| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Smith-Lemli-Opitz syndrome; a special defect in cholesterol metabolism Aalfs, C. M., R. C. Hennekam, et al. (1996), Ned Tijdschr Geneeskd 140(28): 1463-6. Abstract: In a male neonate dysmaturity, microcephalia, a high nasal bridge, a long philtrum, broad dental ridges, schisis of the palatum molle, retrognathia, a small penis with a chorda, a small scrotum, bilateral inguinal hernia and bilateral syndactyly of the second and third toes were observed. The presence of the Smith-Lemli-Opitz (SLO) syndrome was suspected. By gas chromatography a severely decreased plasma cholesterol level (0.27 mmol/l) was found and an increased plasma 7-dehydrocholesterol level (0.24 mmol/l). The SLO syndrome is caused by a block in the cholesterol biosynthesis due to the autosomal recessive deficiency of 7-dehydrocholesterol reductase. The patient's condition improved with use of a cholesterol-enriched diet. |
| Smoking and atherosclerotic cardiovascular disease in men with low levels of serum cholesterol: the Korea Medical Insurance Corporation Study Jee, S. H., I. Suh, et al. (1999), Jama 282(22): 2149-55. Abstract: CONTEXT: Few studies have examined the interactive effects of smoking and serum cholesterol level on morbidity and mortality from cardiovascular dieseases. In East Asia, where the prevalence of smoking is among the highest in the world, morbidity and mortality from ischemic heart disease (IHD) is rapidly escalating. OBJECTIVES: To determine whether cigarette smoking is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in the Republic of Korea (South Korea), a population that has relatively low levels of serum cholesterol, and to determine whether serum cholesterol levels modify the risk relationship between smoking and ASCVD. DESIGN: Prospective cohort study with a follow-up period of 6 years (1993-1998). SETTING AND SUBJECTS: A total of 106745 Korean men aged 35 to 59 years who received health insurance from the Korea Medical Insurance Corporation and who had biennial medical evaluations in 1990 and 1992. MAIN OUTCOME MEASURES: Hospital admissions and deaths from IHD, cerebrovascular disease (CVD), and total ASCVD. RESULTS: At baseline, 61389 (58%) were current cigarette smokers and 64482 (60%) had a total cholesterol level of less than 5.17 mmol/L (200 mg/dL). Between 1993 and 1998, 1006 IHD events (176 per 100000 person-years), 1364 CVD events (238 per 100000 person-years), and 716 other ASCVD events (125 per 100000 person-years) occurred. In multivariate Cox proportional hazard models controlling for age, hypertension, hypercholesterolemia, and diabetes, current smoking increased the risk of IHD (risk ratio RR, 2.2; 95% confidence interval CI, 1.8-2.8), CVD (RR, 1.6; 95% CI, 1.4-1.8), and total ASCVD (RR, 1.6; 95% CI, 1.5-1.8). For each outcome, there were significant dose-response relationships with amount and duration of smoking. Throughout the range of serum cholesterol levels, current smoking significantly increased the risk of IHD and CVD. In the lowest quartile of serum cholesterol levels (<4.42 mmol/L 171 mg/dL), the RR from current smoking was 3.3 (95% CI, 1.7-6.2) for IHD and 1.6 (95% CI, 1.2-2.3) for CVD. There was no evidence of an interaction between smoking and serum cholesterol (P for interaction =.75.87, and.92 for IHD, CVD, and total ASCVD, respectively). CONCLUSIONS: This study demonstrates that in Korea smoking is a major independent risk factor for IHD, CVD, and ASCVD and that a low cholesterol level confers no protective benefit against smoking-related ASCVD. |
| Smoking and plasma lipoproteins in man: effects on low density lipoprotein cholesterol levels and high density lipoprotein subfraction distribution Freeman, D. J., B. A. Griffin, et al. (1993), Eur J Clin Invest 23(10): 630-40. Abstract: In a survey of a healthy population (n = 197), LDL cholesterol, plasma triglycerides and VLDL triglycerides were found to be substantially increased and plasma HDL cholesterol decreased in smokers. The lipid-associated atherogenic risk in smokers as assessed by the LDL/HDL ratio was significantly higher 2.89 (SD 1.18, n = 63) than in non-smokers 2.38 (SD 0.98, n = 86) P < 0.01. The lower HDL level found in smokers