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

We previously demonstrated that the α‑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.