Association of insulin sensitivity and glucose tolerance with the c.825C>T variant of the G protein beta-3 subunit gene

Abstract

The risk of macrovascular complications of diabetes mellitus is greatly enhanced by the presence of high blood pressure. In addition, hypertension and diabetes share insulin resistance as a common pathophysiological mechanism. Despite evidence for a common molecular genetic background of insulin resistance, glucose intolerance and hypertension, few candidate genes have been shown to influence all of these features simultaneously. We examined the association of insulin sensitivity with the c.825C>T variant of the g-protein beta-3 subunit (GNB3), a candidate gene of hypertension, in families of Mexican American hypertensive patients.Methods-180 subjects enrolled in a family study of Mexican American hypertensive patients were recruited from hypertension clinics in Los Angeles. Subjects underwent pre-treatment blood pressure recording, an oral glucose tolerance test, euglycemic, hyperinsulinemic clamp and anthropometric measurements. DNA from peripheral blood leukocytes was genotyped by PCR and restriction enzyme digest with BseD I (GNB). Statistical analysis was performed by transmission disequilibrium testing.Results-In carriers of the T-allele, blood glucose was significantly lower (fasting: 96.7 ± 22.9 vs. 106.7 ± 51.7mg/dl, p = 0.009, oGTT 120 min: 131.7 ± 48.7 vs. 137.8 ± 64.9 mg/dl, p = 0.036; mean ± SD) and insulin sensitivity significantly higher (229.0 ± 108.7 vs. 188.5 ± 94.2 mg/kg/min, p = 0.037) than in homozygous carriers of the C-allele. Blood pressure did not differ significantly between the phenotypes. Conclusion-In a MexicanAmerican hypertensive population, we found evidence for higher insulin sensitivity in carriers of the T allele of the c.825C>T variant of GNB3.

Effects of C825T polymorphism of the GNB3 gene on availability of dopamine transporter in healthy volunteers — A SPECT study

“…The SNP C825T of the GNβ3 gene has been reported to be associated with elevated metabolic indexes in different groups of patients suffering from hypertension, diabetes or cardiovascular disease (Brand et al, 2003;Casiglia et al, 2008;Danoviz et al, 2006;Hayakawa et al, 2007;Kopf et al, 2008;Meirhaeghe et al, 2005). Moreover, the variant has also been found to be associated with medication-induced metabolic disturbances (Hauner et al, 2003;Peters et al, 2008;Souza et al, 2008;Wang et al, 2005).…”

Sherlock: Detecting Gene-Disease Associations by Matching Patterns of Expression QTL and GWAS

“…46 In addition, a closely related gene, GNB3 (MIM 139130), is shown to be associated with obesity, insulin resistance, and glucose tolerance in several studies. 47 A SNP close to JAZF1 (MIM 606246) was associated with T2D, 44,48 and deletion of Jazf1 in mice leads to increased fat mass and insulin resistance. 49 Interestingly, the SNP rs849134 (close to the supporting cis eSNP rs1635852 of JAZF1, Table 4) was reported to be strongly associated with both T2D and the expression of JAZF1 in adipose tissue in the DIAGRAM study.…”

Directed Causal Network Construction Using Linkage Analysis with Metabolic Syndrome-Related Expression Quantitative Traits

“…Genetic studies on metabolic syndrome have been conducted mostly using the candidate gene approach, with much success in identifying its genetic components (Bonnet et al, 2008;Groop, 2000;Horenstein and Shuldiner, 2004;Ma et al, 2007;Mercado et al, 2002;Sale et al, 2006;Stern, 2003;Vasseur et al, 2006;Wang et al, 2004;Yang and Chuang, 2006). Some studies have focused on the relationships between components of the metabolic syndrome (Kopf et al, 2008;Mussig et al, 2009) or among the candidate genes that are related to it (Foufelle and Ferre, 2002). However, the mechanism that underlies the interrelationships between related genes has been not fully determined, and although various genes contribute to the disease, the effect size of a single gene is very weak.…”