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Previous studies have identified three loci (rs4737009, rs515071 and rs516946) in ankyrin 1 (ANK1) that are associated with type 2 diabetes mellitus (T2DM) in a number of ethnic groups. However, the impact of single nucleotide polymorphisms (SNPs) of ANK1 on T2DM in a Han Chinese population from northeast China has not yet been studied. The present study was undertaken to investigate the relationship between the ANK1 gene and new-onset T2DM in northeastern China. Three widely studied variants were genotyped and analyzed for T2DM susceptibility in 1,962 Chinese subjects (996 with T2DM and 966 healthy controls). Genotyping was performed using SNPscan™. The single-locus analysis, identified differences in the expression of rs515071 and rs516946 between cases and controls, with an odds ratio (OR) of 1.31 [95% confidence interval (CI), 1.10-1.55; P=0.002] and 1.32 (95% CI, 1.09-1.61; P=0.005) respectively, while there were no differences in the expression of rs4737009 between the groups. For the SNP of rs515071, the presence of AA or GA significantly reduced the risk of T2DM compared with GG (adjusted P=0.019, OR=0.78; 95% CI, 0.63-0.96). With respect to rs516946, individuals carrying TT or CT exhibited a decreased risk of T2DM compared with those with the CC allele (adjusted P=0.040, OR=0.79; 95% CI, 0.63-0.99). Furthermore, haplotype analysis indicated that the haplotype frequency of GC in T2DM cases was significantly higher than in controls (P=0.002, OR=1.31; 95% CI, 1.10-1.55). Furthermore, the rs516946-CC genotype was associated with a larger waist circumference (P=0.031). The present data indicated that ANK1 was a potential T2DM susceptibility gene in a Han Chinese population from northeastern China.

Association of ANK1 variants with new-onset type 2 diabetes in a Han Chinese population from northeast China