA)n was amplified by using polymerase chain reaction, and the alleles identification was performed with denaturing polyacrylamide gel electrophoresis and silver stain technique. RESULTS: Analysis of allele frequencies in 131 unrelated Chinese gallstone patients and 79 controls indicated that the C allele was more frequent in the patients with cholesterol gallstones than that in the controls (0.40 vs 0.27, P < 0.01), and the frequency of the BB genotype of the LDL receptor gene was markedly lower (P < 0.005), while the CC and BC genotypes were significantly higher in the patients with cholesterol gallstones than in the controls respectively (P < 0.05, P < 0.05). CONCLUSION: The present study suggests that the LDL receptor gene polymorphism may be associated with cholesterol gallstone disease. |
| Polymorphism exon 1 variant at the locus of the scavenger receptor class B type I gene: influence on plasma LDL cholesterol in healthy subjects during the consumption of diets with different fat contents Perez-Martinez, P., J. M. Ordovas, et al. (2003), Am J Clin Nutr 77(4): 809-13. Abstract: BACKGROUND: The association between polymorphisms in the scavenger receptor class B type I (SRB-I) gene and variations in basal plasma concentrations of cholesterol in humans has recently been described. OBJECTIVE: The objective of the study was to determine whether the exon 1 variant (G-->A) at the SRB-I gene is associated with the lipid response to the content and quality of dietary fat in healthy subjects. DESIGN: We studied 97 healthy volunteers with exon 1 polymorphism 65 homozygous for allele 1 (1/1) and 32 heterozygous for allele 2 (1/2). Both groups consumed 3 diets lasting 4 wk each. The first was a saturated fatty acid (SFA)-rich diet (38% fat, 20% SFA), which was followed by a carbohydrate (Cho)-rich diet (30% fat, < 10% SFA, 55% carbohydrate) or a monounsaturated fatty acid (MUFA), olive oil-rich diet (38% fat, 22% MUFA) according to a randomized crossover design. At the end of each dietary period, plasma concentrations of triacylglycerol and of total, LDL, and HDL cholesterol were measured. RESULTS: Carriers of the 1/2 genotype had a trend toward higher concentrations of LDL cholesterol (P < 0.11) after the SFA-rich diet than did those who were homozygous for 1/1. Carriers of the mutation showed a significantly greater (P = 0.007) decrease in LDL-cholesterol concentrations (-23%) in changing from an SFA-rich diet to a Cho-rich diet than did noncarriers of the mutation (-16%). CONCLUSION: Carriers of the minority allele, 1/2, are more susceptible to the presence of SFA in the diet because of a greater increase in LDL cholesterol. |
| Polymorphism in intron 2 of islet amyloid polypeptide gene is associated with lower low-density lipoprotein cholesterol in nondiabetic subjects and in type 2 diabetic patients Rojas, I., R. Gomis, et al. (2002), Endocrine 19(2): 185-9. Abstract: The aim of this study was to investigate the presence of mutations in the islet amyloid polypeptide (IAPP) gene in a Spanish population with type 2 diabetes and gestational diabetes mellitus (GDM). Using polymerase chain reaction single-stranded conformation polymorphism, we examined the coding region and the 5'-untranslated region (UTR) of the IAPP gene in 177 unrelated type 2 diabetic patients, 110 healthy control subjects, 38 women with GDM, and 38 gestational control subjects. Mutations were confirmed by DNA sequencing. A heterozygous C-to-A nucleotide substitution at +79 bp in intron 2 of the IAPP gene was detected. The frequencies of the +79-bp polymorphism (A allele) were 6.8% in type 2 diabetic patients, 7.7% in nondiabetic control subjects, 11.8% in women with GDM, and 9.2% in gestational control subjects. No AA genotypes were detected. Nondiabetic subjects and patients with type 2 diabetes bearing the CA genotype had lower low-density lipoprotein (LDL) cholesterol levels than subjects bearing wild genotype. Multivariate logistic regression analysis showed an independent association (p < 0.001; odds ratio: 0.33; 95% confidence interval: 0.17-0.63). We did not detect any sequence variant within exons 1 or 2. One diabetic patient was heterozygous for a silent mutation at codon 31 of exon 3 (Asn31 AAC --> AAT). Our findings indicate that the presence of the +79-bp polymorphism of the IAPP gene in nondiabetic subjects and in patients with type 2 diabetes is associated with lower levels of LDL cholesterol. Furthermore, abnormalities of the coding regions or the 5'-UTR of the IAPP gene are not associated with type 2 diabetes or GDM in the Spanish population. |
