Association of glycosylated hemoglobin with the gene encoding CDKAL1 in the Korean Association Resource (KARE) study

Genome-wide associations with glycosylated hemoglobin, which reflects the long-term glycemia, were examined using two independent cohorts of the Korea Association Resource (KARE) consortium. We first identified sequence variants within a linkage disequilibrium block (r(2) > 0.98) in the intron 5 of cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) gene using 4,275 normoglycemic subjects of Cohort 1 (P < 2.5 × 10(-8)). The association was replicated in 3,782 normoglycemic subjects of Cohort 2. Furthermore, the sequence variants were also associated with glucose levels after oral glucose tolerance test. Especially, a strong association with 1 h glucose (P = 1.3 × 10(-11)) led us to interpreting that CDKAL1 might influence the level of glycosylated hemoglobin by affecting 1 h glucose level. Ultimately, accumulated effects on the glycosylated hemoglobin level by the genetic variation of CDKAL1 might affect susceptibility to type 2 diabetes mellitus.