was explained by a lower HDL-2 subfraction as determined by analytical ultracentrifugation. HDL 2b, 2a and 3a, measured by gradient gel electrophoresis, were all lower in the smokers but this was only significant for HDL 2a. Smoking had no effect on Lp(a) levels. HDL cholesterol and HDL-2 were strongly negatively correlated whereas LDL cholesterol and LDL/HDL ratio were strongly positively correlated with the plasma triglyceride concentration. There was a small but significant reduction in plasma CETP activity non-smokers 49% t/microliter (SD 17, n = 90), smokers 43% t/microliter (SD 17, n = 66) P < 0.05 but CETP activity was not correlated with any measure of HDL in this population. Smoking was found to be an important independent contributor to the variation in plasma triglyceride, HDL, HDL-2 and LDL/HDL ratio. After correcting for sex, age, BMI, alcohol consumption, oral contraceptive use and plasma triglycerides smoking was still found to be significantly associated with HDL and the LDL/HDL ratio. Upon adjustment for covariant factors the mean differences between smokers and non-smokers for HDL cholesterol, HDL-2 and LDL/HDL were 0.15 mM, 16 mg dl-1 and 0.39 respectively. There appeared to be important sex differences in the influence of smoking on plasma lipoproteins. In women the main impact of smoking was on triglyceride levels and they in turn affected LDL and HDL. In contrast, in men, smoking had little impact on triglycerides and affected HDL more directly. We conclude that smoking cigarettes has an important effect on plasma lipoprotein metabolism through multiple mechanisms. |
| Smoking as cardiovascular risk factor in low cholesterol population: the Hisayama Study Fujishima, M., Y. Kiyohara, et al. (1992), Clin Exp Hypertens A 14(1-2): 99-108. Abstract: Cigarette smoking as a risk factor for cerebro- and cardiovascular diseases was studied in a long-term prospective population survey which has been carried out in a Japanese rural community, Hisayama. In this population, the incidence of thrombotic brain infarction (TBI) was much higher than that of coronary heart disease (CHD) over a 26-year follow-up period. Cigarette smoking was strongly related to the occurrence of CHD but not to TBI. Comparing the incidence of CHD and TBI between first or early cohort (1961-74) and second or recent cohort (1974-87) during the 13-year follow-up, the incidence remained unchanged for CHD, while it significantly decreased for TBI in recent population. The prevalence of cigarette smoking as well as hypertension decreased in recent years, while hypercholesterolemia, obesity, and glucose intolerance increased. Smoking is a major contributor to CHD for men in both cohorts, but it is not any more for women in the recent cohort. |
| Smoking prevents the intravascular remodeling of high-density lipoprotein particles: implications for reverse cholesterol transport Zaratin, A. C., E. C. Quintao, et al. (2004), Metabolism 53(7): 858-62. Abstract: Smoking is a leading cause of atherosclerosis acting trough a wide spectrum of mechanisms, notably the increase of the proatherogenic effect of dyslipidemia. However, a severe atherosclerotic disease is frequently observed in smokers who do not present an overt dyslipidemia. In the present study, we sought to determine if abnormalities in lipid metabolism occur in normolipidemic smokers, focusing especially on the components of intravascular remodeling of high-density lipoprotein (HDL) For this purpose, we measured lipid transfer proteins and enzymes involved in the reverse cholesterol transport (RCT) system in 29 adults: 15 smokers and 14 controls. The blood samples were drawn in the fasting state, immediately after the smokers smoked 1 cigarette. The composition of HDL particles was analyzed after isolation of HDL fractions by microultracentrifugation. We observed that normolipidemic smokers present higher total plasma and HDL phospholipids (PL) (P <.05), 30% lower postheparin hepatic lipase (HL) activity (P <.01), and 40% lower phospholipid transfer protein (PLTP) activity (P <.01), as compared with nonsmokers. The plasma cholesteryl ester transfer protein (CETP) mass was 17% higher in smokers as compared with controls (P <.05), but the endogenous CETP activity corrected for plasma triglycerides (TG) was in fact 57% lower in smokers than in controls (P <.01). Lipid transfer inhibitor protein activity was also similar in both groups. In conclusion, the habit of smoking induces a severe impairment of many steps of the RCT system even in the absence of overt dyslipidemia. Such an adverse effect might favor the atherogenicity of smoking. |