| Polymorphism in the cholesterol 24S-hydroxylase gene is associated with Alzheimer's disease Kolsch, H., D. Lutjohann, et al. (2002), Mol Psychiatry 7(8): 899-902. Abstract: Cholesterol and 24S-hydroxycholesterol are involved in the pathogenesis of Alzheimer's disease (AD). Increased serum cholesterol concentrations have been detected in patients with AD. 24S-Hydroxycholesterol is the primary cholesterol elimination product of the brain and possesses neurotoxic properties in vitro. The enzyme catalyzing the conversion of cholesterol to 24S-hydroxycholesterol, cholesterol 24S-hydroxylase (CYP46), is mainly expressed in neurons. Concentrations of 24S-hydroxycholesterol in cerebrospinal fluid (CSF) and serum differ significantly between AD patients and non-demented subjects. To test the hypothesis if polymorphisms in the CYP46 gene might influence the function of the respective enzyme and thus cholesterol metabolism in the human brain, we screened for polymorphisms in 114 AD patients and 144 healthy controls. Two intronic single nucleotide polymorphisms were observed and their allelic distribution was investigated. In our study sample, carriers of the C allele of the IVS3+43C --> T polymorphism were more prevalent in the group of AD patients than in healthy controls, while another IVS2-150A --> G polymorphism did not show a significant association with AD. The CC genotype of the IVS3+43C --> T polymorphism was associated with an increased 24S-hydroxycholesterol/cholesterol ratio in the CSF of AD patients. Our results indicate that the CYP46 gene locus may predispose to AD by increasing the 24S-hydroxycholesterol/cholesterol ratio in the brain. |
| Polymorphism in the regulatory part of the cholesterol 7 alpha hydroxylase gene in children with high and low levels of cholesterol Hubacek, J. A., H. Pistulkova, et al. (2003), Cas Lek Cesk 142(7): 423-6. Abstract: BACKGROUND: High plasma cholesterol is one of the risk factors of atherosclerosis. Both environmental (diet, physic activity) and genetic factors have been concerned in the development of hypercholesterolemia. Cholesterol 7 alpha hydroxylase (CYP-7A1) is a key enzyme in the bile acid synthesis and it plays an important role in cholesterol catabolism. The aim of the study was to establish the role of A-204-->C polymorphism in CYP-7A1 gene in plasma lipid determination in children. METHODS AND RESULTS: Using PCR and restriction analysis (BsaI) we have measured A-204-->C polymorphism in CYP-7A1 gene in two groups of children selected from opposite ends of the cholesterol distribution curve of 2000 children. Eighty-two children in high- (HCG) and eighty-six children in low- (LCG) cholesterolemic groups participated in the study. No significant difference was found in the frequencies of the genotypes or alleles of the A-204-->C polymorphism in the CYP-7A1 gene between HCG and LCG. In HCG, C/C-204 homozygotes have the highest and A/A homozygotes the lowest levels of LDL-cholesterol (4.21 +/- 0.68 mmol/l vers. 3.69 +/- 0.60 mmol/l, p < 0.05). No associations between lipid parameters and genotypes within the LCG group were found. CONCLUSIONS: The A-204-->C polymorphism in the gene for CYP-7A1 is not the major determinant of plasma lipid levels in childhood. Its impact is expressed only on high cholesterol background. |
| Polymorphism of HL +1075C, but not -480T, is associated with plasma high density lipoprotein cholesterol and apolipoprotein AI in men of a Chinese population Fang, D. Z. and B. W. Liu (2002), Atherosclerosis 161(2): 417-24. Abstract: Eight hundred and twenty-three Chinese Han adults aged over 40, including 466 men and 357 women were enrolled in the study to examine the association of +1075C and -480T polymorphisms in hepatic lipase gene with plasma lipoprotein and apolipoprotein levels. In this population the allele frequencies for HL +1075C and minus -480T were 0.053 and 0.362, respectively and the prevalence of HL +1075C/C and -480T/T were 0.006 and 0.132, respectively. Overall, the normal HDL-C (> or = 35 mg/dl) subjects had a higher carrier frequency of HL +1075C than the low HDL-C (<35 mg/dl) subjects (0.108 vs 0.029, P=0.039). However, when tested separately, the carrier frequency of HL +1075C was not significantly different between normal and low HDL-C females (0.101 vs 0.083, P=0.843). In