Replication of genome-wide association signals of type 2 diabetes in Han Chinese in a prospective cohort
Replication of genome-wide association signals of type 2 diabetes in Han Chinese in a prospective cohort
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DOI：
10.1111/j.1365-2265.2011.04175.x
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发表时间：
2012-03-01
影响因子：
3.2
通讯作者：
Chuang, Lee-Ming
中科院分区：
文献类型：
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作者：
Chang, Yi-Cheng;Chiu, Yen-Feng;Chuang, Lee-Ming
背景最近一项针对中国汉族2型糖尿病的全基因组关联研究发现了几种新的遗传变异。我们研究了它们与定量测量的关系，以探索这些变异体影响葡萄糖稳态的机制。我们还研究了这些变异是否预测了一个大的前瞻性家庭为基础的中国coherent.Methods五个单核苷酸多态性（SNPs）附近的蛋白酪氨酸磷酸酶，受体类型，D（PTPRD），SRR，MAF/WWOX，和KCNQ 1基因分型1138例中国血统的受试者从斯坦福大学亚太高血压和胰岛素抵抗研究项目。MAF/WWOX基因附近的rs7192960 C等位基因与低稳态模型β细胞（HOMA-β）（P = 0 0 1）和口服葡萄糖耐量试验（OGTT）第二相胰岛素反应（P = 0 0 4）相关。KCNQ 1基因rs 2237897 C等位基因与空腹血糖升高（P = 0009）、HOMA β降低（P = 003）和OGTT第一时相胰岛素反应降低（P = 003）相关。在平均5.43年的随访期内，PTPRD基因中具有风险赋予rs 17584499 TT基因型的参与者比非携带者更有可能从非糖尿病进展为糖尿病（风险比：8.82，P = 4x 10（-5））。PTPRD基因中的T等位基因与胰岛素抵抗的稳态模型评估（HOMA-IR）随时间的增加（P = 0.04）。结论KCNQ 1和MAF/WWOX基因附近的遗传变异与胰岛素分泌减少有关。PTPRD基因变异似乎与中国汉族人糖尿病的进展有关，最有可能是通过增加胰岛素抵抗。
Background A recent genome-wide association study for type 2 diabetes in Han Chinese identified several novel genetic variants. We investigated their associations with quantitative measures to explore the mechanism by which these variants influence glucose homoeostasis. We also examined whether these variants predict progression to diabetes in a large prospective family based Chinese cohort.Methods Five single nucleotide polymorphisms (SNPs) near the protein tyrosine phosphatase, receptor type, D (PTPRD), SRR, MAF/WWOX, and KCNQ1 genes were genotyped in 1138 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance study.Results At baseline, the risk-conferring rs7192960 C allele near the MAF/WWOX genes was associated with lower homoeostasis model assessment of beta-cell (HOMA-beta) (P = 0 01) and secondphase insulin response in oral glucose tolerance test (OGTT) (P = 0 04). The risk-conferring rs2237897 C alleles in the KCNQ1 gene were associated with higher fasting glucose (P = 0 009), lower HOMA-beta (P = 0 03), and lower first-phase insulin response in OGTT (P = 0 03). Over an average follow-up period of 5.43 years, participants with the risk-conferring rs17584499 TT genotype in the PTPRD gene were more likely to progress from nondiabetes to diabetes than were noncarriers (hazard ratio: 8 82, P = 4 x 10(-5)). The risk-conferring T allele in the PTPRD gene was associated with greater increase in homoeostasis model assessment of insulin resistance (HOMA-IR) (P = 0 04) over time. PTPRD gene expression in human adipose tissues was negatively associated with fasting insulin levels and HOMA-IR.Conclusion Genetic variants near the KCNQ1 and MAF/WWOX genes are associated with reduced insulin secretion. The PTPRD genetic variant appears to be associated with progression to diabetes in Han Chinese, most likely through increased insulin resistance.