Association of genetic variants of the α-kinase 1 gene with myocardial infarction in community-dwelling individuals

Abstract

We previously demonstrated that rs2074380 (G→A, Gly870Ser) and rs2074381 (A→G, Asn916Asp) of the α-kinase 1 gene (ALPK1) were significantly associated with chronic kidney disease (CKD) in individuals with diabetes mellitus. As CKD is a significant risk factor for coronary heart disease, we hypothesized that rs2074380 and rs2074381 of ALPK1 may contribute to the genetic susceptibility to myocardial infarction (MI) through affecting the susceptibility to CKD. The aim of the present study was to investigate a possible association of rs2074380 and rs2074381 with MI in community-dwelling individuals. The study subjects comprised 5,771 community-dwelling individuals (41 subjects with MI and 5,730 controls) who were recruited to a population-based cohort study in Inabe, Japan. The comparison of allele frequencies and genotype distributions using the Chi-square test revealed that rs2074380 and rs2074381 were significantly associated with MI (P<0.05). The multivariable logistic regression analysis with adjustment for covariates demonstrated that rs2074380 (P=0.0354, dominant model) and rs2074381 (P=0.0438, dominant model) were significantly associated with MI, with the minor A and G alleles, respectively, being protective against this condition. A haplotype analysis of these polymorphisms indicated that the frequency of the major haplotype, G (rs2074380)-A (rs2074381), was significantly higher (permutation P=0.012), whereas that of the minor haplotype A-G was significantly lower (P=0.020), in subjects with MI compared to that observed among controls. Therefore, ALPK1 may be a susceptible locus for MI.