| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| A dose-response relationship between sex hormone-induced change in hepatic triglyceride lipase and high-density lipoprotein cholesterol in postmenopausal women Colvin, P. L., Jr., B. J. Auerbach, et al. (1991), Metabolism 40(10): 1052-6. Abstract: In previous studies, we have demonstrated a temporal relationship between the postheparin hepatic triglyceride lipase (HTGL) response to sex steroids and the high-density lipoprotein (HDL) cholesterol response. To determine if this relationship is dose-dependent, we compared the effect of three graduated doses of orally administered estradiol and norgestrel in two groups of six postmenopausal women. With estradiol administration, postheparin HTGL activity decreased from 91 +/- 46 to 50 +/- 29 nmol/min/mL, baseline to high dose (P less than.05); HDL cholesterol increased from 54 +/- 6 to 64 +/- 10 mg/dL (P less than.05); HDL2 cholesterol increased from 16 +/- 4 to 23 +/- 7 mg/dL (P less than.05); and HDL3 cholesterol concentration did not change. With norgestrel administration, HTGL activity increased from 79 +/- 19 to 109 +/- 24 nmol/min/mL (P less than.05); HDL cholesterol decreased from 64 +/- 17 to 43 +/- 7 mg/dL (P less than.05); HDL2 cholesterol decreased from 21 +/- 17 to 6 +/- 5 mg/dL (P less than.05); and HDL3 cholesterol concentration decreased from 43 +/- 8 to 38 +/- 8 mg/dL (P less than.05). The HTGL activity response was inversely correlated with estrogen dose (rs = -.733, P =.0001) and directly correlated with progestin dose (rs =.895, P =.0001). The HDL cholesterol response was directly correlated with estrogen dose (HDL: rs =.741, P =.001; HDL2: rs =.586, P = 0.003) and inversely correlated with progestin dose (HDL: rs = -.933, P =.0001; HDL2: rs = -.866, P =.0001; HDL3: rs = -.576, P =.003).(ABSTRACT TRUNCATED AT 250 WORDS) |
| A dose-response study of the effects of dietary cholesterol on fasting and postprandial lipid and lipoprotein metabolism in healthy young men Ginsberg, H. N., W. Karmally, et al. (1994), Arterioscler Thromb 14(4): 576-86. Abstract: Despite many previous studies, controversy remains concerning the effects of dietary cholesterol on plasma cholesterol concentrations. In addition, the focus of previous studies has been fasting lipid and lipoprotein concentrations; there are no published studies with postprandial measurements. We studied the effects of four levels of dietary cholesterol intake on fasting lipid, lipoprotein, and apoprotein levels, as well as postprandial lipid levels, in a group of young, healthy men who were otherwise eating a low-fat, American Heart Association step 1 diet. Twenty young, healthy men completed a randomized, four-way crossover design study to test the effects of an American Heart Association step 1 diet containing 0, 1, 2, or 4 eggs per day. Dietary cholesterol ranged from 128 to 858 mg cholesterol per day. Each diet was eaten for 8 weeks, with a break between diets. Three fasting blood samples were obtained at the end of each diet period. In addition, blood samples were obtained just before and 2, 4, and 6 hours after ingestion of a standard lunch containing the various amounts of egg cholesterol. We also obtained blood 4 and 8 hours after the subjects ingested a standard, high-fat formula. Fasting plasma total cholesterol concentrations increased by 1.47 mg/dL (0.038 mmol/L) for every 100 mg dietary cholesterol added to the diet (P <.001). Low-density lipoprotein (LDL) cholesterol increased in parallel. Responsiveness varied but appeared to be normally distributed. Fasting plasma apoprotein B concentrations increased approximately 10% between the 0- and 4-egg diets and were correlated with changes in total and LDL cholesterol concentrations. Although there was a trend toward a greater response in men with an apoprotein E4 allele, this was not statistically significant. Fasting plasma cholesteryl ester transfer protein levels were higher only on the 4-egg diet, and changes in cholesteryl ester transfer protein levels between the 0- and 4-egg diets correlated with changes in total and LDL cholesterol. There were no differences in the postlunch or post-fat-formula responses of plasma lipids across the diets. Incubation of the 4-hour postlunch serum with J774 macrophages did not affect cell cholesteryl ester content at any level of dietary cholesterol. Cellular free cholesterol levels were slightly higher on each of the egg-containing diets versus the 0-egg diet. In summary, increases in dietary cholesterol resulted in linear increases in fasting total and LDL cholesterol in young, healthy men.(ABSTRACT TRUNCATED AT 400 WORDS) |
