| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Genetic epidemiology of differences in low-density lipoprotein (LDL) cholesterol concentration: possible involvement of variation at the apolipoprotein B gene locus in LDL kinetics Houlston, R. S., P. R. Turner, et al. (1990), Genet Epidemiol 7(3): 199-210. Abstract: Circulating levels of low-density lipoprotein (LDL) vary considerably within and between populations, paralleled by differing coronary heart disease (CHD) mortality rates. We have previously shown that variation in the apolipoprotein (apo) B gene as associated with certain restriction fragment length polymorphisms (RFLPs) influences the metabolism of LDL in the U.K. population. To investigate a possible genetic contribution to variation in LDL levels in differing populations we have extended this original study. RFLPs of the apo B gene were determined in samples of individuals from the United Kingdom, Finland, Italy, Spain, and Africa. Significant associations of LDL fractional catabolic rate with the apo B EcoRI and XbaI RFLP genotypes were detected only in the two North European populations. In the African population sample, the XbaI RFLP displayed a significant association with LDL apo B synthesis. The data suggest that variation in the apo B gene influences the metabolism of LDL and that it is different in individuals of different ethnic background. |
| Genetic factors affecting the consistency and magnitude of changes in plasma cholesterol in response to dietary challenge Humphries, S. E., P. J. Talmud, et al. (1996), Qjm 89(9): 671-80. Abstract: We examined the role of common genetic variation in determining the consistency and magnitude of change in plasma total cholesterol (TC) levels in response to two separate changes from a high-saturated (SFA) to a low-saturated/high-polyunsaturated-fat (PUFA) diet, in a group of free-living healthy men and women. Consistent responders were defined as those whose mean difference in the change in TC was within one SD of the mean for all participants, and the remainder were defined as variable responders. DNA was obtained from 55 individuals and genotype determined at the apolipoprotein (apo) B locus (signal peptide, SP), apoCIII (C1100-T) and lipoprotein lipase (LPL) gene loci (HindIII). In the 38 consistent responders, the apoBSP24 allele was significantly more common than in the 17 individuals with a variable response (0.29 vs. 0.12; p < 0.05). No other polymorphism showed a significant frequency difference between groups. In the group as a whole, the correlation between the change in TC level in response to the first and second dietary change was 0.28 (p = 0.05), but those with one or more apoB SP24 alleles and those with the apoCIII genotype CC had a significantly higher correlation than those with other genotypes (0.46 (p = 0.05) vs. 0.12 (NS) and 0.31 (p = 0.05) vs. 0.02 (NS), respectively). In the group as a whole, mean response left TC 10% higher on the SFA than on the PUFA diet, and neither apoB nor apoCIII genotypes affected the magnitude of this response. However, individuals with the LPL HindIII genotype H+ H+ had a significantly smaller change in mean TC in response to diet than those with one or more H- allele (9.3% vs. 14.4%; p = 0.03). Thus variation at the apoB and apoCIII loci affects the consistency of response to change in dietary fat content, while variation at the LPL gene locus affects magnitude of response. |
| Genetic factors at the enterocyte level account for variations in intestinal cholesterol absorption efficiency among inbred strains of mice Wang, D. Q., B. Paigen, et al. (2001), J Lipid Res 42(11): 1820-30. Abstract: Interindividual and interstrain variations in cholesterol absorption efficiency occur in humans and animals. We investigated physiological biliary and small intestinal factors that might determine variations in cholesterol absorption efficiency among inbred mouse strains. We found that there were significant differences in cholesterol absorption efficiency measured by plasma, fecal, and lymphatic methods: <25% in AKR/J, C3H/J, and A/J strains; 25-30% in SJL/J, DBA/2J, BALB/cJ, SWR/J, and SM/J strains; and 31-40% in C57L/J, C57BL/6J, FVB/J, and 129/SvJ strains. In (AKRxC57L)F1 mice, the cholesterol absorption efficiency (31 +/- 6%) mimicked that of the C57L parent (37 +/- 5%) and was significantly higher than in AKR mice (24 +/- 4%). Although biliary bile salt compositions and small intestinal transit times were similar, C57L mice displayed significantly greater bile salt secretion rates and pool sizes than AKR mice. In examining lymphatic cholesterol transport in the setting of a chronic biliary fistula, C57L mice displayed significantly higher cholesterol absorption rates compared with AKR mice. Because biliary and intestinal transit factors were accounted for, we conclude that genetic variations at the enterocyte level determine differences in murine cholesterol absorption efficiency, with high cholesterol absorption likely to be a dominant trait. This study provides baseline information for identifying candidate genes that regulate intestinal cholesterol absorption at the cellular level. |
