Association of genetic variants for susceptibility to obesity with type 2 diabetes in Japanese individuals

Diabetologia. 2011 Jun;54(6):1350-9. doi: 10.1007/s00125-011-2086-8. Epub 2011 Mar 3.

Abstract

Aims/hypothesis: In populations of East Asian descent, we performed a replication study of loci previously identified in populations of European descent as being associated with obesity measures such as BMI and type 2 diabetes.

Methods: We genotyped 14 single nucleotide polymorphisms (SNPs) from 13 candidate loci that had previously been identified by genome-wide association meta-analyses for obesity measures in Europeans. Genotyping was done in 18,264 participants from two general Japanese populations. For SNPs showing an obesity association in Japanese individuals, we further examined diabetes associations in up to 6,781 cases and 7,307 controls from a subset of the original, as well as from additional populations.

Results: Significant obesity associations (p < 0.1 two-tailed, concordant direction with previous reports) were replicated for 11 SNPs from the following ten loci in Japanese participants: SEC16B, TMEM18, GNPDA2, BDNF, MTCH2, BCDIN3D-FAIM2, SH2B1-ATP2A1, FTO, MC4R and KCTD15. The strongest effect was observed at TMEM18 rs4854344 (p = 7.1 × 10(-7) for BMI). Among the 11 SNPs showing significant obesity association, six were also associated with diabetes (OR 1.05-1.17; p = 0.04-2.4 × 10(-7)) after adjustment for BMI in the Japanese. When meta-analysed with data from the previous reports, the BMI-adjusted diabetes association was found to be highly significant for the FTO locus in East Asians (OR 1.13; 95% CI 1.09-1.18; p = 7.8 × 10(-10)) with substantial inter-ethnic heterogeneity (p = 0.003).

Conclusions/interpretation: We confirmed that ten candidate loci are associated with obesity measures in the general Japanese populations. Six (of ten) loci exert diabetogenic effects in the Japanese, although relatively modest in size, and independently of increased adiposity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asian Continental Ancestry Group / ethnology
  • Asian Continental Ancestry Group / genetics*
  • Body Mass Index
  • Brain-Derived Neurotrophic Factor / genetics
  • Case-Control Studies
  • Comorbidity
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Japan
  • Male
  • Membrane Proteins / genetics
  • Membrane Transport Proteins / genetics
  • Middle Aged
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Proteins / genetics
  • Obesity / epidemiology*
  • Obesity / ethnology
  • Obesity / genetics*
  • Polymorphism, Single Nucleotide / genetics*

Substances

  • Brain-Derived Neurotrophic Factor
  • MTCH2 protein, human
  • Membrane Proteins
  • Membrane Transport Proteins
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Proteins
  • TMEM18 protein, human