A single nucleotide polymorphism within DUSP9 is associated with susceptibility to type 2 diabetes in a Japanese population

• Published in: PloS one Vol. 7; no. 9; p. e46263
• Main Authors: Fukuda, Hisashi, Imamura, Minako, Tanaka, Yasushi, Iwata, Minoru, Hirose, Hiroshi, Kaku, Kohei, Maegawa, Hiroshi, Watada, Hirotaka, Tobe, Kazuyuki, Kashiwagi, Atsunori, Kawamori, Ryuzo, Maeda, Shiro
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.09.2012; Public Library of Science (PLoS)
• Subjects: Aged; Analysis; Asian Continental Ancestry Group; Biology; Case-Control Studies; Chromosomes, Human, X; Confidence intervals; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Disease susceptibility; Dual-Specificity Phosphatases - genetics; Endocrinology; European Continental Ancestry Group; Female; Genetic aspects; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomes; Hepatocyte nuclear factor 4; Humans; Insulin resistance; Internal medicine; Japan - epidemiology; Kinases; Laboratories; Loci; Male; Medicine; Metabolism; Middle Aged; Mitogen-Activated Protein Kinase Phosphatases - genetics; Molecular Typing; Obesity; Phosphatase; Physiological aspects; Polymorphism; Polymorphism, Single Nucleotide; Population; Proteins; Regression analysis; Risk; Risk factors; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Statistical analysis; Susceptibility; Type 2 diabetes; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0046263

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. 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. 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). 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.