males, the normal HDL-C subjects had a higher carrier frequency of HL +1075C than the low HDL-C subjects (0.113 vs 0.018, P=0.026). No significant difference of frequencies of HL -480T genotypes -480T/T,-480C/T and -480C/C was found between normal and low HDL-C subjects. Among plasma TG, TC, HDL-C, apo AI, apo AII, apo B100, apo CII, Apo CIII and apoE, only HDL-C and apo AI were significantly different among the three genotypes +1075A/A,+1075A/C and +1075C/C in men (P=0.029 and 0.032). No association was found in women. Male subjects with CC had a higher HDL-C than those with AC (P=0.020) and AA (P=0.013), AC higher than AA (P=0.017). Male subjects with CC had a higher apo AI than AC (P=0.013) and AA (P=0.019), AC higher than AA (P=0.021). Although not so significant (P=0.053) as HDL-C and apo AI, male subjects with CC had a higher apo AII than those with AC and AA. No significant difference of lipoprotein and apolipoprotein traits was found among the three -480T genotypes -480C/C,-480C/T and -480T/T, in the sample overall and in men and women separately. These results indicate that HL +1075C, not -480T polymorphism is associated with plasma high density lipoprotein cholesterol and apolipoprotein AI in men in this Chinese population. |
| Polymorphism of POPE/cholesterol system: a 2H nuclear magnetic resonance and infrared spectroscopic investigation Pare, C. and M. Lafleur (1998), Biophys J 74(2 Pt 1): 899-909. Abstract: It is well established that cholesterol induces the formation of a liquid-ordered phase in phosphatidylcholine (PC) bilayers. The goal of this work is to examine the influence of cholesterol on phosphatidylethanolamine polymorphism. The behavior of 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE)/cholesterol mixtures was characterized using infrared and 2H nuclear magnetic resonance (NMR) spectroscopy (using POPE bearing a perdeuterated palmitoyl chain in the latter case). Our results reveal that cholesterol induces the formation of a liquid-ordered phase in POPE membranes, similar to those observed for various PC/cholesterol systems. However, the coexistence region of the gel and the liquid-ordered phases is different from that proposed for PC/cholesterol systems. The results indicate a progressive broadening of the gel-to-fluid phase transition, suggesting the absence of an eutectic. In addition, there is a progressive downshift of the end of the transition for cholesterol content higher than 10 mol %. Cholesterol has an ordering effect on the acyl chains of POPE, but it is less pronounced than for the PC equivalent. This study also shows that the cholesterol effect on the lamellar-to-hexagonal (L(alpha)-H(II)) phase transition is not monotonous. It shifts the transition toward the low temperatures between 0 and 30 mol % cholesterol but shifts it toward the high temperatures when cholesterol content is higher than 30 mol %. The change in conformational order of the lipid acyl chains, as probed by the shift of the symmetric methylene C-H stretching, shows concerted variations. Finally, we show that cholesterol maintains its chain ordering effect in the hexagonal phase. |
| Polymorphisms in ABCG5 and ABCG8 transporters and plasma cholesterol levels Hubacek, J. A., K. E. Berge, et al. (2004), Physiol Res 53(4): 395-401. Abstract: ABCG5 and ABCG8 transporters play an important role in the absorption and excretion of sterols. Missence polymorphisms (Gln604Glu in the ABCG5 and Asp19His, Tyr54Cys, Thr400Lys, and Ala632Val in the ABCG8) in these genes have been described. In 131 males and 154 females whose dietary composition markedly changed and lipid parameters decreased over an 8-year follow-up study (total cholesterol decreased from 6.21+/-1.31 mmol/l in 1988 to 5.43+/-1.06 mmol/l in 1996), these polymorphisms were investigated using PCR. Plasma lipid levels and changes in plasma lipid levels were independent of the Gln604Glu polymorphism in ABCG5 and Asp19His and the Ala632Val polymorphisms in ABCG8. The Tyr54Cys polymorphism influenced the degree of reduction in total plasma cholesterol (delta -0.49 mmol/l in Tyr54 homozygotes vs. delta +0.12 mmol/l in Cys54 homozygotes, p<0.04) and LDL-cholesterol (delta -0.57 mmol/l in Tyr54 homozygotes vs. delta +0.04 mmol/l in Cys54 homozygotes, p<0.03) levels between 1988 and 1996 in females, but not in males. Male Thr400 homozygotes exhibited a greater decrease in total cholesterol (delta -0.90 mmol/l vs. delta -0.30 mmol/l, p<0.02) and LDL-cholesterol (delta -0.62 mmol/l vs. delta -0.19 mmol/l, p<0.04) than Lys400 carriers. No such association was observed in females. We conclude that Tyr54Cys and Thr400Lys variations in the ABCG8 gene may play a role in the genetic determination of plasma cholesterol levels and could possibly influence the gender-specific response of plasma cholesterol levels after dietary changes. These polymorphisms are of potential interest as genetic variants that may influence the lipid profile. |
