Joint effect of CENTD2 and KCNQ1 polymorphisms on the risk of type 2 diabetes mellitus among Chinese Han population.
Genome-wide association studies (GWAS) in populations of European ancestry have identified nine single nuclear polymorphisms (SNP) on chromosome 11 related to type 2 diabetes (T2D) susceptibility. Herein, we further evaluate the association of these SNPs and T2D in a Chinese Han population. We performed a case-control study of 2925 T2D cases and 3281 controls to evaluate the association of five SNPs of KCNJ11, MTNR1B, CENTD2 and LOC387761 and T2D in addition to the previously reported four SNPs of KCNQ1. Multiple logistic regression was used to evaluate SNP's effect by adjustment for confounding factor age, sex and BMI. In the first stage, SNPs rs1552224 at CENTD2 were significantly associated with T2D and the association was statistically significant in the whole study population (P = 0.001) although it was not replicated in the second stage. rs1552224 and rs2237897 of KCNQ1 showed significant joint effect on T2D and there was a significant decreased risk of T2D with the number increase of risk alleles (P for trend = 3.81 × 10(-17)). Compared to those without carrying any risk allele, individuals carrying one, two, and three or four risk alleles had a 30.7%, 44.8% and 62.0% decreased risk for developing T2D, respectively. Our finding suggests that genetic variant rs1552224 of CENTD2 on chromosome 11 contributes to an independent effect as well as joint cumulative effect with rs2237897 of KCNQ1 on the risk of T2D in Chinese Han population, and further functional research would be warranted.
Department of Chronic Non-communicable Disease Control, Wuxi Center for Disease Control and Prevention, Wuxi 214023, China.
Yun
Y
Qian
Department of Chronic Non-communicable Disease Control, Wuxi Center for Disease Control and Prevention, Wuxi 214023, China.
Meihua
M
Dong
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Feng
F
Lu
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Huizhang
H
Li
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Guangfu
G
Jin
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Zhibin
Z
Hu
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address: sc100@126.com.
Chong
C
Shen
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Hongbing
H
Shen
D000368:Aged; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D044123:Receptor, Melatonin, MT2 / Q000235:genetics; D012306:Risk; D011795:Surveys and Questionnaires; D000099161:Kcnj11 Channel
D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D051657:KCNQ1 Potassium Channel; D024661:Potassium Channels, Inwardly Rectifying; D044123:Receptor, Melatonin, MT2; D000099161:Kcnj11 Channel; C446513:ARAP1 protein, human; C496909:KCNQ1 protein, human; C573871:MTNR1B protein, human
Association study; CENTD2; Chromosome 11; KCNQ1; Type 2 diabetes