| A double mutant N543H+2393del9 allele in the LDL receptor gene in familial hypercholesterolemia: effect on plasma cholesterol levels and cardiovascular disease Castillo, S., G. Reyes, et al. (2002), Hum Mutat 20(6): 477. Abstract: Familial hypercholesterolemia is a genetic disorder caused by mutations in the LDL receptor gene. During a survey of mutations of LDL receptor gene in Spanish FH patients we found two mutations in the same allele: a missense N543H mutation in exon 11 and a 9bp inframe deletion (2393del9) located in exon 17. This double mutant allele was founded in 10 out of 458 unrelated patients: one homozygous FH N543H+2393del9 + N543H+2393del9, one compound heterozygote N543H+2393del9 + W-18X+E256K and 8 heterozygotes. Flow cytometric analysis showed a defective LDL binding (20% of normal value) and internalization (23%) in lymphocytes from the homozygous patient; furthermore, studies of mitogen-stimulated lymphocytes demonstrated that the ability of LDL to support cell proliferation was impaired. Unexpectedly, not all carriers of the double mutant allele develop hypercholesterolemia and, furthermore, cholesterol-lowering treatment of the homozygous patient resulted in a 58% LDL cholesterol reduction. In conclusion, the phenotypic expression in the homozygous and heterozygous patients presented here, as well as the LDL-receptor residual activity, allowed the classification of this mutation as mild extending the group of mild mutations found at homozygosity. |
| A double-blind placebo-controlled clinical trial compares the cholesterol-lowering effects of two different soy protein preparations in hypercholesterolemic subjects Hoie, L. H., E. C. Morgenstern, et al. (2005), Eur J Nutr 44(2): 65-71. Abstract: BACKGROUND: Soy protein is effective in lowering plasma cholesterol, LDL cholesterol and triglyceride concentrations. It has not been conclusively answered, whether and to what extent other soy constituents may also contribute to this effect. OBJECTIVE: To investigate the change in blood lipid levels after application of two soy-based supplements containing soy protein either without (SuproSoy) or with (Abacor) soy fiber and phospholipids in a randomized placebo-controlled triplearmed study. METHODS: 121 hypercholesterolemic adults (66 females, 55 males) were recruited and randomly assigned to one of three treatments. Over 8 weeks they received daily either 25 g soy protein (as a component of the supplements Abacor or SuproSoy) or 25 g milk protein (as a component of placebo). Serum lipids were measured at baseline and after 4, 6 and 8 weeks. RESULTS: After 8 weeks of supplementation total cholesterol levels were reduced by 8.0 +/- 9.6% (Abacor) and 3.4 +/- 8.3% (SuproSoy); LDL cholesterol levels by 9.7 +/- 11.7% (Abacor) and 5.4 +/- 11.6% (SuproSoy); and Apolipoprotein B levels by 6.9 +/- 14.6% (Abacor) and 4.0 +/- 12.4 % (SuproSoy). Serum levels of HDL cholesterol and triglycerides remained unchanged. CONCLUSIONS: A preparation combining isolated soy protein with soy fibers and phospholipids showed twice the lipid-lowering effect of a preparation containing isolated soy protein alone. Therefore, such soy-based supplements can be useful in reducing the cardiovascular risk. |
| A familial risk factor in cholesterol gallstone disease Durst, R. Y., R. Burvin, et al. (1996), J Clin Gastroenterol 23(4): 289-91. |
| A family focus program to lower blood cholesterol Key, J. O. and A. P. Rocchini (1991), J Am Diet Assoc 91(9): 1113-5. |