| Polymorphisms in genes for cholesterol ester transfer protein, apolipoprotein C-III and lipoprotein lipase in children with high and low cholesterol levels Hubacek, J. A., H. Pistulkova, et al. (2001), Cas Lek Cesk 140(3): 79-81. Abstract: BACKGROUND: High plasma lipids are one of the risk factor of atherosclerosis. The contribution of environmental and genetic factors to plasma lipids is roughly equal. Cholesterol ester transfer protein (CETP), lipoprotein lipase (LPL) and apolipoprotein (apo) CIII play an important role in plasma lipid metabolism. The aim of the study was to establish the role of polymorphisms in these genes in plasma lipid determination. METHODS AND RESULTS: Using PCR and restriction analysis we have measured Taq1 polymorphism in CETP, asparagine 291/serine polymorphism in LPL and C3238G polymorphism in apo CIII genes in two groups of children selected from opposite ends of the cholesterol distribution curve of 2000 children. 82 children in high- (HCG) and 86 in low- (LCG) cholesterol group participated in the study. No significant difference was found in the frequencies of the CETP and apo CIII genotypes between LCG and HCG. In the LCG, significantly more carriers (p < 0.05) of the LPL serine291 allele were found. CONCLUSIONS: Common polymorphisms in the CETP and apo CIII genes do not determine the plasma lipid levels in childhood. The carriers of the rare allele in the LPL gene could be genetically predisposed to low plasma lipid levels. |
| Polymorphisms in the ABCG5 and ABCG8 genes associate with cholesterol absorption and insulin sensitivity Gylling, H., M. Hallikainen, et al. (2004), J Lipid Res 45(9): 1660-5. Abstract: The roles of polymorphisms of the sitosterolemia genes ABCG5 and ABCG8 in the regulation of cholesterol metabolism and insulin sensitivity were studied in mildly hypercholesterolemic noncoronary subjects (n = 263, 144 men and 119 women) divided into tertiles by baseline serum cholestanol-to-cholesterol ratio (< or = 118.3 and > or = 147.7 10(2) x mmol/mol cholesterol), a surrogate marker of cholesterol absorption efficiency. The lowest cholestanol tertile was associated with high body mass index (BMI), plasma glucose, serum insulin and triglycerides, and cholesterol synthesis markers (cholestenol, desmosterol, lathosterol) and low HDL cholesterol and cholesterol absorption markers (campesterol, sitosterol) (P < 0.01 for all). The 19H allele of the ABCG8 gene accumulated in the lowest cholestanol tertile (P < 0.001) and was associated with low total and LDL cholesterol and absorption markers and with high synthesis markers (P < 0.05 for all). The 604E allele of the ABCG5 gene in men was associated with high BMI, plasma insulin, low serum sitosterol, and high serum cholestenol levels (P < 0.05 for all). In a subgroup of 71 men, the 604E allele was associated with insulin resistance measured with the hyperinsulinemic euglycemic clamp. In conclusion, low cholesterol absorption efficiency was associated with characteristics of the metabolic syndrome. Low serum cholesterol and cholesterol absorption were linked to the D19H polymorphism of the ABCG8 gene, and characteristics of the insulin resistance syndrome in men were linked with the Q604E polymorphism of the ABCG5 gene. |
| Polymorphisms in the gene coding for cholesteryl ester transfer protein are related to plasma high-density lipoprotein cholesterol and transfer protein activity Freeman, D. J., C. J. Packard, et al. (1990), Clin Sci (Lond) 79(6): 575-81. Abstract: 1. Cholesteryl ester transfer protein activity may have a physiological effect on high-density lipoprotein levels. 