Metabolic Syndrome Is Linked to Chromosome 7q21 and Associated With Genetic Variants in CD36 and GNAT3 in Mexican Americans

Metabolic abnormalities such as obesity, insulin resistance and hyperinsulinemia, impaired glucose tolerance, dyslipidemia, and hypertension often cluster to constitute the Metabolic Syndrome [MS]. The MS is a predictor of both type 2 diabetes (T2DM) and Coronary Heart Disease (CHD), and its prevalence has been rising alarmingly worldwide. In the United States (US), more than 47 million people are affected with MS. Specifically, its prevalence is high in minority populations such as Mexican Americans, who had the highest age-adjusted prevalence of MS [∼32%] when compared to the non-Hispanic whites, African Americans and other ethnic groups (1). Added to this burden, over the past 20 years, the prevalence of MS among children and adolescents has also been increasing at epidemic rates in several populations including Mexican Americans and African Americans (2-4). The MS and its components are complex disease conditions that are influenced by genetic and environmental factors and their interactions MS can be defined as a single, composite phenotype for genetic analysis using criteria such as the National Cholesterol Education Program [NCEP]/Adult Treatment Panel III [ATPIII] (NCEP/ATPIII) recommendations, the most widely used definition in the US (5,6). In addition to the NCEP/ATPIII criteria, several organizations have proposed different definitions for MS. While the various definitions use similar core components of MS, primarily including the measurements of obesity, glucose, lipids, and blood pressure, they differ in the number of traits and the cut-off points required for the diagnosis. Despite certain caveats, several studies have used the NCEP/ATPIII definition for its simplicity, in the context of clinical practice and epidemiological investigations (7); most importantly, as noted by Grundy et al. (6), it avoids emphasis on a single cause. Several genome-wide linkage and association studies have been performed to understand the genetic basis of the components of MS by using a number of analytical tools such as multivariate genetic analysis and factor analysis (8-12). Such studies have identified several genetic regions linked to MS related traits, but showing limited concordance in their results (11). In contrast to the above approaches, a single, composite MS phenotype using the NCEP/ATPIII or other criteria can be used to identify genetic regions with potential common genetic influences on MS; however, there have been a few such studies (13, 14). Therefore, the aim of our study was to identify the susceptibility loci for MS using the NCEP/ATPIII definition in a Mexican American population who are at high risk for the development of MS. Here, we report the results of our genome-wide linkage screen for MS performed by using the multipoint variance components linkage analysis and the phenotypic and genotypic (∼10 cM map) data collected from the Mexican American individuals who participated in our San Antonio Family Diabetes/Gallbladder Study (SAFDGS). In addition, we report the results of our preliminary MS association study performed by examining the genetic variants in two of the positional candidate genes, which are physically close to each other, located within the 1-LOD support interval region of our MS linkage signal on chromosome 7q.