| Genetic factors influence the atherogenic response of lipoproteins to dietary fat and cholesterol in nonhuman primates Rudel, L. L. (1997), J Am Coll Nutr 16(4): 306-12. Abstract: Comparative studies of diet responsiveness have carried out in five different old world primate species, including African green, stumptail, rhesus, patas, and cynomolgus monkeys. The dietary variables examined were level of cholesterol (0.03 and 0.8 mg cholesterol/kcal) and type of fat (enriched in saturated vs. n-6 polyunsaturated fatty acids). In all cases, hypercholesterolemia resulted from the high cholesterol diet, making it possible to identify low, moderate, and high responding species. Polyunsaturated vs. saturated fat effects to lower plasma cholesterol did not appear to be remarkably species specific, except for the more pronounced response in African green monkeys. For low-density lipoprotein (LDL) cholesterol concentrations, African green monkeys were the lowest responding species and cynomolgus monkeys were the highest. LDL particle enlargement was least in African green monkeys and highest in rhesus and cynomolgus monkeys. High-density lipoprotein (HDL) cholesterol levels were similar among species on the low cholesterol diet, but decreased when the high cholesterol diet was fed in all species except African green monkeys, where HDL increased with added dietary cholesterol. Coronary artery atherosclerosis developed only when the high cholesterol diet was fed, occurred more rapidly, and became more extensive in cynomolgus compared to African green monkeys. Polyunsaturated fat limited the amount of atherosclerosis that developed in both species. Genetic factors regulating the response to dietary cholesterol in degree of hyperlipoproteinemia, cholesterol distribution among lipoproteins, LDL particle size, and HDL cholesterol concentration were characteristically unique among different primate species. The effects of lipoproteins were well correlated with the extent of coronary artery atherosclerosis. |
| Genetic factors that contribute to interindividual variations in plasma low density lipoprotein-cholesterol levels Cohen, J., A. Gaw, et al. (1996), Ciba Found Symp 197: 194-206; discussion 206-10. Abstract: The interplay of multiple genes and environmental factors generates interindividual variation in plasma low density lipoprotein-cholesterol (LDL-C) concentrations. As a result, it has been difficult to identify individual genes that contribute to variation in plasma LDL-C levels using classical linkage analysis. We have exploited a genetic defect in the gene encoding the LDL receptor that is associated with a dramatically elevated plasma LDL-C level to unmask an allele at another locus that lowers plasma LDL-C levels. The existence of such an allele was implied by the analysis of a human pedigree with familial hypercholesterolaemia in which a third of the familial hypercholesterolaemia heterozygotes had normal levels of LDL-C. To develop an animal model of this LDL-C lowering effect and to identify genes that modify the plasma LDL-C level, we crossed LDL receptor-deficient mice with other strains of mice. |
| Genetic influence on HDL cholesterol Betteridge, D. J. and M. Kahn (1998), Lancet 351(9120): 1903-4. |
| Genetic influences on age-related change in total cholesterol, low density lipoprotein-cholesterol, and triglyceride levels: longitudinal apolipoprotein E genotype effects Jarvik, G. P., M. A. Austin, et al. (1994), Genet Epidemiol 11(4): 375-84. Abstract: This study addressed the possible influence of apolipoprotein E (apo E) genotype on age-related changes in total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), and triglyceride (TG) levels in older males. Apo E is a component of LDL, is a ligand for the LDL receptor, and apo E genotype has been consistently associated with variation in mean levels of TC and LDL-C, and also appears to influence TG levels. Using male twins followed longitudinally between mean ages of 48 and 63 years, the change in TC, LDL-C, and TG over time for individuals with the epsilon 3 epsilon 3 and the epsilon 3 epsilon 4 genotypes was contrasted. At exam 1 mean TC and LDL-C levels were lower in the epsilon 3 epsilon 3 group than in the epsilon 3 epsilon 4 group, but at exam 3 mean TC and LDL-C levels were significantly higher in the epsilon 3 epsilon 3 group than in the epsilon 3 epsilon 4 group. The rate of change in TC and LDL-C with age differed significantly between epsilon 3 epsilon 3 and epsilon 3 epsilon 4 groups. Results for TG were not statistically significantly. These findings suggest that the apo E genotype effects on risk of coronary artery disease may be age-dependent. This study demonstrates the value of longitudinal studies in refining models for genetic risk factors for disease. |
