妊娠糖尿病患者中内皮型一氧化氮合酶基因G894T多态性及血清一氧化氮浓度与微量白蛋白尿的关系
The association of endothelial nitric oxide synthase gene G894T polymorphism and serum nitric oxide concentration with microalbuminuria in patients with gestational diabetes.
作者信息
Atay Ahmet Engin, Akbas Halit, Tumer Cemil, Sakar Mehmet Nafi, Esen Bennur, Incebiyik Adnan, Simsek Selda, Sit Dede
机构信息
Department of Internal Medicine, Bagcılar Education and Research Hospital, Istanbul, Department of Medical Biology, Medical School of Harran University, Sanlıurfa, Department of Physiology, Medical School of Mustafa Kemal University, Hatay, Department of Obstetrics and Gynecology, Suleymaniye Education and Research Hospital, Istanbul, Department of Obstetrics and Gynecology, Medical Faculty of Harran University, Sanlıurfa, and Department of Medical Biology and Genetics, Medical Faculty of Dicle University, Diyarbakir, Turkey.
出版信息
Clin Nephrol. 2014 Feb;81(2):105-11. doi: 10.5414/cn108138.
AIM
Gestational diabetes mellitus (GDM) is a glucose intolerant condition that affects 14% of all pregnancies. Diabetes mellitus (DM) occurs in 30 - 70% of patients with GDM after delivery. DM and GDM are associated with structural and functional deterioration of the renovascular system. Our aim is to investigate the association Glu- 298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene with serum nitric oxide levels and microalbuminuria in patients with GDM and healthy pregnancies.
MATERIAL AND METHODS
Serum nitric oxide (NO) levels, urinary excretion of albumin and Glu298Asp polymorphism of the eNOS gene were analyzed in 68 patients with GDM and 73 healthy controls. High performance liquid chromatography (HPLC-Griess) method was used to analyze serum NO levels. Microalbuminuria was evaluated by rate nephelometry method. The Glu298Asp polymorphism of the eNOS gene was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).
RESULTS
Nitric oxide, glucose, creatinine, and microalbuminuria were significantly different between the patients and the control subjects (p = 0.001, p = 0.001, p = 0.002, and p = 0.005, respectively). There was a significant difference between groups in terms of the ratio of GG/GT+TT of eNOS gene Glu- 298Asp (p = 0.02). The patients with GT+TT genotype had significantly higher microalbuminuria levels and lower NO concentrations (22.16 vs. 9.51, p = 0.005, and 10.56 vs. 12.73, p = 0.021, respectively). The presence of T allele of eNOS gene is an independent predictor of microalbuminuria (OR: 2.346, 95% confidence interval: 1.247 - 5.238, p = 0.02) as well as serum glucose and NO concentration.
CONCLUSION
The G894T polymorphism of eNOS gene and decreased NO concentration seem to be independent predictors of increased urinary excretion of albumin in patients with GDM. Determining the frequency of eNOS gene G894T polymorphism may help to identify pregnancies at increased risk of microalbuminuria.
目的
妊娠期糖尿病（GDM）是一种影响14%的妊娠女性的糖耐量异常病症。产后30% - 70%的GDM患者会发生糖尿病（DM）。DM和GDM与肾血管系统的结构和功能恶化相关。我们的目的是研究内皮型一氧化氮合酶（eNOS）基因Glu-298Asp多态性与GDM患者及正常妊娠女性血清一氧化氮水平和微量白蛋白尿之间的关联。
材料与方法
分析68例GDM患者和73例健康对照者的血清一氧化氮（NO）水平、尿白蛋白排泄量及eNOS基因的Glu298Asp多态性。采用高效液相色谱法（HPLC - Griess）分析血清NO水平。通过速率散射比浊法评估微量白蛋白尿。采用聚合酶链反应和限制性片段长度多态性（PCR - RFLP）方法测定eNOS基因的Glu298Asp多态性。
结果
患者与对照者之间的一氧化氮、血糖、肌酐和微量白蛋白尿有显著差异（分别为p = 0.001、p = 0.001、p = 0.002和p = 0.005）。eNOS基因Glu-298Asp的GG/GT + TT比值在两组之间存在显著差异（p = 0.02）。GT + TT基因型患者的微量白蛋白尿水平显著更高，NO浓度更低（分别为22.16对9.51，p = 0.005；10.56对12.73，p = 0.021）。eNOS基因T等位基因的存在是微量白蛋白尿以及血清葡萄糖和NO浓度的独立预测指标（比值比：2.346，95%置信区间：1.247 - 5.238，p = 0.02）。
结论
eNOS基因的G894T多态性和NO浓度降低似乎是GDM患者尿白蛋白排泄增加的独立预测指标。确定eNOS基因G894T多态性的频率可能有助于识别微量白蛋白尿风险增加的妊娠。
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