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Journal of Lipid Research


Reference:

Yi Yu, Diego F. Wyszynski, Dawn M. Waterworth, Steven D. Wilton, Philip J. Barter, Y. Antero Kesäniemi, Robert W. Mahley, Ruth McPherson, Gérard Waeber, Thomas P. Bersot, Qianli Ma*, Sanjay S. Sharma, Douglas S. Montgomery, Lefkos T. Middleton, Scott S. Sundseth, Vincent Mooser, Scott M. Grundy and Lindsay A. Farrer, J Lipid Res. 2005 Oct;46(10):2202-13. Epub 2005 Aug 1.

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Abstract:

We conducted a genome-wide scan using variance components linkage analysis to localize quantitative-trait loci (QTLs) influencing triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol, and total cholesterol (TC) levels in 3,071 subjects from 459 families with atherogenic dyslipidemia. The most significant evidence for linkage to TG levels was found in a subset of Turkish families at 11q22 [logarithm of the odds ratio (LOD) = 3.34] and at 17q12 (LOD = 3.44). We performed sequential oligogenic linkage analysis to examine whether multiple QTLs jointly influence TG levels in the Turkish families. These analyses revealed loci at 20q13 that showed strong 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 8p21 region for TG in the entire group of families (LOD = 3.08). For HDL-C levels, evidence of linkage was identified on chromosome 15 in the Turkish families (LOD = 3.05) and on chromosome 5 in the entire group of families (LOD = 2.83). Linkage to QTLs for TC was found at 8p23 in the entire group of families (LOD = 4.05) and at 5q13 in a subset of Turkish and Mediterranean families (LOD = 3.72).

These QTLs provide important clues for the further investigation of genes responsible for these complex lipid phenotypes. These data also indicate that a large proportion of the variance of TG levels in the Turkish population is explained by the interaction of 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.

The American Journal of Cardiology


Reference:

Wyszynski DF, Waterworth DM, Barter PJ, Cohen J, Kesaniemi YA, Mahley RW, McPherson R, Waeber G, Bersot TP, Sharma SS, Nolan V, Middleton LT, Sundseth SS, Farrer LA, Mooser V, Grundy SM. Relation between atherogenic dyslipidemia and the Adult Treatment Program-III definition of metabolic syndrome (Genetic Epidemiology of Metabolic Syndrome Project). Am J Cardiol. 2005 Jan 15; 95(2):194-8.

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Abstract:

Genetic Epidemiology of Metabolic Syndrome is a multinational, family-based study to explore the genetic basis of the metabolic syndrome. Atherogenic dyslipidemia (defined as low plasma high-density lipoprotein cholesterol with elevated triglycerides (<25th and >75th percentile for age, gender, and country, respectively) identified affected subjects for the metabolic syndrome. This report examines the frequency at which atherogenic dyslipidemia predicts the metabolic syndrome of the National Cholesterol Education Program Adult Treatment Panel III (ATP-III). One thousand four hundred thirty-six (854 men/582 women) affected patients by our criteria were compared with 1,672 (737 men/935 women) unaffected persons. Affected patients had more hypertension, obesity, and hyperglycemia, and they met a higher number of ATP-III criteria (3.2 ± 1.1 SD vs 1.3 ± 1.1 SD, p <0.001). Overall, 76% of affected persons also qualified for the ATP-III definition (Cohen's k 0.61, 95% confidence interval 0.59 to 0.64), similar to a separate group of 464 sporadic, unrelated cases (75%). Concordance increased from 41% to 82% and 88% for ages =35, 36 to 55, and =55 years, respectively. Affected status was also independently associated with waist circumference (p <0.001) and fasting glucose (p <0.001) but not systolic blood pressure (p = 0.43). Thus, the lipid-based criteria used to define affection status in this study substantially parallels the ATP-III definition of metabolic syndrome in subjects aged >35 years. In subjects aged <35 years, atherogenic dyslipidemia frequently occurs in the absence of other metabolic syndrome risk factors.