| Genetic lipoprotein abnormalities producing high blood cholesterol Brown, W. V. and J. L. Breslow (1992), Heart Dis Stroke 1(6): 405-7. |
| Genetic markers associated with high density lipoprotein cholesterol levels in a biracial population sample Anderson, R. A., T. L. Burns, et al. (1992), Genet Epidemiol 9(2): 109-21. Abstract: An explanation for the consistently documented finding of higher levels of high density lipoprotein-cholesterol in black men relative to white men was sought by comparing the frequency of restriction fragment length polymorphism markers present in blacks and in whites at the gene loci coding for the two major apolipoprotein constituents of high density lipoprotein, apolipoproteins AI and AII. The measurements were made in population-based samples of 45 to 54-year-old black (n = 190) and white (n = 370) subjects from the Minnesota Heart Survey for whom lipoprotein levels were available. The mean high density lipoprotein-cholesterol level for black men in the sample (47 +/- 1.5 mg/dl) was higher (P less than 0.05) than that for white men (42 +/- 0.9 mg/dl), while levels in women were not different between races. While the SacI and MspI markers at the apolipoprotein AI-CIII-AIV gene locus showed similar frequencies in blacks compared to whites, the degree of the linkage disequilibrium previously noted between these markers in white subjects was altered in blacks and the minor allele of the PstI marker at this locus was virtually absent in the black subjects (P less than 0.005 vs whites). For black men, there were significant associations of the M2 allele and the S2M2 haplotype at the apolipoprotein AI locus with lower high density lipoprotein-cholesterol levels. The results are consistent with the hypothesis that DNA sequence variations in the vicinity of the apolipoprotein AI-CIII-AIV gene locus are associated with the difference in high density lipoprotein-cholesterol levels between blacks and whites. |
| Genetic polymorphisms and activity of cholesterol ester transfer protein (CETP): should we be measuring them? Ordovas, J. M. (2000), Clin Chem Lab Med 38(10): 945-9. Abstract: Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that mediates the transfer of cholesteryl ester from high density lipoproteins (HDL) to triglyceride-rich lipoproteins in exchange for triglycerides. Several approaches are currently being used in research laboratories to measure its activity and/or mass. However, these assays are not standardized and it is not possible to compare data from different laboratories. Also, we lack enough information to assess the value of this variable as a coronary heart disease (CHD) predictor. Several genetic variants at CETP locus have been identified and they have been generally associated with increased HDL-cholesterol concentrations. However, there is no consensus about the association of this CETP-related increase in HDL-cholesterol and protection against CHD. Nevertheless, the most recent evidence from the common CETP-TaqI-B polymorphism shows that the lower CETP activity associated with the presence of this polymorphism decreases CHD risk in men. Based on this and previous evidence, there has been an interest in the development of CETP inhibitors as a tool to increase HOL-cholesterol, thus reducing CHD risk. However, it should be noted that the evidence about the cardioprotective role of these drugs is not yet available. |
| Genetic regulation of cholesterol absorption and plasma plant sterol levels: commonalities and differences Sehayek, E. (2003), J Lipid Res 44(11): 2030-8. Abstract: The molecular basis of the processes that control two closely related traits, the absorption of cholesterol from the intestines and plasma plant sterol levels, are only partially understood. The discovery that mutations in two novel hemitransporters, ATP binding cassette transporter G5 (ABCG5) and ABCG8, underlie a rare inborn error in plant sterol metabolism, beta-sitosterolemia, represents a major breakthrough in this field. More recently, genetic studies in the mouse that mapped loci in linkage with cholesterol absorption and plasma plant sterol levels and studies in humans that examined the relationship of plasma plant sterol levels to sequence variation in the ABCG5/ABCG8 locus suggested the involvement of other genes. Moreover, studies in beta-sitosterolemic patients, in ABCG5/ABCG8-targeted animals, and on a newly developed cholesterol absorption inhibitor, ezetimibe, suggest commonalities and differences in the regulation of the two traits. This review summarizes the evidence for genetic control of cholesterol absorption and plasma plant sterol levels, presents the evidence for commonalities and differences between the two traits, and discusses recent developments and future perspectives in this field. |
