Genetic Associations with Metabolic Syndrome and Its Quantitative Traits by Race/Ethnicity in the United States

Abstract

Background: Elevated insulin resistance (IR), triglycerides (TG), body mass index (BMI), and waist circumference (WC) are features of the metabolic syndrome. Although several single-nucleotide polymorphisms (SNPs) associated with these traits have been reported, no study has reported their risk allele frequencies and effect sizes among the major U.S. race/ethnic groups in a nationally representative sample. Methods: We compared the risk allele frequencies of eight SNPs previously associated with IR, TG, BMI, or WC by race/ethnicity (non-Hispanic white, non-Hispanic black, Mexican American) in 3,030 participants of the National Health and Nutrition Examination Study III (NHANES III). In regression models predicting IR, TG, BMI, WC, and metabolic syndrome, we tested whether the SNP effect sizes on these traits varied by race/ ethnicity. Results: Risk allele frequencies varied by race/ethnicity for all eight loci (P < 0.0001). The directionality of effects of the variants on IR, TG, WC, and BMI was generally consistent with previous observations and did not differ by race/ethnicity (P > 0.001), although our study had low power for this test. No SNP predicted metabolic syndrome in any of the three groups (P > 0.05). Conclusions: The significance of racial/ethnic differences in risk allele frequencies merits consideration if genetic discoveries are to have clinical and public health applicability.

Single nucleotide polymorphisms (SNPs) involved in insulin resistance, weight regulation, lipid metabolism and inflammation in relation to metabolic syndrome: an epidemiological study

“…Besides IRS1 rs2943634 the group of insulin resistance SNPs consisted of PPARG rs1801282, GCKR rs780094, GCK rs1799884, and IGF1 rs35767. In line with other studies, none of these SNPs were associated with MetS in our data [4,37,38]. This may be explained by the relatively weak effect on HOMA-IR of PPARG rs1801282, GCK rs1799884, and IGF1 rs35767 [14,15] or by pleiotropic effects of PPARG rs1801282 and GCKR rs780094.…”

“…Furthermore, in human studies IRS1 rs2943634 has been associate with glucose related [15] and lipid traits [36]. In contrast, in a study among 1126 non-Hispanic whites, 898 non-Hispanic blacks and 906 Mexican Americans, IRS1 rs7578326 ( r 2 with rs2943634=0.82) was not associated with MetS, neither in the overall population, nor in specific ethnic groups [37]. However, as the number of Caucasian participants and MetS prevalence were lower than in our study, the former study may have been underpowered in Caucasian.…”

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

“…The relationship between diabetes and CAV1 deficiency has been studied mainly in animal models; thus, our novel finding in humans requires future validation [30, 33]. The reasons underlying the apparent higher odds for MetS and diabetes in Caucasian vs. Hispanic carriers of the CAV1 variant are unclear, and future studies are needed to explore whether this difference is due to variations in allele frequency/race/ethnicity or to dissimilarities in the cohort characteristics [34]. …”

Is Genetic testing useful to predict type 2 diabetes?

“…It is well known that the risk allele frequencies for many cardiometabolic traits vary by race and ethnicity. 63–65 However, genetic association studies are generally finding that T2D-associated variants from European GWAS have similar effects in non-European populations. 66 Still, the European T2D-associated SNPs are likely much poorer proxies for the true causal variants in older ancestral populations such as Africans, which have more fragmented genomic LD.…”