A Single Nucleotide Polymorphism within DUSP9 Is Associated with Susceptibility to Type 2 Diabetes in a Japanese Population

Hisashi Fukuda, Minako Imamura, Yasushi Tanaka, Minoru Iwata, Hiroshi Hirose, Kohei Kaku, Hiroshi Maegawa, Hirotaka Watada, Kazuyuki Tobe, Atsunori Kashiwagi, Ryuzo Kawamori, Shiro Maeda

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Abstract

Aims: The DUSP9 locus on chromosome X was identified as a susceptibility locus for type 2 diabetes in a meta-analysis of European genome-wide association studies (GWAS), and GWAS in South Asian populations identified 6 additional single nucleotide polymorphism (SNP) loci for type 2 diabetes. However, the association of these loci with type 2 diabetes have not been examined in the Japanese. We performed a replication study to investigate the association of these 7 susceptibility loci with type 2 diabetes in the Japanese population. Methods: We genotyped 11,319 Japanese participants (8,318 with type 2 diabetes and 3,001 controls) for each of the 7 SNPs-rs5945326 near DUSP9, rs3923113 near GRB14, rs16861329 in ST6GAL1, rs1802295 in VPS26A, rs7178572 in HMG20A, rs2028299 near AP3S2, and rs4812829 in HNF4A-and examined the association of each of these 7 SNPs with type 2 diabetes by using logistic regression analysis. Results: All SNPs had the same direction of effect (odds ratio [OR]>1.0) as in the original reports. One SNP, rs5945326 near DUSP9, was significantly associated with type 2 diabetes at a genome-wide significance level (p = 2.21×10-8; OR 1.39, 95% confidence interval [CI]: 1.24-1.56). The 6 SNPs derived from South Asian GWAS were not significantly associated with type 2 diabetes in the Japanese population by themselves (p≥0.007). However, a genetic risk score constructed from 6 South Asian GWAS derived SNPs was significantly associated with Japanese type 2 diabetes (p = 8.69×10-4, OR = 1.06. 95% CI; 1.03-1.10). Conclusions/interpretation: These results indicate that the DUSP9 locus is a common susceptibility locus for type 2 diabetes across different ethnicities, and 6 loci identified in South Asian GWAS also have significant effect on susceptibility to Japanese type 2 diabetes.

Original languageEnglish
Article numbere46263
JournalPloS one
Volume7
Issue number9
DOIs
Publication statusPublished - 2012 Sep 27

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Fukuda, H., Imamura, M., Tanaka, Y., Iwata, M., Hirose, H., Kaku, K., Maegawa, H., Watada, H., Tobe, K., Kashiwagi, A., Kawamori, R., & Maeda, S. (2012). A Single Nucleotide Polymorphism within DUSP9 Is Associated with Susceptibility to Type 2 Diabetes in a Japanese Population. PloS one, 7(9), [e46263]. https://doi.org/10.1371/journal.pone.0046263