Abstract
AimWe performed a replication study in a Japanese population to evaluate the association between type 2 diabetes and 7 susceptibility loci originally identified by European genome-wide association study (GWAS) in 2012: ZMIZ1, KLHDC5, TLE1, ANKRD55, CILP2, MC4R, and BCAR1. We also examined the association of 3 additional loci: CCND2 and GIPR, identified in sex-differentiated analyses, and LAMA1, which was shown to be associated with non-obese European type 2 diabetes.MethodsWe genotyped 6,972 Japanese participants (4,280 type 2 diabetes patients and 2,692 controls) for each of the 10 single nucleotide polymorphisms (SNPs): rs12571751 in ZMIZ1, rs10842994 near KLHDC5, rs2796441 near TLE1, rs459193 near ANKRD55, rs10401969 in CILP2, rs12970134 near MC4R, rs7202877 near BCAR1, rs11063069 near CCND2, rs8108269 near GIPR, and rs8090011 in LAMA1 using a multiplex polymerase chain reaction invader assay. The association of each SNP locus with the disease was evaluated using a logistic regression analysis.ResultsAll SNPs examined in this study had the same direction of effect (odds ratio > 1.0, p = 9.77 × 10-4, binomial test), as in the original reports. Among them, rs12571751 in ZMIZ1 was significantly associated with type 2 diabetes [p = 0.0041, odds ratio = 1.123, 95% confidence interval 1.037–1.215, adjusted for sex, age and body mass index (BMI)], but we did not observe significant association of the remaining 9 SNP loci with type 2 diabetes in the present Japanese population (p ≥ 0.005). A genetic risk score, constructed from the sum of risk alleles for the 7 SNP loci identified by un-stratified analyses in the European GWAS meta-analysis were associated with type 2 diabetes in the present Japanese population (p = 2.3 × 10-4, adjusted for sex, age and BMI).Conclusions ZMIZ1 locus has a significant effect on conferring susceptibility to type 2 diabetes also in the Japanese population.
Highlights
Genetic susceptibility plays an important role in the development and/or progression of type 2 diabetes
Rs12571751 in ZMIZ1 was significantly associated with type 2 diabetes [p = 0.0041, odds ratio = 1.123, 95% confidence interval 1.037–1.215, adjusted for sex, age and body mass index (BMI)], but we did not observe significant association of the remaining 9 single nucleotide polymorphism (SNP) loci with type 2 diabetes in the present Japanese population (p ! 0.005)
A genetic risk score, constructed from the sum of risk alleles for the 7 SNP loci identified by un-stratified analyses in the European Genome-wide association studies (GWAS) metaanalysis were associated with type 2 diabetes in the present Japanese population (p = 2.3 × 10-4, adjusted for sex, age and BMI)
Summary
Genetic susceptibility plays an important role in the development and/or progression of type 2 diabetes. Genome-wide association studies (GWAS) for type 2 diabetes have been extensively conducted worldwide, and over 80 susceptibility loci have been identified [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19]. In a sex-differentiated analysis followed by a meta-analysis, rs11063069 near the cyclin D2 gene (CCND2) and rs8108269 near the gastric inhibitory polypeptide receptor gene (GIPR) were shown to be associated with type 2 diabetes with a genome-wide significance level, and the effect of CCND2 locus was stronger in male, whereas the association of the GIPR locus was more significant in female [16]. The remaining 10 SNP loci have not been well evaluated in the Japanese population, the association of 4 SNP loci (rs12571751, rs2796441, rs4591937 and rs7202877) with type 2 diabetes has been suggested [18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