| A fiberoptic cholesterol biosensor with an oxygen optrode as the transducer Trettnak, W. and O. S. Wolfbeis (1990), Anal Biochem 184(1): 124-7. Abstract: A biosensor for the continuous optical determination of cholesterol is presented. Cholesterol oxidase is immobilized covalently on a nylon membrane and the consumption of oxygen is measured by following, via fiberoptic bundles, the changes in fluorescence of an oxygen-sensitive dye whose fluorescence is dynamically quenched by molecular oxygen. The dye is dissolved in a very thin silicone membrane placed beneath the enzyme layer. During interaction of the enzyme with cholesterol, oxygen is consumed, which is indicated by the fluorescent dye. At pH 7.25, the analytical range of the sensor is 0.2 to 3 mM and the time to reach a full steady state in a flowing solution ranges from 7 to 12 min. |
| A five-year follow-up study on blood pressure and serum cholesterol in junior high school children Omura, T., Y. Takizawa, et al. (1991), Nippon Koshu Eisei Zasshi 38(6): 417-24. Abstract: Blood pressure and serum cholesterol changes over a five-year period were studied in 299 junior high school children (127 males and 172 females) examined during 1980-1984 in Akita Prefecture, Japan. The six factors studied were height, weight, body mass index (by Minowa's method), systolic blood pressure, diastolic blood pressure and serum cholesterol. Mean values for systolic and diastolic blood pressure increased more than 10 mmHg during the five years in both sexes. Significant positive correlations between initial and follow-up blood pressure ('tracking') were observed. The correlation coefficients for systolic blood pressure in males and in females were 0.33 and 0.28 respectively, and those for diastolic blood pressure were 0.36 in males and 0.19 in females. While there were no significant differences in serum cholesterol levels between the two periods in either sex, the correlation coefficients, which were higher than those for blood pressure, were 0.55 in males and 0.45 in females. Among the six factors at each period, significant positive correlations were observed between height and systolic blood pressure at the initial period, and between obesity and systolic blood pressure at both periods in males and females. A significant positive relationship between obesity and serum cholesterol was seen at the follow-up period in both sexes. These data suggest that a moderate degree of 'tracking' occurs in blood pressure and serum cholesterol during childhood, and that obesity is an important factor related to blood pressure and serum cholesterol. |
| A fluorescence energy transfer study of lecithin-cholesterol vesicles in the presence of phospholipase C Wrenn, S. P., E. W. Kaler, et al. (1999), J Lipid Res 40(8): 1483-94. Abstract: We demonstrate Forster resonance energy transfer from dehydroergosterol to dansylated lecithin in lecithin-cholesterol vesicles and characterize the vesicles in the presence of the pro-nucleating enzyme, phospholipase C (PLC). Exposure to phospholipase C causes a temporary decrease in the dehydroergosterol to dansyl fluorescence ratio followed by an increase to and above the initial value. The temporary decrease in the fluorescence ratio results from an increase in the dansylated lecithin intensity that coincides with a dansyl blue shift. The extent of the blue shift correlates with the level of diacylglycerol generated in situ by PLC, suggesting an increased association between dansylated lecithin and cholesterol as membrane fluidity increases and membrane polarity decreases. The subsequent increase in the fluorescence ratio results from both an increase in the dehydroergsterol intensity and a concomitant decrease in the dansylated lecithin intensity of equal magnitude. This signifies a reduction in energy transfer from dehydroergosterol to dansylated lecithin and indicates an increased separation between the two fluorophores. The increase in the fluorescence ratio persists beyond the time scales for vesicle aggregation and fusion, as measured by turbidity, and precedes the onset of macroscopic cholesterol crystals observed with an optical microscope. Thus, the increased separation between dehydroergosterol and dansylated lecithin is consistent with a mechanism of cholesterol nucleation from the vesicles. Moreover, the onset and rate of increase in the fluorescence ratio correlate with the cholesterol:lecithin mole ratio of the vesicles. Fluorescence energy transfer from dehydroergosterol to dansylated lecithin therefore shows potential as a methodology for measuring cholesterol nucleation in model bile. |