2. We examined restriction fragment length polymorphisms associated with the cholesteryl ester transfer protein gene and the apolipoprotein AI gene in a group of 60 unrelated subjects selected from an initial survey of 5000 subjects on the basis of their high-density lipoprotein levels being high or low at the extremes of the distribution. The activities of cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase (phosphatidylcholine-sterol acyltransferase, EC 2.3.1.43) were also determined. Analysis by selection of those with a low high-density lipoprotein cholesterol level (less than or equal to 1.1 for males, less than or equal to 1.2 for females) gave 32 individuals with 24% B2 alleles. Selection of subjects with a high-density lipoprotein cholesterol level (less than or equal to 2 mmol/l) gave 17 with 62% B2 alleles. 3. The group with low levels of high-density lipoprotein cholesterol had higher activity of cholesteryl ester transfer protein and significantly elevated triacylglycerol levels when compared with the group with high levels of high-density lipoprotein cholesterol. 4. A further significant finding was the correlation of the MspI restriction fragment length polymorphism detected by the apolipoprotein AI gene with lecithin:cholesterol acyltransferase activity. |
| Polymorphisms of the gene encoding cholesterol ester transfer protein and serum lipoprotein levels in subjects with and without coronary heart disease Tenkanen, H., P. Koshinen, et al. (1991), Hum Genet 87(5): 574-8. Abstract: We determined TaqI-A, TaqI-B and EcoNI genotypes at the cholesteryl ester transfer protein (CETP) locus in 111 healthy volunteers and in 187 hyperlipidemic men of whom 72 had suffered a myocardial infarction. There were no significant differences in the allele distributions at these polymorphic loci either between the population sample and the hyperlipidemic subjects, or between patients with and without previous myocardial infarction. To detect the associations between the CETP polymorphisms and serum lipid and apoprotein levels, we determined the serum concentrations of total cholesterol, triglycerides, high density lipoprotein (HDL)-cholesterol, apoA-I, apoA-II and apoB in the subjects studied and correlated them to the 3 RFLPs. No significant differences were observed in the serum levels of apoproteins and lipid parameters between subjects with different genotypes in any of these polymorphic CETP loci, either in the population sample or in hyperlipidemic men. Multivariate analyses did not reveal a significant independent role for any of the 3 polymorphisms in determining serum HDL-cholesterol or apoA-I levels after adjusting for triglyceride and low density lipoprotein cholesterol concentrations. This was evident for the group of healthy volunteers and for hyperlipidemic subjects, including those who had survived a myocardial infarction. We conclude that, in Finns, the CETP RFLPs are not useful markers for the risk of coronary heart disease. |
| Polymorphisms of the genes encoding apoproteins A-I, B, C-III, and E and LDL receptor, and cholesterol and LDL metabolism during increased cholesterol intake. Common alleles of the apoprotein E gene show the greatest regulatory impact Gylling, H., K. Kontula, et al. (1997), Arterioscler Thromb Vasc Biol 17(1): 38-44. Abstract: Genetic and dietary factors regulate serum cholesterol level, but detailed investigations into their interactions have not been established. We assessed the effects of apoprotein (apo) E phenotype and polymorphic alleles of the apo A-I, apo B, apo C-III, and LDL receptor genes, separately and together, on regulation of serum LDL cholesterol level. The study group consisted of 29 middle-aged men, and cholesterol absorption, bile acid, and cholesterol synthesis and LDL apo B kinetics were studied in these men during low- and high-cholesterol diets. The six apo B alleles were identified on the basis of Xba I, EcoRI, and Msp I restriction fragment length polymorphism (RFLP), the apo A-I alleles with the Msp I RFLP, and the apo C-III and LDL receptor alleles corresponded to the Sst I and PvuII RPLPs of these genes, respectively. During low cholesterol intake, LDL cholesterol levels were similar in all of the genetic groups except for men with apo E2 phenotype. They had significantly (P <.05) lower levels of LDL apo B and cholesterol than men without the epsilon 2 allele. The low values were caused by a significantly higher removal of LDL apo B (apo E2, 0.453 +/- 0.03 versus apo E3, 0.312 +/- 0.01 pools per day, P <.05). High cholesterol intake increased LDL cholesterol levels in all genetic categories except in the apo E2 phenotype irrespective of the combinations with other polymorphisms. Carriers of the apo B R+ allele (EcoRI site present) presented with the most prominent LDL cholesterol rise (from 2.71 +/- 0.14 to 3.37 +/- 0.29 mmol/L). In multiple stepwise regression analysis, apo B EcoRI RFLP and apo E phenotypes were the only variables that explained the variability of high cholesterol intake-induced change in LDL cholesterol levels. In summary, in any genetic combination, individuals with the epsilon 2 allele had the lowest LDL cholesterol values and were nonresponders to dietary cholesterol, whereas subjects with the apo B R+ allele had marked LDL elevations, especially in combination with the epsilon 4. |