| Smoking, blood pressure and serum cholesterol-effects on 20-year mortality Houterman, S., W. M. Verschuren, et al. (2003), Epidemiology 14(1): 24-9. Abstract: BACKGROUND: To study the impact of smoking and blood pressure conditional on serum total cholesterol levels, we investigated the 20-year mortality risk associated with high systolic blood pressure (> or =140 mmHg) and smoking, at low (<5.2 mmol/Liter), medium (5.2-6.49mmol/Liter), and high (> or =6.5 mmol/Liter) serum total cholesterol levels. METHODS: The study population comprised a cohort of 50,000 men and women age 30-54 years, examined between 1974 and 1980, in five Dutch towns. The duration of follow-up averaged 20 years. Age-adjusted relative risks (RRs) for mortality from coronary heart disease (CHD), cardiovascular diseases (CVD) and all causes were estimated, for six risk profiles (based on levels of total cholesterol, systolic blood pressure and smoking), using Cox proportional hazards analysis. RESULTS: Given a low cholesterol level, smoking had a larger impact than elevated blood pressure on CHD, CVD and all-cause mortality. The combination of elevated blood pressure and smoking among persons with low cholesterol was associated with RRs of 3.0 for CHD, 6.0 for CVD and 4.1 for all-cause mortality in men, and 2.3, 3.6 and 2.6, respectively, in women. Among persons with high cholesterol, the combination of high blood pressure and smoking was associated with RRs of 9.7 for CHD, 13.9 for CVD and 5.7 for all-cause mortality in men, and 15.9, 9.3 and 4.3, respectively, in women. For each risk profile, the absolute number of CHD, CVD and total deaths was larger in men than in women. CONCLUSIONS: The results demonstrate the potential power of a multifactorial approach to risk factor reduction in the prevention of cardiovascular diseases and all-cause mortality. |
| Smoking, low density lipoprotein cholesterol, fibrinogen and myocardial infarction before 41 years of age: a Danish case-control study von Eyben, F. E., E. Mouritsen, et al. (2002), J Cardiovasc Risk 9(3): 171-8. Abstract: BACKGROUND: Of major coronary risk factors, smoking and total cholesterol were significant in a previous Danish case-control study of myocardial infarction at a young age. OBJECTIVE: To determine whether smoking was an important coronary risk factor in the context of new and major anthropometric and biochemical risk factors for myocardial infarction in individuals less than 41 years of age. METHODS: A prevalence hospital-based matched case-control study of young individuals. We selected 22 Caucasian cases and 24 Caucasian controls without coronary heart disease matching for age and gender and studied a series of major coronary risk factors and newer anthropometric and biochemical variables. RESULTS: In conditional univariate logistic regression analyses, the following factors were significantly associated with the coronary risk: family history, social class, smoking, intraabdominal adipose tissue area as percentage of total abdominal adipose tissue area on a CT scan, glycosylated haemoglobin level, systolic blood pressure, total cholesterol, low density lipoprotein (LDL) cholesterol, homocysteine, and fibrinogen levels (P < 0.05). However, in multiple conditional logistic regression analyses, only smoking, LDL cholesterol, and fibrinogen levels remained significant. Ten cases (46%) and none of the 24 controls were smokers with a LDL cholesterol level 4.5 mmol/l and a fibrinogen level 3.7 g/l (P = 0.0003, Fisher's exact test). CONCLUSION: Out of a series of major and newer coronary risk factors in young Western Caucasians, smoking, and levels of LDL cholesterol, and fibrinogen were independent significant coronary risk factors. The findings need to be validated in prospective studies. |
