Abstract 10462: Association of a Polymorphism of BTN2A1 With Type 2 Diabetes Mellitus in Japanese Individuals
Introduction: Diabetes mellitus (DM) is an important risk factor for coronary heart disease. Although recent genetic studies suggested that several genetic variants increase the risk for type 2 DM in Caucasian individuals, the genes that underlie genetic susceptibility to this condition in Asian populations remain to be identified definitively. We previously showed that the C→T polymorphism (rs6929846) in the promoter region of BTN2A1 was significantly associated with myocardial infarction in Japanese individuals by a genome-wide association study.
Hypothesis: We assessed the hypothesis that the association of rs6929846 of BTN2A1 with myocardial infarction might be attributable, at least in part, to its effects on susceptibility to type 2 DM.
Methods: A total of 8650 Japanese individuals from two independent subject panels were examined: Subject panel A comprised 1141 individuals with type 2 DM and 3161 controls; and subject panel B comprised 1664 individuals with type 2 DM and 2684 controls.
Results and Conclusions: The chi-square test revealed that rs6929846 of BTN2A1 was significantly related to the prevalence of type 2 DM in subject panels A (P = 0.0002) and B (P = 0.0059). Multivariable logistic regression analysis with adjustment for covariates revealed that rs6929846 was significantly associated with type 2 DM in subject panel A (P = 0.0407; odds ratio, 1.23) and in subject panel B (P = 0.0054; odds ratio, 1.28), with the T allele representing a risk factor for this condition. The rs6929846 was significantly associated with fasting plasma glucose levels in subject panels A (P = 0.0076) and in all subjects (P = 0.0033) and with blood glycosylated hemoglobin content in subject panel B (P = 6.7 × 10−6) and in all subjects (P = 8.5 × 10−5), with the T allele being related to increased levels of both parameters. The risk T allele of rs6929846 was associated with increases in transcription activity of BTN2A1 as well as in the serum concentration of high sensitivity C-reactive protein, suggesting that the T allele of rs6929846 may accelerate inflammatory process. In conclusion, BTN2A1 may be a susceptibility gene for type 2 DM in Japanese individuals. Determination of genotype for this polymorphism may prove informative for assessment of the genetic risk for type DM.
- © 2010 by American Heart Association, Inc.