Genetic variants at CDC123/CAMK1D and SPRY2 are associated with susceptibility to type 2 diabetes in the Japanese population

• Published in: Diabetologia 2011-12, Vol.54 (12), p.3071-3077
• Main Authors: Imamura, M., Iwata, M., Maegawa, H., Watada, H., Hirose, H., Tanaka, Y., Tobe, K., Kaku, K., Kashiwagi, A., Kawamori, R., Nakamura, Y., Maeda, S.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Asian Continental Ancestry Group - genetics; Asian Continental Ancestry Group - statistics & numerical data; Biological and medical sciences; Blood Glucose - genetics; Blood Glucose - metabolism; Calcium-Calmodulin-Dependent Protein Kinase Type 1 - genetics; Cell Cycle Proteins - genetics; Diabetes; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinology; Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fasting; Fasting - metabolism; Female; Gene loci; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Genetic testing; Genetic Variation; Genome-Wide Association Study; Genomes; Health risk assessment; Human Physiology; Humans; Insulin resistance; Insulin Resistance - genetics; Internal Medicine; Intracellular Signaling Peptides and Proteins - genetics; Male; Medical sciences; Medicine; Medicine & Public Health; Membrane Proteins; Metabolic Diseases; Metabolism; Middle Aged; Outpatient care facilities; Polymorphism, Single Nucleotide
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-011-2293-3

Aims/hypothesis Recently, rs10906115 in CDC123/CAMK1D , rs1359790 near SPRY2 , rs1436955 in C2CD4A/C2CD4B and rs10751301 in ODZ4 were identified as genetic risk variants for type 2 diabetes by a genome-wide association study in a Chinese population. The aim of the present study was to ascertain the role of these four variants in conferring susceptibility to type 2 diabetes in the Japanese population. Methods We genotyped 11,530 Japanese individuals (8,552 type 2 diabetes cases, 2,978 controls) for the above single nucleotide polymorphisms (SNPs) and used logistic regression analysis to determine whether they were associated with type 2 diabetes. Results In accordance with the findings in a Chinese population, rs10906115 A, rs1359790 C and rs1436955 G were found to be risk alleles. Both rs10906115 and rs1359790 were significantly associated with susceptibility to type 2 diabetes in our study (rs10906115 OR 1.15, 95% CI 1.08, 1.22; p  = 6.10 × 10 −6 ; rs1359790 OR 1.14, 95% CI 1.06, 1.21; p  = 2.24 × 10 −4 ). Adjustment for age, sex and BMI had no significant effects on the association between these variants and the disease. We did not observe any significant associations between the SNPs and any metabolic traits, e.g. BMI, fasting plasma glucose (determined for 1,332 controls), HOMA of beta cell function (900 controls) and HOMA of insulin resistance (900 controls; p  > 0.05). Conclusions/interpretation The SNPs rs10906115 A and rs1359790 C are significantly associated with susceptibility to type 2 diabetes in the Japanese population, confirming that these alleles are common susceptibility variants for type 2 diabetes in East Asian populations.