| Polymorphisms of the HDL receptor gene associated with HDL cholesterol levels in diabetic kindred from three populations McCarthy, J. J., S. Lewitzky, et al. (2003), Hum Hered 55(4): 163-70. Abstract: OBJECTIVE: We examined polymorphisms in the HDL receptor, SR-BI, for association with plasma HDL cholesterol levels. METHODS: Study subjects, including 847 women and 725 men, were from families originally ascertained for type 2 diabetes from Finland, Sweden and Israel. Four common polymorphisms were examined in linear regression analysis: an exon 1 missense (EX1), exon 8 silent (EX8), intron 5 (IVS5) and intron 10 (IVS10) variants. RESULTS: Genotype combinations for the three polymorphisms in linkage disequilibrium (IVS5, EX8 and IVS10) were found to be associated with HDL-C among women from the Israeli (p = 0.01) and Swedish (p = 0.06) populations. In Finnish women, the association was only apparent after taking into account effect modification by triglyceride levels (p = 0.04). One specific pattern of genotypes, denoted by presence of the IVS5_T and EX8_C alleles, and absence of the IVS10_G allele, was consistently associated with the lowest mean levels of HDL-C in women from all three populations. These same associations were not found in men. CONCLUSIONS: Polymorphic variation of the SR-BI gene may influence HDL-C levels and act in a sex-dependent manner. |
| Polyunsaturated and monounsaturated fatty acids in the diet to prevent coronary heart disease via cholesterol reduction Heyden, S. (1994), Ann Nutr Metab 38(3): 117-22. Abstract: For over 30 years the American Heart Association recommended to limit the fat intake to 30 energy % (E%) of total calories with 10 E% derived from polyunsaturated fatty acids (PUFA), 10 E% from monounsaturated fatty acids (MUFA) and 10 E% from saturated fatty acids (SFA). In 1988 and subsequent years, the National Cholesterol Education Program has changed this advise in favor of an increase of 15 E% MUFA and a reduction to 5 E% PUFA. This dramatic change was based largely on short-term dietary experiments, with formula diets with small numbers of subjects, and anecdotal epidemiological evidence from the population of Crete. The assertion that oleic acid may lower cholesterol and LDL remains unproven. However, isocaloric substitution of linoleic acid for oleic acid lowers cholesterol and LDL. Oleic acid has little or no effect on lipids and lipoproteins except as it replaces SFA. Large dietary feeding experiments in the 1950s and 1960s with persons with hypercholesterolemia and with patients after myocardial infarction were conducted with PUFA-enriched diets and proved effective in primary and secondary prevention of coronary heart disease. No such studies exist with MUFA-enriched diets. Therefore, the original recommendations remain the standard of dietary advise to healthy persons and patients after myocardial infarction. |
| Polyunsaturated fatty acids modulate the effects of the APOA1 G-A polymorphism on HDL-cholesterol concentrations in a sex-specific manner: the Framingham Study Ordovas, J. M., D. Corella, et al. (2002), Am J Clin Nutr 75(1): 38-46. Abstract: BACKGROUND: A common G-to-A substitution in the promoter area (-75 base pairs) of the apolipoprotein A-I gene (APOA1) has been described. The A allele was shown to be associated with higher HDL-cholesterol concentrations in some studies but not in others. OBJECTIVE: We examined whether dietary fat modulates the association between this polymorphism and HDL-cholesterol concentrations. DESIGN: We studied a population-based sample of 755 men and 822 women from the Framingham Offspring Study. RESULTS: The frequency of the A allele was 0.165. No significant differences were observed between G/G subjects and carriers of the A allele for any lipid variables. In multivariate linear regression models, HDL-cholesterol concentrations in women were