| Genetic regulation of cholesterol homeostasis: chromosomal organization of candidate genes Welch, C. L., Y. R. Xia, et al. (1996), J Lipid Res 37(7): 1406-21. Abstract: As part of an effort to dissect the genetic factors involved in cholesterol homeostasis in the mouse model, we report the mapping of 12 new candidate genes using linkage analysis. The genes include: cytoplasmic HMG-CoA synthase (Hmgcs 1, Chr 13), mitochondrial synthase (Hmgcs 2, Chr 3), a synthase-related sequence (Hmgcs 1-rs, Chr 12), mevalonate kinase (Mvk, Chr 5), farnesyl diphosphate synthase (Fdps, Chr 3), squalene synthase (Fdft 1, Chr 14), acyl-CoA:cholesterol acyltransferase (Acact, Chr 1), sterol regulatory element binding protein-1 (Srebf1, Chr 8) and -2 (Srebf2, Chr 15), apolipoprotein A-I regulatory protein (Tcfcoup2, Chr 7), low density receptor-related protein-related sequence (Lrp-rs, Chr 10), and Lrp-associated protein (Lrpap 1, Chr 5). In addition, the map positions for several lipoprotein receptor genes were refined. These genes include: low density lipoprotein receptor (Ldlr, Chr 9), very low density lipoprotein receptor (Vldlr, Chr 19), and glycoprotein 330 (Gp330, Chr 2). Some of these candidate genes are located within previously defined chromosomal regions (quantitative trait loci, QTLs) contributing to plasma lipoprotein levels, and Acact maps near a mouse mutation, ald, resulting in depletion of cholesteryl esters in the adrenals. The combined use of QTL and candidate gene mapping provides a powerful means of dissecting complex traits such as cholesterol homeostasis. |
| Genetic screening of the lipoprotein lipase gene for mutations associated with high triglyceride/low HDL-cholesterol levels Razzaghi, H., C. E. Aston, et al. (2000), Hum Genet 107(3): 257-67. Abstract: The lipoprotein lipase (LPL) enzyme plays a major role in lipid metabolism, primarily by regulating the catabolism of triglyceride (TG)-rich lipoprotein particles. The gene for LPL is an important candidate for affecting the risk of atherlosclerosis in the general population. Previously, we have shown that the HindIII polymorphism in intron 8 of the LPL gene is associated with plasma TG and HDL-cholesterol variation in Hispanics and non-Hispanic whites (NHWs). However, this polymorphism is located in an intron and hence may be in linkage disequilibrium with a functional mutation in the coding region or intron-exon junctions of the LPL gene. The aim of this study was to initially screen the LPL coding region and the intron-exon junctions by single-strand conformation polymorphism (SSCP) analysis for mutation detection in a group of 86 individuals expressing the phenotype of high TG/low HDL, followed by association studies in a population-based sample of 1,014 Hispanics and NHWs. Four sequence variations were identified by SSCP and DNA sequencing in the coding region of the gene, including two missense mutations (D9N in exon 2 and N291S in exon 6), one samesense mutation (V108V in exon 3), and one nonsense mutation (S447X in exon 9). Multiple regression analyses, including these four mutations and the HindIII polymorphic site, indicate that the association of the HindIII site with plasma TG (P=0.001 in NHWs and P=0.002 in Hispanics) and HDL-cholesterol (P=0.007 in NHWs and P=0.127 in Hispanics) is independent of all other LPL variable sites examined. These observations reinforce the concept that the intronic 8 HindIII site is functional by itself and provide a strong rationale for future comprehensive functional studies to delineate its biological significance. |
| Genetic studies of human apolipoproteins. XVI. APOE polymorphism and cholesterol levels in the Mayans of the Yucatan Peninsula, Mexico Kamboh, M. I., K. M. Weiss, et al. (1991), Clin Genet 39(1): 26-32. Abstract: Structural variation at the APOE locus is a major determinant of interindividual differences in cholesterol levels in populations at large. We have determined APOE structural polymorphism and estimated its impact on total cholesterol in the Mayans of the Yucatan Peninsula from Mexico. A unique pattern of APOE allele frequency distribution was observed, with no example of the APOE*2 allele and a relatively low incidence (9%) of the APOE*4 allele, giving rise to the lowest average heterozygosity at the APOE locus observed to date. The reported elevating affect of the APOE*4 allele on cholesterol has been found to be absent in the Mayans; several possible explanations which may account for the absence of this affect are discussed. In addition to APOE the gene products of five other apolipoprotein loci were screened and low frequency variation, possibly due to European admixture, was observed in two systems (APOH and APOA-IV). |
