School of Population Health, University of Queensland, Brisbane, Queensland, Australia.
Division of Preventative Medicine and Health Services Research, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
Diabetes Res Clin Pract. 2014 Aug;105(2):261-70. doi: 10.1016/j.diabres.2014.04.015. Epub 2014 May 5.
Polymorphisms of the ADIPOQ gene were associated with diabetic nephropathy (DN) in case-control studies predominantly among European populations. Gender may modify the ADIPOQ associated risk for DN. We investigated the association of 18 ADIPOQ polymorphisms with DN in a prospective Taiwanese cohort of type 2 diabetes (T2D) and explored whether gender plays a role in this genetic association.
Selected single nucleotide polymorphisms (SNPs) of ADIPOQ were genotyped in 566 T2D patients with normoalbuminuria at baseline. DN was defined based on urinary albumin-to-creatinine ratio (ACR). The Cox proportional hazard model was used to explore the association of individual SNP to DN events under different genetic models over a 6-year follow-up period. Analyses were further stratified by gender.
In male patients, the adjusted hazard ratios under the recessive models were 1.81 for rs2241766 TT (vs. GT+GG, 95% CI=1.10-2.96, p=0.019) and 1.89 for rs1063537 CC (vs. CT+TT, 95% CI=1.15-3.11, p=0.013). In the Kaplan-Meier survival curve, males carrying rs2241766 TT (vs. GT+GG, p=0.050) and rs1063537 CC (vs. CT+TT, p=0.037) recessive homozygotes also had a reduced nephropathy-free survival rate. SNPs rs2241767 and rs2082940, both in strong correlation with tag SNP rs1063537 (r(2)≥ 0.96), were also associated with DN progression in males. In females, ADIPOQ polymorphisms were not associated with the progression of DN.
ADIPOQ genetic polymorphisms rs2241766 (+45T>G), rs1063537, rs2241767 and rs2082940 were correlated with the progression of DN in Taiwanese male patients with T2D. The role of gender in this ADIPOQ genetic association needs to be further investigated in other populations.
ADIPOQ 基因的多态性与糖尿病肾病（DN）有关，这在主要以欧洲人群为研究对象的病例对照研究中已经得到证实。性别可能会改变 ADIPOQ 相关的 DN 风险。本研究旨在通过前瞻性的台湾 2 型糖尿病（T2D）队列研究，探讨 18 个 ADIPOQ 多态性与 DN 的相关性，并探讨性别是否在这种遗传相关性中起作用。
在基线时，对 566 名无白蛋白尿的 T2D 患者进行 ADIPOQ 选择的单核苷酸多态性（SNP）基因分型。DN 是根据尿白蛋白与肌酐比值（ACR）定义的。在 6 年的随访期间，采用 Cox 比例风险模型，在不同的遗传模型下，探讨个体 SNP 与 DN 事件的相关性。进一步按性别分层分析。
在男性患者中，在隐性模型下，rs2241766 TT（与 GT+GG 相比，95%CI=1.10-2.96，p=0.019）和 rs1063537 CC（与 CT+TT 相比，95%CI=1.15-3.11，p=0.013）的调整后的危险比分别为 1.81 和 1.89。在 Kaplan-Meier 生存曲线中，携带 rs2241766 TT（与 GT+GG 相比，p=0.050）和 rs1063537 CC（与 CT+TT 相比，p=0.037）隐性纯合子的男性，其肾病无进展生存率也降低。与标签 SNP rs1063537 密切相关的 SNPs rs2241767 和 rs2082940 也与男性的 DN 进展有关。在女性中，ADIPOQ 多态性与 DN 的进展无关。
ADIPOQ 基因多态性 rs2241766（+45T>G）、rs1063537、rs2241767 和 rs2082940 与台湾 T2D 男性患者的 DN 进展相关。性别在这种 ADIPOQ 遗传相关性中的作用需要在其他人群中进一步研究。
