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

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Medical problems
Polymorphism
noninsulin-dependent diabetes mellitus
Type 2 Diabetes Mellitus
single nucleotide polymorphism
Single Nucleotide Polymorphism
Nucleotides
Genome-Wide Association Study
Population
loci
Genes
odds ratio
Odds Ratio
confidence interval
Confidence Intervals
X Chromosome
X chromosome
Chromosomes
nationalities and ethnic groups
meta-analysis

ASJC Scopus subject areas

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

Cite this

A Single Nucleotide Polymorphism within DUSP9 Is Associated with Susceptibility to Type 2 Diabetes in a Japanese Population. / Fukuda, Hisashi; Imamura, Minako; Tanaka, Yasushi; Iwata, Minoru; Hirose, Hiroshi; Kaku, Kohei; Maegawa, Hiroshi; Watada, Hirotaka; Tobe, Kazuyuki; Kashiwagi, Atsunori; Kawamori, Ryuzo; Maeda, Shiro.

In: PLoS One, Vol. 7, No. 9, e46263, 27.09.2012.

Research output: Contribution to journalArticle

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, vol. 7, no. 9, e46263. https://doi.org/10.1371/journal.pone.0046263
Fukuda, Hisashi ; Imamura, Minako ; Tanaka, Yasushi ; Iwata, Minoru ; Hirose, Hiroshi ; Kaku, Kohei ; Maegawa, Hiroshi ; Watada, Hirotaka ; Tobe, Kazuyuki ; Kashiwagi, Atsunori ; Kawamori, Ryuzo ; Maeda, Shiro. / A Single Nucleotide Polymorphism within DUSP9 Is Associated with Susceptibility to Type 2 Diabetes in a Japanese Population. In: PLoS One. 2012 ; Vol. 7, No. 9.
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AU - Tanaka, Yasushi

AU - Iwata, Minoru

AU - Hirose, Hiroshi

AU - Kaku, Kohei

AU - Maegawa, Hiroshi

AU - Watada, Hirotaka

AU - Tobe, Kazuyuki

AU - Kashiwagi, Atsunori

AU - Kawamori, Ryuzo

AU - Maeda, Shiro

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