Genome-wide linkage scan for factors of metabolic syndrome in a Chinese population

Abstract

BackgroundShared genetic factors may contribute to the phenotypic clustering of different components of the metabolic syndrome (MES). This study aims to identify genetic loci that contribute to individual or multiple factors related to MES.ResultsWe studied 478 normoglycemic subjects ascertained through 163 families participating in the Hong Kong Family Diabetes Study. Factor analysis on 15 MES-related traits yielded 6 factors including adiposity factor (body mass index, waist and hip circumferences), insulin factor (fasting insulin and insulin AUC during OGTT), glucose factor (fasting glucose and glucose AUC during OGTT), TC-LDLC factor (total cholesterol and LDL-cholesterol), blood pressure factor (systolic and diastolic blood pressure) and TG-HDLC factor (triglycerides and HDL-cholesterol). Genome-wide linkage analyses were performed on these factors using variance component approach. Suggestive evidence for linkage (LOD = 1.24 - 2.46) were observed for adiposity factor (chromosome 1 at 187 cM, chromosome 9 at 34 cM and chromosome 17 at 10 cM), insulin factor (chromosome 2 at 128 cM, chromosome 5 at 21 cM and chromosome 12 at 7 cM), glucose factor (chromosome 7 at 155 cM), TC-LDLC factor (chromosome 7 at 151 cM and chromosome 13 at 15 cM) and TG-HDLC factor (chromosome 7 at 155 cM).ConclusionsIn summary, our findings suggest the presence of susceptibility loci that influence either single (chromosomes 1, 2, 5, 9, 12, 13 and 17) or multiple factors (chromosome 7) for MES in Hong Kong Chinese without diabetes.

A prevalent caveolin-1 gene variant is associated with the metabolic syndrome in Caucasians and Hispanics

“…The association between the CAV1 variant and dyslipidemia is supported by genome-wide studies showing association of CAV1 gene proximal regions to low HDL and high triglycerides in two ethnically different cohorts [26, 35, 36]. Additionally, CAV1 KO mice display alterations in lipid composition (triglycerides, LDL and HDL), lending further support to a role for CAV1 in the complex regulation of lipoprotein metabolism and cholesterol efflux [8].…”

“…To date, information concerning the CAV1 gene and MetS is scarce, and is mainly based on animal studies [10, 25]. Of note, a particular region in chromosome 7 close to the CAV1 gene has been linked to both glucose and lipid factors but not increased adiposity in Asians, being the most associated region to both metabolic traits [26]. Also, linkage analysis showed that a region close to 7q.31 where CAV1 is located was related to metabolic syndrome [27].…”

Association of Genetic Variants in the Adiponectin Gene with Metabolic Syndrome: A Case-Control Study and a Systematic Meta-Analysis in the Chinese Population

“…Genome-wide linkage studies in multiple populations found evidence for linkage of MetS on chromosome 1, 2, 3q37, 7q, 16 [17]–[21]. Principal component factor analysis was also used to define quantitative phenotypes to identify the underlying genetic basis of MetS [22]–[30]. Although a number of quantitative trait loci (QTLs) were successfully identified, no specific gene or mutation has been found as a result of these linkage studies.…”

Fast, exact linkage analysis for categorical traits on arbitrary pedigree designs

“…Ventricular arrhythmia in German Shepherds is a complex phenotype which is likely to be influenced by many loci of small effects, so our power to detect any given locus is likely to be low, particularly with widely‐spaced microsatellite markers. Given this fact, it is valuable to identify markers under “suggestive linkage” with the trait (for e.g., [Tam et al, 2010]) as a starting point for future multilocus investigations. We considered all loci with LOD scores greater than 1.0 as demonstrating suggestive linkage.…”