Association study of genetic variants of 17 diabetes-related genes/loci and cardiovascular risk and diabetic nephropathy in the Chinese She population (中国畲族人群17个糖尿病相关基因位点的遗传变异与心血管风险和糖尿病肾病的相关性)

• Published in: Journal of diabetes Vol. 5; no. 2; pp. 136 - 145
• Main Authors: Chen, Gang, Xu, Yuan, Lin, Yinghua, Lai, Xiaolan, Yao, Jin, Huang, Baoying, Chen, Zichun, Huang, Huibin, Fu, Xianguo, Lin, Lixiang, Lai, Shenghan, Wen, Junping
• Format: Journal Article
• Language: English
• Published: Australia Blackwell Publishing Ltd 01.06.2013; John Wiley & Sons, Inc
• Subjects: Alleles; Asian Continental Ancestry Group; Cardiovascular Diseases - ethnology; Cardiovascular Diseases - genetics; Diabetes Mellitus, Type 2 - ethnology; Diabetes Mellitus, Type 2 - genetics; Diabetic Nephropathies - ethnology; Diabetic Nephropathies - genetics; estimated glomerular filtration rate; Genetic Association Studies; Genetic Loci; Genetic Predisposition to Disease; Genetic Variation; Genotype; Humans; Minnesota Code; Polymorphism, Single Nucleotide; Risk Factors; single nucleotide polymorphism; Type 2 diabetes mellitus; 估算肾小球滤过率，明尼苏达编码，单核苷酸多态性，2型糖尿病
• ISSN: 1753-0393; 1753-0407; 1753-0407
• DOI: 10.1111/1753-0407.12025

Background Genetic determinations are important in type 2 diabetes (T2DM) pathology. We investigated associations between genetic variants of 17 diabetes‐related genes/loci, T2DM and diabetic complications in Chinese She subjects. Methods A comprehensive gene‐based association study was conducted using 17 single nucleotide polymorphisms in Chinese She subjects with normal glucose tolerance (n = 1119), impaired glucose regulation (n = 1767), and T2DM (n = 443). We applied major abnormal Minnesota Code findings to predict cardiovascular risk and estimated glomerular filtration rate to assess kidney function. Results Nine variants in FTO rs8050136, WFS1 rs10010131, CDKN2A/B rs10811661, KCNJ11 rs5219, CDC123/CAMK1D rs12779790, JAZF1 rs864745, SLC30A8 rs13266634, CDKAL1 rs10946398, and HHEX/IDE rs5015480 were significantly associated with T2DM (P < 0.05). Single nucleotide polymorphisms in WFS1 rs10010131, CDKN2A/B rs10811661, CDC123/CAMK1D rs12779790, JAZF1 rs864745, FTO rs8050136, and HHEX/IDE rs5015480 were associated with T2DM and impaired glucose regulation. Risk alleles in WFS1 rs10010131, IGF2BP2 rs4402960, CDKAL1 rs10946398, FTO rs8050136, KCNQ1 rs2237897, and ADAMTS9 rs4607103 were significantly associated with decreased homeostatic model assessment (HOMA)‐β (P < 0.05). After adjusting for age, gender and body mass index, genetic variants JAZF1 rs864745, FTO rs8050136, and HHEX/IDE rs5015480 were significantly related to reduced estimated glomerular filtration rate (P < 0.05). Genetic variants in WFS1 rs10010131, CDKN2A/B rs10811661, CDC123/CAMID rs12779790, JAZF1 rs864745, FTO rs80501360, CDKAL1 rs10946398, and HHEX/IDE rs5015480 correlated with abnormal major Minnesota Code findings (P < 0.05). Conclusion Variants in WFS1, CDKN2A/B, KCNJ11, CDC123/CAMK1D, JAZF1, SLC30A8, FTO, CDKAL1, and HHEX/IDE genes are significantly associated with T2DM in She Chinese subjects. JAZF1, FTO, CDKAL1, and HHEX/IDE are associated with diabetic nephropathy. WFS1, CDKN2A/B, CDC123/CAMK1D, JAZF1, FTO, CDKAL1, and HHEX/IDE are associated with cardiovascular risk. 摘要 背景 遗传是决定2型糖尿病发病的重要因素。我们分析了中国畲族人群17个糖尿病相关基因位点的遗传变异与2型糖尿病及并发症之间的相关性。 方法 一项全面的以基因为基础的相关性研究，评估了中国畲族人群的糖耐量正常者（n=1119）、糖耐量异常者（n=1767）和2型糖尿病患者（n=443）的17个基因的单核苷酸多态性（SNP）。以主要的明尼苏达编码异常预测心血管风险，用估算肾小球滤过率评估肾功能。 结果 FTO rs8050136，WFS1 rs10010131，CDKN2A/B rs10811661，KCNJ11 rs5219，CDC123/CAMK1D rs12779790，JAZF1 rs864745，SLC30A8 rs13266634，CDKAL1 rs10946398，和HHEX/IDE rs5015480等9个基因位点变异与2型糖尿病显著相关 （P<0.05）。WFS1 rs10010131，CDKN2A/B rs10811661，CDC123/CAMK1D rs12779790，JAZF1 rs864745，FTO rs8050136和HHEX/IDE rs5015480等的SNP与2型糖尿病和糖耐量异常相关。WFS1 rs10010131，IGF2BP2 rs4402960，CDKAL1 rs10946398，FTO rs8050136，KCNQ1 rs2237897和 ADAMTS9 rs4607103等的风险等位基因与HOMA‐β指数降低显著相关（P<0.05）。校正年龄、性别和体重指数后，JAZF1 rs864745，FTO rs8050136和 HHEX/IDE rs5015480的基因变异与估算肾小球滤过率下降显著相关（P<0.05）。WFS1 rs10010131，CDKN2A/B rs10811661，CDC123/CAMID rs12779790，JAZF1 rs864745，FTO rs80501360， CDKAL1 rs10946398和HHEX/IDE rs5015480 等的基因变异与主要的明尼苏达编码异常显著相关（P< 0.05）。 结论 WFS1，CDKN2A/B，KCNJ11，CDC123/CAMK1D，JAZF1，SLC30A8，FTO，CDKAL1和 HHEX/IDE等的基因变异与中国畲族人群的2型糖尿病显著相关。JAZF1，FTO，CDKAL1和 HHEX/IDE等的基因变异与糖尿病肾病相关。WFS1， CDKN2A/B，CDC123/CAMK1D，JAZF1，FTO，CDKAL1和 HHEX/IDE等的基因变异与心血管风险相关。