| Genetic variance and heritability of serum cholesterol and triglycerides among Chinese twin neonates Chen, C. J., M. W. Yu, et al. (1990), Acta Genet Med Gemellol (Roma) 39(1): 123-31. Abstract: In order to examine the genetic variance and heritability of serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides, a total of 349 pairs of same-sexed twin neonates born in four major general teaching hospitals in Taipei City were studied. Based on the placental pattern and 12 red blood cell antigens, 271 monozygotic (MZ) and 78 dizygotic (DZ) twin pairs were identified. There was a significant genetic variance for total cholesterol, HDL-C, LDL-C, and triglycerides both unadjusted and adjusted for sex, gestational age and placentation. The unadjusted heritability of total cholesterol, HDL-C, LDL-C, and triglycerides was 0.59, 0.30, 0.25 and 0.75, respectively; while the corresponding adjusted heritability was 0.74, 0.38, 0.31, and 0.49, respectively. Intrapair variance of serum lipids was not significantly different between monochorionic and dichorionic MZ twins. |
| Genetic variant showing a positive interaction with beta-blocking agents with a beneficial influence on lipoprotein lipase activity, HDL cholesterol, and triglyceride levels in coronary artery disease patients. The Ser447-stop substitution in the lipoprotein lipase gene. REGRESS Study Group Groenemeijer, B. E., M. D. Hallman, et al. (1997), Circulation 95(12): 2628-35. Abstract: BACKGROUND: Lipoprotein lipase (LPL) is the rate-limiting enzyme in the lipolysis of triglyceride-rich lipoproteins, and the gene coding for LPL is therefore a candidate gene in atherogenesis. We previously demonstrated that two amino acid substitutions in LPL, the Asn291-Ser and the Asp9-Asn, are associated with elevated triglycerides and lower HDL cholesterol and are present with greater frequency in coronary artery disease (CAD) patients than in normolipidemic control subjects. Conversely, a third frequent mutation in this gene, the Ser447-Stop, is reported by some investigators to underlie higher HDL cholesterol levels and would represent a beneficial genetic variant in lipoprotein metabolism. We therefore sought conclusive evidence for these allegations by investigating the effects of the LPL Ser447-Stop mutation on LPL and hepatic lipase (HL) activity, HDL cholesterol, and triglycerides in a large group of CAD patients (n = 820) with normal to mildly elevated total and LDL cholesterol levels. METHODS AND RESULTS: Carriers of the Ser447-Stop allele (heterozygotes and homozygotes) had significantly higher postheparin LPL activity (P =.034), normal postheparin HL activity (P =.453), higher HDL cholesterol levels (P =.013), and lower triglyceride levels (P =.044) than noncarriers. The influence of the Ser447-Stop allele on LPL activity was pronounced in patients using beta-blockers (P =.042) and not significant in those not using them (P =.881), suggesting a gene-environment interaction between the Ser447-Stop mutation and beta-blockers. CONCLUSIONS: We conclude that the LPL Ser447-Stop mutation has a significant positive effect on LPL activity and HDL cholesterol and triglyceride levels and that certain subgroups of CAD patients carrying the Ser447-Stop mutation will have less adverse metabolic effects when placed on beta-blockers. The LPL Ser447-Stop mutation therefore should have a protective effect against the development of atherosclerosis and subsequent CAD. |
| Genetic variants in PCSK9 affect the cholesterol level in Japanese Shioji, K., T. Mannami, et al. (2004), J Hum Genet 49(2): 109-14. Abstract: Mutations in the proprotein convertase subtilisin/kexin 9 (PCSK9) gene have been reported in affected members of two families with autosomal dominant hypercholesterolemia. To investigate the effects of common variants in PCSK9 on the cholesterol level, we conducted an association study using a large cohort representing the general population in Japan (n=1,793). Direct sequencing in all of the exonic regions identified 21 polymorphisms. After consideration of linkage disequilibrium among these polymorphisms, we selected and genotyped nine polymorphisms by the TaqMan method. The intron 1/C(-161)T and exon 9/I474 V polymorphisms were associated with levels of total cholesterol (TC) C(-161)T, P=0.0285; I474 V, P=0.0069 and low-density lipoprotein cholesterol (LDL-C) C(-161)T, P=0.0257; I474 V, P=0.0007. The distributions of these polymorphisms in subjects with miocardial infarction (MI) (n=649) were not different from those in the control population. These results provide the first evidence that common variants intron 1/C(-161)T and exon 9/I474 V in PCSK9 significantly affect TC and LDL-C levels in the general population in Japan. |