| A fluorescent cholesterol analog traces cholesterol absorption in hamsters and is esterified in vivo and in vitro Sparrow, C. P., S. Patel, et al. (1999), J Lipid Res 40(10): 1747-57. Abstract: The fluorescent cholesterol analog 22-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3beta-ol (fluoresterol) was characterized as a tool for exploring the biochemistry and cell biology of intestinal cholesterol absorption. Hamsters absorbed fluoresterol in a concentration- and time-dependent manner, with an efficiency of about 15-30% that of cholesterol. Fluoresterol absorption was blocked by compounds known to inhibit cholesterol absorption, implying that fluoresterol interacts with those elements of the normal pathway for cholesterol absorption on which the inhibitors act. Confocal microscopy of small intestinal tissue demonstrated that fluoresterol was taken up by absorptive epithelial cells and packaged into lipoprotein particles, suggesting a normal route of intracellular trafficking. Uptake of fluoresterol was confirmed by biochemical analysis of intestinal tissue, and a comparison of (3)H cholesterol and fluoresterol content in the mucosa suggested that fluoresterol moved through the enterocytes more rapidly than did cholesterol. This interpretation was supported by measurements of fluoresterol esterification in the mucosa. Four hours after hamsters were given fluoresterol and (3)Hcholesterol orally, 44% of the fluoresterol in the intestinal mucosa was esterified, compared to 8% of the (3)Hcholesterol. Caco-2 cells took up 2- to 5-fold more (3)Hcholesterol than fluoresterol from bile acid micelles, and esterified 21-24% of the fluoresterol but only 1-4% of the (3)Hcholesterol. Thus fluoresterol apparently interacts with the proteins required for cholesterol uptake, trafficking, and processing in the small intestine. |
| A fluorometric assay for cholesterol reductase activity Yang, J. B. and D. C. Beitz (1992), Anal Biochem 206(2): 246-50. Abstract: A fluorometric method for the assay of cholesterol reductase activity from pea leaves (Pisum sativum) is presented. This method is based on the decrease in relative fluorescence occurring as a result of the oxidation of NADH when cholesterol is reduced catalytically to coprostanol by cholesterol reductase. The reaction mixture consisted of micellar cholesterol, NADH, and cytosol of pea leaves in a phosphate buffer. After incubation for 1 h, the reaction mixture were diluted with 2-(N-cyclohexylamino)ethanesulfonic acid buffer (50 mM, pH 10.0) to an appropriate concentration for NADH quantification. The relative fluorescence was measured at an excitation wavelength of 360 nm and at an emission wavelength of 460 nm. This fluorometric method is relatively rapid, simple, and inexpensive. The results obtained show close correlation (R = 0.997) with those obtained by the more time-consuming and expensive radiometric method for assay of cholesterol reductase activity. Results suggest that the fluorometric method is useful for the accurate determination of cholesterol reductase activity in biological specimens. |