associated with a significant interaction between polyunsaturated fatty acid (PUFA) intake as a continuous variable and APOA1 genotype (P = 0.005). By using 3 categories of PUFA intake, we found a significantly different effect of APOA1 genotype across PUFA categories in women. When PUFA intake was <4% of energy, G/G subjects had approximately 14% higher HDL-cholesterol concentrations than did carriers of the A allele (P < 0.05). Conversely, when PUFA intake was >8%, HDL-cholesterol concentrations in carriers of the A allele were 13% higher than those of G/G subjects (P < 0.05). No significant allelic difference was observed for subjects in the range of PUFA intake of 4-8% of energy. These interactions were not significant in men. CONCLUSIONS: We found a significant gene-diet interaction associated with the APOA1 G-A polymorphism. In women carriers of the A allele, higher PUFA intakes were associated with higher HDL-cholesterol concentrations, whereas the opposite effect was observed in G/G women. |
| Polyunsaturated fatty acids result in greater cholesterol lowering and less triacylglycerol elevation than do monounsaturated fatty acids in a dose-response comparison in a multiracial study group Howard, B. V., J. S. Hannah, et al. (1995), Am J Clin Nutr 62(2): 392-402. Abstract: Cholesterol-lowering effects of polyunsaturated and monounsaturated fatty acids were compared as they were varied in a reciprocal dose-dependent fashion in the context of a National Cholesterol Education Program (NCEP) Step 1 diet. The study population comprised 63 moderately hypercholesterolemic African American and white men and women. After a 6-wk baseline diet containing 37% of energy from total fat and 15% from saturated fat, participants consumed four diets for 6 wk each, in random order, containing 10% of energy as saturated fatty acids; 3%, 6%, 10%, and 14% of energy as polyunsaturated fatty acids; and 17%, 14%, 10%, and 6% of energy as monounsaturated fatty acids. Dietary cholesterol, fiber, plant sterol, and squalene contents were constant with all four diets. There was a progressive decrease in total (P = 0.028) and low-density-lipoprotein cholesterol (P = 0.184) across the four diets, with the greatest decrease observed in the diet with the highest content of polyunsaturated fatty acids; a small but significant decrease in high-density-lipoprotein (HDL) cholesterol that did not show a trend between the polyunsaturated and monounsaturated diets; and a trend between the four diets in triacylglycerol elevations (P = 0.029), with the smallest increment occurring in the diets highest in polyunsaturates. The magnitude of the cholesterol-lowering response was greater in those with higher baseline cholesterol and less in those who were more obese. The dietary response was similar in both ethnic groups and in both sexes. In conclusion, in an NCEP Step 1 diet containing 30% total fat, with all other known cholesterol-influencing dietary factors held constant, the substitution of polyunsaturated fatty acid for monounsaturated fatty acid from 3% to 14% resulted in a progressive decline in total cholesterol and less triacylglycerol elevations, without effect on HDL cholesterol. |
| Pomegranate juice supplementation to atherosclerotic mice reduces macrophage lipid peroxidation, cellular cholesterol accumulation and development of atherosclerosis Kaplan, M., T. Hayek, et al. (2001), J Nutr 131(8): 2082-9. Abstract: Inhibition of lipid peroxidation contributes to the attenuation of macrophage cholesterol accumulation, foam-cell formation and atherosclerosis. Evidence suggests that nutritional antioxidants such as pomegranate juice (PJ) can contribute to the reduction of oxidative stress and atherogenesis. The goals of the present study were to determine whether such beneficial effects of PJ exist when supplemented to apolipoprotein E-deficient (E(0)) mice with advanced atherosclerosis and to analyze the antiatherosclerotic activity of a tannin-fraction isolated from PJ. Mice (4-mo-old) were supplemented with PJ in their drinking water for 2 mo and compared with age-matched placebo-treated mice, as well as to young (4-mo-old) control mice, for their mouse peritoneal macrophage (MPM) oxidative state, cholesterol flux and mice atherosclerotic lesion size. PJ supplementation reduced each of the proatherogenic variables determined in the present study compared with age-matched placebo-treated mice. It significantly induced serum