title: Association of a cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) polymorphism with elevated hemoglobin A₁(c) levels and the prevalence of metabolic syndrome in Japanese men: interaction with dietary energy intake.
abstract: Genome-wide association studies have identified the cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) gene as a novel risk factor for type 2 diabetes mellitus. Application of this genetic marker for prevention of type 2 diabetes and metabolic syndrome (MetS) in healthy populations has not yet been evaluated. The authors examined the effects of a CDKAL1 polymorphism (rs9465871) on metabolic phenotype and of gene-lifestyle (CDKAL1-energy intake) interaction on MetS in a cohort of apparently healthy Japanese men examined in 2003. The CC genotype of the CDKAL1 variant was associated with elevated glycosylated hemoglobin A₁(c) (HbA1c) levels. The prevalence of MetS was 25.6% for CC and 16.3% for TT + CT (odds ratio = 2.18, 95% confidence interval: 1.06, 4.48; P = 0.035). When dietary energy intake was accounted for, the variant's effect on HbA1c was observed in the highest energy-intake group (mean: CC, 5.6% (standard deviation, 1.7); TT + CT, 5.0% (standard deviation, 0.5); P = 0.025). In addition, the positive association between HbA1c and energy intake was stronger in subjects with the CC genotype than in subjects with TT + CT. These results suggest that the interaction between the CDKAL1 polymorphism and dietary energy intake influences the dysglycemic phenotype leading to MetS, possibly through impaired insulin secretion. The CDKAL1 polymorphism may be a marker for MetS in the Japanese population.
authors.affiliation: Department of Neurology, Keio University, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyaki
authors.forename: Than
authors.initials: T
authors.lastname: Oo
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Song
authors.forename: Htay
authors.initials: H
authors.lastname: Lwin
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tomita
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Hoshino
authors.forename: Norihiro
authors.initials: N
authors.lastname: Suzuki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Muramatsu
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D002149:Energy Intake; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000178:diet therapy* / Q000208:ethnology / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015995:Prevalence; D012307:Risk Factors; D012359:tRNA Methyltransferases
chemical_list: D051360:Cyclin-Dependent Kinase 5; D005819:Genetic Markers; D006442:Glycated Hemoglobin; D012359:tRNA Methyltransferases; C525110:CDKAL1 protein, human