Tien Kai-Jen, Hsiao Jeng-Yueh, Hsu Shih-Chieh, Liang Hui-Ting, Lin Shiu-Ru, Chen Hung-Chun, Hsieh Ming-Chia
Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Am J Nephrol. 2009;29(4):299-308. doi: 10.1159/000163592. Epub 2008 Oct 10.
We investigated the gender differences in the effect of ACE I/D and AGT M235T polymorphisms on the prognosis of diabetic nephropathy (DN).
A total of 525 type 2 diabetics were enrolled to participate in this prospective observational study. ACE and AGT gene polymorphisms were analyzed by polymerase chain reaction. The progression of DN was defined as a shift to a higher stage of DN or a doubling of the baseline serum creatinine level by the end of the study.
The baseline biophysical parameters show no gender differences in progression and non-progression of DN. The women who were ACE D allele carriers were found to be at an increased risk of DN progression compared to those with II genotypes (p = 0.024, OR 2.176). No such difference was seen in male patients (p = 0.619, OR 0.833). After adjusting for confounding factors (age, SBP, DBP, BMI, HbA1c, total cholesterol, TG, HDL-C, LDL-C, ACEI, and ARB) in our multiple regression analysis, these women were still found to be at increased risk of progressing to more severe DN (p = 0.008, OR 3.082) but not the men (p = 0.183, OR 0.586). Neither the AGT TT genotype nor the T allele were associated with the progression of DN in either sex after adjusting for confounding factors.
Our follow-up study suggests that female diabetic carriers of the ACE D allele might be at an increased risk of DN progression.
我们研究了血管紧张素转换酶（ACE）基因I/D多态性和血管紧张素原（AGT）基因M235T多态性对糖尿病肾病（DN）预后影响的性别差异。
共纳入525例2型糖尿病患者参与这项前瞻性观察性研究。采用聚合酶链反应分析ACE和AGT基因多态性。DN的进展定义为在研究结束时病情进展至更高分期或基线血清肌酐水平翻倍。
基线生物物理参数显示DN进展组和非进展组之间无性别差异。与II基因型女性相比，携带ACE D等位基因的女性发生DN进展的风险增加（p = 0.024，比值比[OR] 2.176）。男性患者中未观察到此类差异（p = 0.619，OR 0.833）。在我们的多元回归分析中，校正混杂因素（年龄、收缩压、舒张压、体重指数、糖化血红蛋白、总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、血管紧张素转换酶抑制剂和血管紧张素受体阻滞剂）后，仍发现这些女性进展为更严重DN的风险增加（p = 0.008，OR 3.082），而男性则不然（p = 0.183，OR 0.586）。校正混杂因素后，AGT TT基因型和T等位基因均与任何性别DN的进展无关。
我们的随访研究表明，携带ACE D等位基因的女性糖尿病患者发生DN进展的风险可能增加。
