Gene-gene interactions among genetic variants from obesity candidate genes for nonobese and obese populations in type 2 diabetes.

Abstract

Recent studies indicate that obesity may play a key role in modulating genetic predispositions to type 2 diabetes (T2D). This study examines the main effects of both single-locus and multilocus interactions among genetic variants in Taiwanese obese and nonobese individuals to test the hypothesis that obesity-related genes may contribute to the etiology of T2D independently and/or through such complex interactions. We genotyped 11 single nucleotide polymorphisms for 10 obesity candidate genes including adrenergic beta-2-receptor surface, adrenergic beta-3-receptor surface, angiotensinogen, fat mass and obesity associated gene, guanine nucleotide binding protein beta polypeptide 3 (GNB3), interleukin 6 receptor, proprotein convertase subtilisin/kexin type 1 (PCSK1), uncoupling protein 1, uncoupling protein 2, and uncoupling protein 3. There were 389 patients diagnosed with T2D and 186 age- and sex-matched controls. Single-locus analyses showed significant main effects of the GNB3 and PCSK1 genes on the risk of T2D among the nonobese group (p = 0.002 and 0.047, respectively). Further, interactions involving GNB3 and PCSK1 were suggested among the nonobese population using the generalized multifactor dimensionality reduction method (p = 0.001). In addition, interactions among angiotensinogen, fat mass and obesity associated gene, GNB3, and uncoupling protein 3 genes were found in a significant four-locus generalized multifactor dimensionality reduction model among the obese population (p = 0.001). The results suggest that the single nucleotide polymorphisms from the obesity candidate genes may contribute to the risk of T2D independently and/or in an interactive manner according to the presence or absence of obesity.

• Authors: Eugene Lin, Dee Pei, Yi-Jen Huang, Chang-Hsun Hsieh, Lawrence Shih-Hsin Wu
• Journal: Genetic testing and molecular biomarkers (Genet Test Mol Biomarkers) Vol. 13 Issue 4 Pg. 485-93 (Aug 2009) ISSN: 1945-0257 [Electronic] United States
• PMID: 19594364 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• G-protein beta3 subunit
• Protein Subunits
• Proprotein Convertase 1
• Heterotrimeric GTP-Binding Proteins

Topics

• Adult
• Aged
• Body Mass Index
• Case-Control Studies
• Diabetes Mellitus, Type 2 (diagnosis, genetics)
• Female
• Genetic Predisposition to Disease (genetics)
• Genetic Variation
• Heterotrimeric GTP-Binding Proteins (genetics)
• Humans
• Male
• Middle Aged
• Obesity (diagnosis, genetics)
• Polymorphism, Single Nucleotide
• Proprotein Convertase 1 (genetics)
• Protein Subunits
• Taiwan