| 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
(Affiliation: Bioinformatics Division, Vita Genomics, Inc., Taipei County, Taiwan.)
|
| 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
|