| SNAREs are concentrated in cholesterol-dependent clusters that define docking and fusion sites for exocytosis Lang, T., D. Bruns, et al. (2001), Embo J 20(9): 2202-13. Abstract: During exocytosis, SNARE proteins of secretory vesicles interact with the corresponding SNARE proteins in the plasmalemma to initiate the fusion reaction. However, it is unknown whether SNAREs are uniformly distributed in the membrane or whether specialized fusion sites exist. Here we report that in the plasmalemma, syntaxins are concentrated in 200 nm large, cholesterol-dependent clusters at which secretory vesicles preferentially dock and fuse. The syntaxin clusters are distinct from cholesterol-dependent membrane rafts since they are Triton X-100-soluble and do not co-patch with raft markers. Synaptosomal-associated protein (SNAP)-25 is also clustered in spots, which partially overlap with syntaxin. Cholesterol depletion causes dispersion of these clusters, which is associated with a strong reduction in the rate of secretion, whereas the characteristics of individual exocytic events are unchanged. This suggests that high local concentrations of SNAREs are required for efficient fusion. |
| So, Doc. what's my cholesterol? Frustrations of discussing the physical exam Brown, S. J. (1998), Postgrad Med 104(4): 23-4. |
| Social worlds, actor-networks and controversy: the case of cholesterol, dietary fat and heart disease Garrety, K. (1997), Soc Stud Sci 27(5): 727-73. Abstract: Knowledge which links dietary fat and cholesterol to coronary heart disease (CHD) has been controversial for more than forty years. While policies advocating fat and cholesterol restriction are now deeply ingrained in affluent western societies, the scientific 'facts' on which they are supposedly based are highly contested. Applying concepts from actor-network theory and the symbolic interactionist social worlds approach, I argue that knowledge and dietary recommendations relating to cholesterol, fat and CHD are the outcome of complex social negotiations which can only be understood in their cultural, commercial and political contexts. Policies were framed in the 1960s before 'proof' of their efficacy was available. Since then, ambiguous experimental results have been shaped to support the policies. I argue that, despite its many attractive features, actor-network theory cannot adequately deal with protracted controversies. Social worlds theory provides a much more useful framework for investigating long debates in which the 'facts' remain elusive. |
| Sodium azide lowers cholesterol readings on the "Reflotron," Poon, R. and I. Hinberg (1990), Clin Chem 36(6): 1252-3. |
| Solid-state 2H NMR studies of the effects of cholesterol on the acyl chain dynamics of magnetically aligned phospholipid bilayers Tiburu, E. K., P. C. Dave, et al. (2004), Magn Reson Chem 42(2): 132-8. Abstract: We report the utilization of magnetically aligned phospholipid bilayers (bicelles) to study the effects of cholesterol in phospholipid bilayers for both chain perdeuterated DMPC and partially deuterated alpha-2,2,3,4,4,6-d(6)-cholesterol using (2)H solid-state NMR spectroscopy. The quadrupolar splittings at 40 degrees C were 25.5 and 37.7 kHz, respectively, for the 2,4-(2)H(eq) and 2,4-(2)H(ax) deuterons when the bilayer normal of the discs was aligned perpendicular to the static magnetic field. The quadrupolar splittings were doubled when Yb(3+) ions were added to flip the bicelles 90 degrees such that the bilayer normal was colinear with the magnetic field. The results suggest that cholesterol is incorporated into the bicelle discs. For chain perdeuterated DMPC-d(54), incorporated into DMPC-DHPC bicelle discs, the individual quadrupolar splittings of the methylene and methyl groups doubled on going from the perpendicular to the parallel alignment. Also, the presence of cholesterol increased the overall ordering of the acyl chains of the phospholipids. S(CD) (i) calculations were extracted directly from the (2)H quadrupolar splittings of the chain perdeuterated DMPC. The order parameter, S(CD) (i), calculations clearly indicated an overall degree of ordering of the acyl chains in the presence of cholesterol. We also noted a disordering effect at higher temperatures. This study demonstrates the ease with which (2)H order parameters can be calculated utilizing magnetically aligned phospholipid bilayers when compared with randomly dispersed membrane samples. |