| A fluorometric method of determining cholesterol esterase activity Pozdnev, V. F., K. S. Planutis, et al. (1991), Bioorg Khim 17(10): 1347-51. Abstract: A simple and highly specific method for estimating the cholesterol esterase activity is suggested. Cholesterol esterase (EC 3.1.1.13) is incubated with the emulsified substrate, cholesteryl-o-coumarate, at pH 6.6 to yield o-coumaric (trans-2-hydroxycinnamic) acid detected fluorimetrically (lambda exc 363 nm, lambda em 494 nm) at pH 10.4. The fluorescence associated with the unhydrolyzed substrate is negligible. Cholesteryl-o-coumarate is not hydrolyzed by pancreatic lipase, trypsin, or chymotrypsin under the above conditions. About 1 microgram of pancreatic cholesterol esterase can be determined upon 15 min incubation. The substrate was synthesized by condensation of o-acetoxy-trans-cinnamic acid with cholesterol using the di-tert-butyl pyrocarbonate--pyridine--4-dimethylaminopyridine system. |
| A food frequency questionnaire that rapidly and accurately assesses intake of fat, saturated fat, cholesterol, and energy Curtis, A. E., K. O. Musgrave, et al. (1992), J Am Diet Assoc 92(12): 1517-9. |
| A food-grade silicon dioxide is hypocholesterolemic in the diet of cholesterol-fed rats Peluso, M. R. and B. O. Schneeman (1994), J Nutr 124(6): 853-60. Abstract: Silicon dioxide, commonly referred to as silica, is present in plant cell walls and interstitial spaces, and is often found as a component of dietary fibers that have exhibited hypocholesterolemic activity in animals. The primary objective of this study was to determine the cholesterolemic effects of two different morphological forms of silicon in the diet of cholesterol-fed rats. Male Wistar rats were provided diets containing 1 g cholesterol/100 g diet, and 0.65 g Si/100 g diet as either a sodium salt (silicate group) or silicon dioxide, a synthetic silica polymer (silica group). Cellulose was used as a control (control group). The in vitro bile acid binding capacity of the SiO2 was also measured. After 44 d of diet administration, animals were deprived of food for 24 h and then killed. Plasma total, VLDL, and LDL cholesterol concentrations were 18%, 29%, and 26% lower, respectively, in the silica group than in the control group. However, liver cholesterol concentrations were not different among dietary treatments. During the initial 15 d of the study, average daily total fecal bile acids were 38% higher in the silica group than in the control group, but fecal bile acid outputs were not different for the remainder of the experiment. The silica polymer used in the feeding trial was found to adsorb 5 times more cholate than chenodeoxycholate, at pH 7.5 in vitro. In vivo, the potential for silica to enhance fecal cholic acid excretion, relative to chenodeoxycholic acid during the initial stage of the study, may have contributed to the hypocholesterolemic response to the silica diet.(ABSTRACT TRUNCATED AT 250 WORDS) |
| A fraction derived from brewer's yeast inhibits cholesterol synthesis by rat liver preparations in vitro Holdsworth, E. S., D. V. Kaufman, et al. (1991), Br J Nutr 65(2): 285-99. Abstract: Brewer's yeast was grown on a defined medium containing tracer 51Cr with or without added chromium. The two batches of yeast contained 10 microgram/g (high-Cr) or 80 ng/g (low-Cr). Extracts were prepared and fractionated. A third batch of yeast (third batch) was grown with added Cr, and fractionated. Rats were reared on either rat cubes (normal diet) or on a low-Cr diet (low-Cr), or on rat cubes with added cholestyramine (cholestyramine diet). Preparations of rat liver, both cell-free and intact hepatocytes, incorporated acetate-carbon into fatty acids and cholesterol. These processes were inhibited by a yeast fraction containing small, neutral, water-soluble compounds. The degree of inhibition was the same whether the liver came from normal rats or rats fed on the low-Cr diet. Similarly the inhibitory effect was found with identical amounts of extracts from low- or high-Cr yeasts. Therefore, Cr compounds do not appear to account for the inhibitory effects of brewer's yeast. Use of other substrates indicated that the site of inhibition of sterol synthesis was apparently between acetyl-CoA and mevalonate. One inhibitory substance was isolated from yeast and was found to be nicotinamide riboside. This may have been produced from NAD(P) during the preparation of yeast extracts, and it may be produced from dietary yeast supplements during digestion in vivo. Nicotinamide riboside may be partly responsible for the reported effects of yeast supplements on plasma lipids in humans. |