paraoxonase activity and reduced MPM lipid peroxide content compared with placebo-treated mice and control mice. PJ administration to E(0) mice significantly reduced the oxidized (Ox)-LDL MPM uptake by 31% and MPM cholesterol esterification and increased macrophage cholesterol efflux by 39% compared with age-matched, placebo-treated mice. PJ consumption reduced macrophage Ox-LDL uptake and cholesterol esterification to levels lower than those in 4-mo-old, unsupplemented controls. PJ supplementation to E(0) mice with advanced atherosclerosis reduced the lesion size by 17% compared with placebo-treated mice. In a separate study, supplementation of young (2-mo-old) E(0) mice for 2 mo with a tannin fraction isolated from PJ reduced their atherosclerotic lesion size, paralleled by reduced plasma lipid peroxidation and decreased Ox-LDL MPM uptake. PJ supplementation to mice with advanced atherosclerosis reduced their macrophage oxidative stress, their macrophage cholesterol flux and even attenuated the development of atherosclerosis. Moreover, a tannin-fraction isolated from PJ had a significant antiatherosclerotic activity. |
| Pool size and concentration of plasma cholesterol are increased and tissue copper levels are reduced during early stages of copper deficiency in rats al-Othman, A. A., F. Rosenstein, et al. (1994), J Nutr 124(5): 628-35. Abstract: The progressive development of hypercholesterolemia, enlargement of plasma cholesterol pool size, and alteration in tissue mineral concentrations were determined during the early stages of copper deficiency. Fifty-four weanling male Sprague-Dawley rats were assigned to three dietary Cu treatments: deficient (0.6 micrograms Cu/g diet), marginal (1.6 micrograms Cu/g diet) and adequate (6.6 micrograms Cu/g diet). Six rats from each treatment were killed after 3, 5 and 7 wk of dietary treatment. After only 3 wk of treatment, significantly lower hematocrits and liver Cu concentrations, as well as enlargements of plasma volume, plasma pool size of cholesterol and triacylglycerols and relative heart weight, were evident in rats fed the Cu-deficient and Cu-marginal diets relative to those fed the Cu-adequate diet. In general, these alterations were more pronounced in rats fed the Cu-deficient diet than in rats fed the Cu-marginal diet. Thereafter, the hematocrits and plasma volumes remained relatively constant, but the liver Cu concentration progressively decreased in rats in all treatments throughout the study. In contrast, the enlargements in plasma pool size of cholesterol and triacylglycerols relative to Cu-adequate rats were greater at the end of the study for the Cu-marginal and Cu-deficient rats. Most importantly, in the Cu-marginal rats, significantly greater plasma cholesterol and triacylglycerol pool sizes were detected earlier than were differences in concentrations. Thus, the present study established plasma cholesterol and triacylglycerol pool sizes as superior indices for the early detection of alterations in lipid metabolism in Cu deficiency. |
| Poor applicability of the Friedewald formula in the assessment of serum LDL cholesterol for clinical purposes Marniemi, J., J. Maki, et al. (1995), Clin Biochem 28(3): 285-9. Abstract: OBJECTIVE: To determine the accuracy of the estimation of serum low-density lipoprotein (LDL) cholesterol concentration by the Friedewald formula. METHODS: Modifications of the calculation formula are presented on the basis of ultracentrifugal separation of serum high-density lipoprotein and LDL cholesterol in the specimens collected (n = 1215) in a nationwide health survey. RESULTS: The formulas obtained from different subject groups differed relatively little from each other. The accuracy of the original Friedewald formula was poor; in about 36% of the subjects the error was more than 5% compared with ultracentrifugally obtained results. By applying the currently recommended coronary heart disease (CHD) risk categorizations, high proportions (5%-28%) of the subjects were classified into wrong CHD risk categories when LDL cholesterol was calculated with any of the formulas. At high serum triglyceride levels, misclassifications were especially common. CONCLUSIONS: We conclude that even the most accurate LDL cholesterol calculation methods should be used with caution while classifying subjects into categories of CHD risk. In hypertriglyceridemic subjects, the calculation formulas probably should not be used at all. |