| Solitary versus multiple cholesterol gallbladder stones. Mechanisms of formation and growth Wolpers, C. and A. F. Hofmann (1993), Clin Investig 71(6): 423-34. Abstract: The development and growth pattern of solitary and multiple cholesterol gallbladder stones was defined using cholecystography in a prospective study of 48 patients whose initial cholecystograms indicated a stone-free gallbladder and who developed gallstones within the subsequent 5 years. Radiological observations performed over 365 patient-years were complemented by macroscopic examination, radiograms, scanning electron microscopy, and chemical analysis of gallstones from these and other patients obtained at cholecystectomy. Solitary gallstones were found to develop after a precursor phase of over 2 years during which free-floating crystal laminae of cholesterol formed. These laminae subsequently aggregated loosely and underwent external compaction and internal remodeling by movement of cholesterol molecules to form compact spheroids. A single lamina was observed to function as a nucleus for the development of a solitary stone shaped as an ellipsoid. About 10% of solitary stones were found to have a solitary pigment stone in their center. In contrast, multiple cholesterol gallstones formed without a precursor phase. Innumerable, very thin cholesterol crystals appeared which very abruptly aggregated to form spheres of up to 1 mm in diameter. Within 3 months a second aggregation took place in which these spheres colaesced to form mulberry stones. Mulberry stones in turn were transformed either to faceted stones (if many were present in the gallbladder) or to barrel stones (if few were present) over a period of 3 years. It is proposed that temporary occlusion of the cystic duct leads to supersaturation of bile with calcium bilirubinate and/or calcium carbonate which in turn promotes deposition of either or both of these calcium salts on the surface of single or multiple gallstones. For multiple gallstones, this process or the deposition of additional cholesterol crystals seals the gallstone surface and is followed by metamorphosis of the stone center. |
| Solubility of cholesterol in the crystal-free gallbladder bile of gallstone patients Jungst, D., E. Gussmann, et al. (2004), J Lab Clin Med 144(3): 134-40. Abstract: Supersaturation of bile with cholesterol is generally considered the driving force of cholesterol precipitation. However, in most investigations the amount of cholesterol crystals is included in the calculation of the cholesterol saturation index (CSI). We therefore studied the solubility of cholesterol in crystal-free gallbladder bile from gallstone patients. Our results demonstrate significantly (P <.05) higher CSIs (1.4 +/- 0.5 and 1.4 +/- 0.4 vs 1.1 +/- 0.4, mean +/- SD) in crystal-free gallbladder bile from 66 patients with cholesterol stones and 21 patients with mixed stones compared with those in 30 patients with pigment stones and a significant difference (P <.001) in the amount of cholesterol in vesicles (19.2% +/- 13.7% and 14.3% +/- 11.6 % vs 4.2% +/- 5.9%) and of the crystal-observation time (COT; 1-21 days, median 2 days and 1-21 days, median 3 days, vs 3-21 days, median 21 days). We detected a positive correlation (r =.24, P <.01) between the percentage of cholesterol in vesicles and the CSI and a negative correlation between COT and CSI (r = -.23, P <.02) and COT and the percentage of cholesterol in vesicles (r = -.52, P <.001). However, in 14 of 30 gallbladder-bile specimens from patients with pigment stones but in just 5 of 21 specimens from patients with mixed stones patients and 12 of 66 specimens from patients with cholesterol stones, the distribution of cholesterol in different phases (mixed micelles, vesicles, and crystals) was within the limits of solubility determined in previous studies of model bile. Therefore, in addition to the relative composition of biliary lipids, nonlipid components exert considerable influence on the solubility of cholesterol in the gallbladder bile of gallstone patients. |
