出版社：American Society for Biochemistry and Molecular Biology
摘要：We conducted a genome-wide scan using variance components linkageanalysis to localize quantitative-trait loci (QTLs) influencingtriglyceride (TG), high density lipoprotein-cholesterol (HDL-C),low density lipoprotein-cholesterol, and total cholesterol (TC)levels in 3,071 subjects from 459 families with atherogenicdyslipidemia. The most significant evidence for linkage to TGlevels was found in a subset of Turkish families at 11q22 [logarithmof the odds ratio (LOD) = 3.34] and at 17q12 (LOD = 3.44). Weperformed sequential oligogenic linkage analysis to examinewhether multiple QTLs jointly influence TG levels in the Turkishfamilies. These analyses revealed loci at 20q13 that showedstrong epistatic effects with 11q22 (conditional LOD = 3.15)and at 7q36 that showed strong epistatic effects with 17q12(conditional LOD = 3.21). We also found linkage on the 8p21region for TG in the entire group of families (LOD = 3.08).For HDL-C levels, evidence of linkage was identified on chromosome15 in the Turkish families (LOD = 3.05) and on chromosome 5in the entire group of families (LOD = 2.83). Linkage to QTLsfor TC was found at 8p23 in the entire group of families (LOD= 4.05) and at 5q13 in a subset of Turkish and Mediterraneanfamilies (LOD = 3.72).
These QTLs provide important clues for the further investigationof genes responsible for these complex lipid phenotypes. Thesedata also indicate that a large proportion of the variance ofTG levels in the Turkish population is explained by the interactionof multiple genetic loci.Abbreviations: cM, centimorgan; CVD, cardiovascular disease; FCHL, familial combined hyperlipidemia; GEMS, Genetic Epidemiology of Metabolic Syndrome; HDL-C, high density lipoprotein-cholesterol; LDL-C, low density lipoprotein-cholesterol; LOD, logarithm of the odds ratio; QTL, quantitative trait locus; TC, total cholesterol; TG, triglyceride
Supplementary key words cardiovascular disease • epistatic effects • genetic linkage analysis • metabolic syndrome • variance components analysis
