Association between polymorphisms of the alpha-kinase 1 gene and type 2 diabetes mellitus in community-dwelling individuals

We previously demonstrated that the a-kinase 1 gene (ALPK1) is a susceptibility locus for chronic kidney disease in individuals with diabetes mellitus (DM) by a genome-wide association study. Although genetic variants of ALPK1 have been associated with chronic kidney disease in individuals with DM, whether ALPK1 is a susceptibility locus for DM has not been elucidated. The purpose of the present study was to investigate a possible association of the rs2074388 (A -> G, Asp565Gly) or rs2074379 (A -> G, Ile732Met) variants of ALPK1 with type 2 DM in community-dwelling individuals. The study subjects comprised 5,959 community-dwelling individuals (495 subjects with type 2 DM and 5,464 controls) who were recruited to a population-based cohort study in Inabe, Mie, Japan. The comparisons of allele frequencies or genotype distributions using the Chi-square test revealed that the rs2074388 and rs2074379 variants of ALPK1 were significantly associated with type 2 DM (P< 0.05). A multivariable logistic regression analysis with adjustment for age, gender, body mass index and smoking status revealed that the rs2074388 (P= 0.0051; odds ratio, 1.32) and rs2074379 (P= 0.0058; odds ratio, 1.32) variants were significantly associated with type 2 DM. The haplotype analysis of these polymorphisms revealed that the frequency of the major haplotype, A (rs2074388) -A (rs2074379), was significantly lower, whereas that of the minor haplotype G-G was significantly higher in subjects with type 2 DM compared to controls. Thus, ALPK1 may be a susceptible gene for type 2 DM in community-dwelling Japanese individuals.