| Solubilization of cholesterol and polycyclic aromatic compounds into sodium bile salt micelles (part 2) Matsuoka, K., Y. Kuranaga, et al. (2002), Biochim Biophys Acta 1580(2-3): 200-14. Abstract: The aqueous solubility of cholesterol was determined over the temperature range from 288.2 to 318.2 K with intervals of 5 K by the enzymatic method. The solubility was (3.7+/-0.3)x10(-8) mol dm(-3) (average +/- S.D.) at 308.2 K. The maximum additive concentrations of cholesterol into the aqueous micellar solutions of sodium deoxycholate (NaDC), sodium ursodeoxycholate (NaUDC), and sodium cholate (NaC) were spectrophotometrically determined at different temperatures. The cholesterol solubility increased in the order of NaUDC |
| Solubilization of multilamellar liposomes of egg yolk lecithin by the bile salt sodiumtaurodeoxycholate and the effect of cholesterol--a rapid-ultrafiltration study Muller, K. and A. Schuster (1990), Chem Phys Lipids 52(2): 111-27. Abstract: The solubilization of multilamellar egg yolk lecithin liposomes by sodiumtaurodeoxycholate in aqueous phase was studied by ultrafiltration as a function of time, bile salt and cholesterol concentration. The corresponding equilibrium states were analysed. Complete solubilization was achieved at total bile salt/lecithin molar mixing ratios of approximately 5. The minimum ratio to start solubilization was 0.1, corresponding to a free bile salt concentration of only 5% of the critical micelle concentration (CMC). Mean equilibrium constants for the partition of bile salts between non-filterable aggregates and filterable mixed micelles and also the free bile salt concentration were determined. Sodiumtaurodeoxycholate had a higher affinity for small mixed micelles than for lamellar mixed aggregates especially in the presence of cholesterol, which reduces the degree and rate of the solubilization process. A non-homogeneous distribution of bile salts in the lipid phase was detected at low bile salt concentrations. |
| Solubilization of phytosterols in diacylglycerol versus triacylglycerol improves the serum cholesterol-lowering effect Meguro, S., K. Higashi, et al. (2001), Eur J Clin Nutr 55(7): 513-7. Abstract: OBJECTIVE: This study was performed to investigate the difference in the serum-cholesterol- and triglyceride-lowering activities between phytosterols dissolved in diacylglycerol (PS/DG) and dispersed in triacylglycerol (PS/TG). The effects of the solvent on the concentrations of serum beta-sitosterol and campesterol were examined. DESIGN: The study had a randomised crossover design. SUBJECTS: Twelve healthy normocholesterolemic or moderately hypercholesterolemic men aged 29-50 y participated in this study. INTERVENTIONS: For 2 weeks before the test period (designated as the control period), all subjects consumed control mayonnaise (PS free) daily with supper and were randomly assigned to two groups for the 2 week test period; one group was given mayonnaise containing PS (500 mg/day) dissolved in DG (10 g/day), and the other mayonnaise containing PS (500 mg/day) dispersed in TG (10 g/day). After a wash out period consuming control PS-free mayonnaise for 4 weeks, the groups were reversed for 2 weeks. RESULTS: PS/TG feeding had no effect on the serum cholesterol level. In contrast, PS/DG feeding significantly reduced the total and LDL cholesterol levels from the initial value of 5.57 to 5.31 mmol/l (4.7%; P<0.05) and from 3.69 to 3.39 mmol/l (7.6%; P<0.05), respectively. Moreover, the degree of total cholesterol reduction induced by PS/DG feeding in the test period was significantly greater than that induced by PS/TG feeding (P<0.05). In addition, the serum beta-sitosterol and campesterol concentrations did not change during the PS/TG or PS/DG feeding periods. CONCLUSIONS: Dissolution of PS in DG had a better serum cholesterol lowering effect than dissolution in TG. SPONSORSHIP: Kao Corporation. |