| A functional role for vimentin intermediate filaments in the metabolism of lipoprotein-derived cholesterol in human SW-13 cells Sarria, A. J., S. R. Panini, et al. (1992), J Biol Chem 267(27): 19455-63. Abstract: Numerous studies have indicated that cytoplasmic intermediate filaments (cIFs) can associate with cellular lipids. To determine if these interactions might have functional consequences, we have studied the lipid metabolism of human SW-13 adrenal tumor cell lines that either contain vimentin-type cIFs (vim+) or lack any detectable cIF network (vim-). Although there were no significant differences in phospholipid or glyceride synthesis, vim- cell lines had elevated levels of cholesterol synthesis and decreased cholesterol esterification, compared with vim+ cells. These differences in cholesterol synthesis and esterification were found to be due to an impaired ability of vim- cells to utilize low density lipoprotein (LDL)-derived cholesterol, although receptor-mediated endocytosis of LDL and the capacity of these cells to esterify endogenously produced cholesterol were not affected. Expression of a mouse vimentin cDNA in stably transfected cell lines, derived from vim- cells, restored the capacity of these cells to utilize LDL cholesterol. The uptake and metabolism of 3Hcholesterol linoleate-loaded LDL showed that the impaired ability of vim- cells to esterify LDL cholesterol was not associated with an accumulation of cellular free cholesterol but rather an increase in the appearance of 3Hcholesterol in the culture medium. These studies indicate that in SW-13 cells, the intracellular movement of LDL-derived cholesterol from the lysosome to the site of esterification is a vimentin-dependent process. |
| A genetic and correlation analysis of liver cholesterol concentration in rat recombinant inbred strains fed a high cholesterol diet Bottger, A., E. Lankhorst, et al. (1998), Biochem Biophys Res Commun 246(1): 272-5. Abstract: Liver cholesterol concentration in rats fed a high cholesterol diet, is under genetic control which is supported by significant differences observed among inbred strains. For instance, the Brown Norway (BN-Lx/Cub) rat developed a twofold higher liver cholesterol concentration than the spontaneously hypertensive rat (SHR/Ola). In the current study, we used 30 recombinant inbred (RI) strains, derived from BN-Lx and SHR progenitors, to locate quantitative trait loci (QTL) that are responsible for differences in liver cholesterol concentrations between the BN-Lx and SHR strains. The heritability of liver cholesterol was estimated to be 0.55 and a significant association was detected between concentration of liver cholesterol and the D10Cebrp1016s2 marker on chromosome 10 (lod score = 3.3); this putative QTL was responsible for nearly 64% of additive genetic variability and thus represents a major genetic determinant of liver cholesterol concentration. Liver cholesterol concentrations significantly correlated with intermediate density lipoprotein (IDL) cholesterol levels. |
| A genome search identifies major quantitative trait loci on human chromosomes 3 and 4 that influence cholesterol concentrations in small LDL particles Rainwater, D. L., L. Almasy, et al. (1999), Arterioscler Thromb Vasc Biol 19(3): 777-83. Abstract: Small, dense LDL particles are associated with increased risk of cardiovascular disease. To identify the genes that influence LDL size variation, we performed a genome-wide screen for cholesterol concentrations in 4 LDL size fractions. Samples from 470 members of randomly ascertained families were typed for 331 microsatellite markers spaced at approximately 15 cM intervals. Plasma LDLs were resolved by using nondenaturing gradient gel electrophoresis into 4 fraction sizes (LDL-1, 26.4 to 29.0 nm; LDL-2, 25.5 to 26.4 nm; LDL-3, 24.2 to 25.5 nm; and LDL-4, 21.0 to 24.2 nm) and cholesterol concentrations were estimated by staining with Sudan Black