| Genetic variation in ABC transporter A1 contributes to HDL cholesterol in the general population Frikke-Schmidt, R., B. G. Nordestgaard, et al. (2004), J Clin Invest 114(9): 1343-53. Abstract: Homozygosity for mutations in ABC transporter A1 (ABCA1) causes Tangier disease, a rare HDL-deficiency syndrome. Whether heterozygosity for genetic variation in ABCA1 also contributes to HDL cholesterol (HDL-C) levels in the general population is presently unclear. We determined whether mutations or single-nucleotide polymorphisms (SNPs) in ABCA1 were overrepresented in individuals with the lowest 1% (n=95) or highest 1% (n=95) HDL-C levels in the general population by screening the core promoter and coding region of ABCA1. For all nonsynonymous SNPs identified, we determined the effect of genotype on lipid traits in 9,259 individuals from the general population. Heterozygosity for ABCA1 mutations was identified in 10% of individuals with low HDL-C only. Three of 6 nonsynonymous SNPs (V771M, V825I, and R1587K) were associated with increases or decreases in HDL-C in women in the general population and some with consistent trends in men, determined as isolated single-site effects varying only at the relevant SNP. Finally, these results were consistent over time. In conclusion, we show that at least 10% of individuals with low HDL-C in the general population are heterozygous for mutations in ABCA1 and that both mutations and SNPs in ABCA1 contribute to HDL-C levels in the general population. |
| Genetic variation in aldehyde dehydrogenase 2 and the effect of alcohol consumption on cholesterol levels Nakamura, Y., K. Amamoto, et al. (2002), Atherosclerosis 164(1): 171-7. Abstract: Moderate drinkers with a defective alcohol dehydrogenase type 3 (ADH3) genotype have higher high-density lipoprotein (HDL) levels and a decreased risk of coronary artery disease (CAD). We examined the interaction between the aldehyde dehydrogenase type 2 (ALDH2), alcohol intake, and HDL levels in 826 men and 1295 women in a rural town in Japan. The ALDH2 genotype of each subject was determined by polymerase chain reaction (PCR) analysis. HDL was adjusted for the alcohol intake, age, body mass index, smoking status, total cholesterol, triglycerides and HbA1c levels. None of the subjects had a history or ECG suggestive of CAD. The proportions of ALDH2, *1/*1, *1/*2, and *2/*2 (defective homozygote) were 45.8, 46.0, and 8.2%, respectively, for men. Drinking more than two drinks daily was associated with lower HDL levels in men with the defective genotypes compared with men with a normal genotype (55.6+/-0.9 vs. 51.2+/-0.9 mg/dl, mean+/-S.E., P<0.0001). Also, drinking more than 0.5 drinks daily was not associated with beneficial effects on HDL levels in women with defective ALDH2 genotypes. CONCLUSIONS: Alcohol intake did not have beneficial effects on HDL levels in the defective ALDH2 genotype and may not protect against CAD in subjects with defective ALDH2 genotypes. |
| Genetic variation in cholesterol absorption efficiency among inbred strains of mice Carter, C. P., P. N. Howles, et al. (1997), J Nutr 127(7): 1344-8. Abstract: The initial study utilized the outbred Black Swiss, the inbred 129/SvEv and their hybrid mice to test for possible genetic difference in cholesterol absorption efficiency. Female mice (10-12 wk old) were fed a lipid test meal containing 3Hcholesterol and beta-14Csitosterol by stomach tube. The amount of 3Hcholesterol excreted in the feces was determined as nonabsorbed cholesterol and was normalized based on the recovery of the nonabsorbable beta-14Csitosterol. The Black Swiss mice absorbed significantly less cholesterol than the 129/SvEv mice within a 24-h period. Cholesterol absorption efficiency of the hybrid mice varied widely and did not segregate with either parental group. Differences in cholesterol absorption efficiency were also observed among six different inbred strains of mice fed either a basal low fat diet or a high fat/high cholesterol diet for 3 wk. Cholesterol absorption efficiency did not differ among DBA/2, C57BL/6, C3H/He, BALB/c and AKR/J mice under basal dietary conditions. However, cholesterol absorption was significantly lower in the DBA/2 mice than in C57BL/6 and C3H/He mice after mice were fed a high fat/high cholesterol diet. Cholesterol absorption by the C57L/J mice did not differ from that of C57BL/6, C3H/He, BALB/c and AKR/J mice under basal diet conditions, but was significantly lower when mice were fed a high fat/high cholesterol diet. Cholesterol absorption efficiency differed between DBA/2 and C57L/J mice under both dietary conditions. These results suggest that cholesterol absorption is controlled by multiple genetic factors. |