Association of a cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) polymorphism with elevated hemoglobin Alc levels and the prevalence of metabolic syndrome in Japanese men

Interaction with dietary energy intake

Koichi Miyaki, Than Oo, Yixuan Song, Htay Lwin, Yutaka Tomita, Haruhiko Hoshino, Norihiro Suzuki, Masaaki Muramatsu

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 A1c (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.

Original languageEnglish
Pages (from-to)985-991
Number of pages7
JournalAmerican Journal of Epidemiology
Volume172
Issue number9
DOIs
Publication statusPublished - 2010 Nov 1

Fingerprint

Cyclin-Dependent Kinase 5
Protein Subunits
Energy Intake
Hemoglobins
Type 2 Diabetes Mellitus
Genotype
Phenotype
Genome-Wide Association Study
Glycosylated Hemoglobin A
Genetic Markers
Population
Genes
Life Style
Odds Ratio
Confidence Intervals
Insulin

Keywords

  • CDKAL1 protein, human
  • energy intake
  • hemoglobin A1c protein, human
  • Japan
  • metabolic syndrome X

ASJC Scopus subject areas

  • Epidemiology

Cite this

Association of a cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) polymorphism with elevated hemoglobin Alc levels and the prevalence of metabolic syndrome in Japanese men : Interaction with dietary energy intake. / Miyaki, Koichi; Oo, Than; Song, Yixuan; Lwin, Htay; Tomita, Yutaka; Hoshino, Haruhiko; Suzuki, Norihiro; Muramatsu, Masaaki.

In: American Journal of Epidemiology, Vol. 172, No. 9, 01.11.2010, p. 985-991.

Research output: Contribution to journalArticle

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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 A1c (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.",
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