B. Linkage analyses used variance component methods that exploited all of the genotypic and phenotypic information in the large extended pedigrees. In multipoint linkage analyses with quantitative trait loci for the 4 fraction sizes, only LDL-3, a fraction containing small LDL particles, gave peak multipoint log10 odds in favor of linkage (LOD) scores that exceeded 3.0, a nominal criterion for evidence of significant linkage. The highest LOD scores for LDL-3 were found on chromosomes 3 (LOD=4.1), 4 (LOD=4.1), and 6 (LOD=2.9). In oligogenic analyses, the 2-locus LOD score (for chromosomes 3 and 4) increased significantly (P=0.0012) to 6.1, but including the third locus on chromosome 6 did not significantly improve the LOD score (P=0.064). Thus, we have localized 2 major quantitative trait loci that influence variation in cholesterol concentrations of small LDL particles. The 2 quantitative trait loci on chromosomes 3 and 4 are located in regions that contain the genes for apoD and the large subunit of the microsomal triglyceride transfer protein, respectively. |
| A genome-wide scan suggests a locus on chromosome 1q21-q23 contributes to normal variation in plasma cholesterol concentration Reed, D. R., E. Nanthakumar, et al. (2001), J Mol Med 79(5-6): 262-9. Abstract: To identify genes that influence plasma cholesterol, triglyceride, and high-density and low-density lipoproteins concentrations we conducted a genome-wide scan using 354 polymorphic markers spaced at 10-cM intervals in 75 obese but otherwise normal human families. The results of the genome scan using sibling pair analysis of quantitative phenotypes suggested that 1q21-q23 contains a locus that influences plasma cholesterol concentration. Chromosome 12 gave evidence of linkage to plasma triglyceride concentration (D12SPAH) and chromosomes 3, 6, 7, 10, 11, 17, and 20 yielded additional evidence of linkage for lipid phenotypes at lower levels of statistical significance. Allele sharing for markers near prominent candidate genes was either very weakly related or unrelated to sibling similarity for lipid concentrations. Together these results suggest that genes with important roles in regulating normal cholesterol and triglyceride concentrations do not coincide with the location of previously known candidate genes. |
| A genome-wide screen reveals evidence for a locus on chromosome 11 influencing variation in LDL cholesterol in the NHLBI Family Heart Study Coon, H., J. H. Eckfeldt, et al. (2002), Hum Genet 111(3): 263-9. Abstract: A genome scan was performed for low-density lipoprotein cholesterol concentration (LDL-C) in white subjects who were ascertained through the NHLBI Family Heart Study (FHS). The NIH Mammalian Genotyping Service (Marshfield, Wis.) genotyped 401 autosomal markers spaced at approximate 10-cM intervals. Additional FHS families were genotyped by the FHS Molecular Laboratory at the University of Utah for 243 markers; 645 subjects were typed in both laboratories so that a combined map of the 644 markers from the two screening sets (average distance of 5.46 cM) could be produced. Analyses were done on 2,799 genotyped subjects in 500 families where at least two genotyped persons in the family had measured LDL-C levels (average number of genotyped family members=5.95). The variance components method was used as implemented in GeneHunter (Kruglyak et al. 1996). Prior to analysis, each phenotype was adjusted, within sex, for age, age squared, body mass index, waist-hip ratio, alcohol, smoking, medication status for diabetes and hypertension, estrogen use, and field center location. Linkage analyses were performed, first excluding 305 subjects on lipid-lowering medications, then again including the data from these subjects. The highest peak was on chromosome 11 at 56.3-56.4 cM, with a maximum lod score of 3.72. Two genome scans of lipid traits in other populations have found peaks in this region. Other scores at or above 1.9 occurred on chromosomes 5 (lod=1.89 at 1.6 cM), 10 (lod=2.47 at 127.1 cM), 17 (lod=2.33 at 116.3 cM), and 21 (lod=2.74 at 45.2 cM). |