Showing papers by "Anny H. Xiang published in 2008"

Evidence of Interaction Between PPARG2 and HNF4A Contributing to Variation in Insulin Sensitivity in Mexican Americans

Abstract: OBJECTIVE— We hypothesized that interaction between PPARG2 Pro12Ala and variants in the promoter region of HNF4A are associated with type 2 diabetes–related quantitative traits in Mexican-American families of a proband with previous gestational diabetes. RESEARCH DESIGN AND METHODS— The BetaGene project genotyped PPARG2 Pro12Ala and nine HNF4A single nucleotide polymorphisms (SNPs) in 473 individuals in 89 families. Members of the proband generation had fasting glucose RESULTS— Neither PPARG2 Pro12Ala nor any of the nine HNF4A SNPs were independently associated with type 2 diabetes–related quantitative traits. However, the interaction between PPARG2 Pro12Ala and HNF4A rs2144908 was significantly associated with both insulin sensitivity ( S I ) (Bonferroni P = 0.0006) and 2-h insulin (Bonferroni P = 0.039). Subjects with at least one PPARG2 Ala allele and homozygous for the HNF4A rs2144908 A allele had 40% higher S I compared with individuals with at least one G allele. S I did not vary by rs2144908 genotype among PPARG2 Pro/Pro. The interaction result for S I was replicated by the Insulin Resistance Atherosclerosis Family Study ( P = 0.018) in their San Antonio sample ( n = 484) where subjects with at least one PPARG2 Ala allele and homozygous for the HNF4A rs2144908 A allele had a 29% higher S I compared with individuals with at least one G allele. However, the interaction was not replicated in their San Luis Valley sample ( n = 496; P = 0.401). CONCLUSIONS— Together, these results suggest that variation in PPARG2 and HNF4A may interact to regulate insulin sensitivity in Mexican Americans at risk for type 2 diabetes.

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 c825C>T variant of the g-protein beta-3 subunit (GNB3), a candidate gene of hypertension, in families of Mexican-American hypertensive patients Methods One hundred eighty subjects enrolled in a family study of Mexican-American hypertensive patients were recruited from hypertension clinics in Los Angeles Subjects underwent pretreatment blood pressure recording, an oral glucose tolerance test, euglycemic hyperinsulinemic clamp, and anthropometric measurements DNA from peripheral blood leukocytes was genotyped by polymerase chain reaction and restriction enzyme digest with BseD1 (GNB) Statistical analysis was performed by transmission disequilibrium testing Results In carriers of the T-allele, blood glucose was significantly lower [(mean+SD) fasting: 967+229 vs 1067+517mg/dl, P =009; oral glucose tolerance test (oGTT) 120 min: 1317+487 vs 1378+649 mg/dl, P =036], and insulin sensitivity was significantly higher (2290+1087 vs 1885+942 mg/kg per minute, P =037) than in homozygous carriers of the C-allele Blood pressure did not differ significantly between the phenotypes Conclusion In a Mexican-American hypertensive population, we found evidence for higher insulin sensitivity in carriers of the T allele of the c825C>T variant of GNB3