| Soluble dietary fiber and cholesterol influence in vivo hepatic and intestinal cholesterol biosynthesis in rats Arjmandi, B. H., J. Craig, et al. (1992), J Nutr 122(7): 1559-65. Abstract: Ninety-six male Sprague-Dawley rats were randomly assigned to eight dietary treatments. Rats were fed, with ad libitum access, diets containing 10% dietary fiber as cellulose (control), pectin, psyllium or oat bran with or without 0.3% added cholesterol for 3 wk. Among cholesterol-fed rats, liver total cholesterol was significantly lower in rats fed diets supplemented with either pectin or psyllium compared with those fed cellulose. In contrast, rats fed oat bran with cholesterol had significantly higher liver cholesterol concentrations compared with cellulose-fed animals. Liver total lipid concentrations were significantly lower in groups fed pectin and psyllium with or without dietary cholesterol compared with cellulose-fed controls. Pectin feeding with or without dietary cholesterol significantly lowered plasma total cholesterol compared with cellulose feeding. Oat bran had no effect on plasma total cholesterol compared with control diets. Hepatic sterol synthesis was significantly greater for animals fed soluble dietary fibers compared with those fed cellulose, but the effect on intestinal sterol synthesis was less pronounced. |
| Soluble dietary fiber protects against cholesterol gallstone formation Schwesinger, W. H., W. E. Kurtin, et al. (1999), Am J Surg 177(4): 307-10. Abstract: BACKGROUND: Epidemiological studies have suggested that soluble dietary fibers are hypocholesterolemic and may inhibit cholelithiasis. METHODS: Thirty prairie dogs were placed on a cholesterol-supplemented lithogenic diet. Ten animals received 5% psyllium (PSY) and 10 animals received 5% cellulose. After 6 weeks all gallbladders were inspected for stones; blood and bile were collected for analysis. RESULTS: Cholesterol stones were present in 8 of 10 of the control animals, in 6 of 10 of the cellulose group, and 3 of 10 of the PSY animals (P <0.05). Concentrations of cholesterol and chenodeoxycholic acid (CDCA) were significantly lower in the PSY group compared with controls (0.49 versus 0.88 mM and 4.2 versus 9.2 mM, respectively) leading to a significant reduction in the cholesterol saturation index (0.62 versus 1.2). CONCLUSIONS: A dietary soluble fiber (PSY) inhibits cholesterol stone formation by reducing the biliary cholesterol saturation index. This protective effect is associated with a selective decrease in biliary cholesterol and CDCA. |
| Soluble epoxide hydrolase variant (Glu287Arg) modifies plasma total cholesterol and triglyceride phenotype in familial hypercholesterolemia: intrafamilial association study in an eight-generation hyperlipidemic kindred Sato, K., M. Emi, et al. (2004), J Hum Genet 49(1): 29-34. Abstract: Plasma lipid and lipoprotein in general reflect the complex influences of multiple genetic loci, for instance, even familial hypercholesterolemia (FH), a representative example of monogenic hyperlipidemia, often presents with phenotypic heterogeneity. In the course of investigating familial coronary artery disease in Utah, we studied 160 members of an eight-generation extended family of FH in which 69 members were affected with type IIa hyperlipoproteinemia (HLPIIa; high plasma cholesterol) and ten with type IIb hyperlipoproteinemia (HLPIIb; high plasma cholesterol as well as plasma triglyceride). Soluble epoxide hydrolase (EPHX2, sEH) plays a role in disposition of epoxides in plasma lipoprotein particles. Intrafamilial correlation analysis of the modifier effect of Glu287Arg substitution in the EPHX2 gene was carried out among 79 LDLR mutation carriers and 81 noncarriers. In the carriers, plasma cholesterol levels were elevated among carriers of the 287Arg allele (mean +/- SD=358 +/- 72 mg/dl) in comparison with 287Glu homozygotes (mean +/- SD=302 +/- 72 mg/dl) (p=0.0087). Similarly, in the LDLR mutation carriers, the plasma triglyceride levels were elevated among carriers of the 287Arg allele (mean +/- SD=260 +/- 100 mg/dl) in comparison with 287Glu homozygotes (mean +/- SD=169 +/- 83 mg/dl) (p=0.020). No such gene-interactive effect was observed among noncarriers of the LDLR mutation. Half of the patients who presented with HLPIIb had inherited a defective LDLR allele as well as an EPHX2-287Arg allele, whereas the majority who presented with HLPIIa had a defective LDLR allele but not an EPHX2-287Arg allele. These results indicate a significant modification of the phenotype of FH with defective LDLR allele by EPHX2-287Arg variation in our studied kindred. |