Association and interaction analyses of genetic variants in ADIPOQ, ENPP1, GHSR, PPARgamma and TCF7L2 genes for diabetic nephropathy in a Taiwanese population with type 2 diabetes.
BACKGROUND
Diabetic nephropathy (DN) is a common microvascular complication of diabetes. In this study, we aimed to explore both primary effects of single-locus and multilocus interactions to test the hypothesis that the type 2 diabetes (T2D) genes may contribute to the aetiology of DN in T2D independently and/or through complex interactions in a Taiwanese population with T2D.


METHODS
We genotyped six single nucleotide polymorphisms (SNPs) for five common T2D genes including adiponectin, C1Q and collagen domain containing (ADIPOQ), ectonucleotide pyrophosphatase/ phosphodiesterase 1 (ENPP1), growth hormone secretagogue receptor (GHSR), peroxisome proliferator-activated receptor gamma (PPARgamma) and transcription factor 7-like 2 (TCF7L2). There were 216 T2D patients diagnosed with DN and 178 age-similar T2D without DN (control) subjects. To investigate gene-gene interactions, we employed both generalized multifactor dimensionality reduction (GMDR) method and logistic regression models.


RESULTS
Single-locus analyses showed significant main effects of ENPP1 (P = 0.0032; adjusted OR = 1.85; 95% CI = 1.17-2.92) on the risk of DN in T2D. Furthermore, a potential gene-gene interaction involving ENPP1 and GHSR was suggested in the best two-locus GMDR model (P = 0.021). The significant three-locus GMDR model (P < 0.001) was also identified among ADIPOQ, GHSR and TCF7L2. Analyses using logistic regression models confirmed the gene-gene interactions.


CONCLUSIONS
The results suggest that the SNPs from the T2D-related genes may contribute to the risk of DN in T2D independently and/or in an interactive manner in Taiwanese T2D patients.
Wu
Lawrence Shih-Hsin
LS
1Vita Genomics, Inc, Wugu Shiang, Taipei, Taiwan.
Hsieh
Chang-Hsun
CH
Pei
Dee
D
Hung
Yi-Jen
YJ
Kuo
Shi-Wen
SW
Lin
Eugene
E
D052242:Adiponectin / Q000235:genetics; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000235:genetics*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*; D054440:Receptors, Ghrelin / Q000235:genetics*; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein
C499918:ADIPOQ protein, human; D052242:Adiponectin; D047495:PPAR gamma; D054440:Receptors, Ghrelin; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases