内皮型一氧化氮合酶基因对常染色体显性遗传性多囊肾病终末期肾病进展的影响。

Effects of endothelial nitric oxide synthase gene on end stage renal disease progression in autosomal dominant polycystic kidney disease.

作者信息

Xue Cheng, Zhou Chen-Chen, Sun Li-Jun, He Liang-Liang, Xu Cheng-Gang, Dai Bing, Mei Chang-Lin

机构信息

Department of Nephrology, 252 Hospital of the Chinese People's Liberation Army, Beijing, China; Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.

出版信息

Nephrology (Carlton). 2014 Oct;19(10):630-7. doi: 10.1111/nep.12310.

DOI:10.1111/nep.12310

PMID:24995932

Abstract

AIM

To investigate whether endothelial nitric oxide synthase (eNOS) gene associate with the progression of autosomal dominant polycystic kidney disease (ADPKD).

METHODS

Databases of EMBASE, Pubmed, ISI, Ovid Database, Cochrane library and China National Knowledge Infrastructure were all searched. Associated studies about eNOS polymorphisms and ADPKD were analyzed by meta-analysis.

RESULTS

A total of 11 studies with Glu298Asp and 4b/a polymorphisms were included. A allele of the 4b/a polymorphism increased the risk of end stage renal disease (ESRD) in ADPKD (odds ratio (OR) = 1.85, 95% confidence interval (CI) 1.17-2.94, P = 0.009). However, GG phenotype of Glu298Asp polymorphism neither decreased the ESRD risk (OR = 0.77, 95% CI 0.55-1.08, P = 0.13) nor affected the hypertension risk (OR = 1.04, 95% CI 0.66-1.66, P = 0.86). The GG phenotype carriers had later ESRD age compared with the T allele of Glu298Asp polymorphism (WMD = 2.39; 95% CI 1.32-3.46; P < 0.0001). Significant association was also found in Caucasians (WMD = 2.41; 95% CI 1.18-3.64; P = 0.0001). Subgroup analysis by gender indicated GG genotype carriers had older age of ESRD than T allele carriers in males (WMD = 4.51; 95% CI 3.95-5.08; P = 0.00001), but not in females.

CONCLUSIONS

GG genotype of the Glu298Asp variant slowed the ESRD progression in ADPKD, while a allele carriers of the 4b/a variant increased the risk of ESRD. Variants of eNOS gene might play different roles in the ESRD progression in ADPKD.

摘要

目的

研究内皮型一氧化氮合酶（eNOS）基因是否与常染色体显性多囊肾病（ADPKD）的进展相关。

方法

检索EMBASE、Pubmed、ISI、Ovid数据库、Cochrane图书馆及中国知网数据库。通过荟萃分析对eNOS基因多态性与ADPKD的相关研究进行分析。

结果

共纳入11项关于Glu298Asp和4b/a基因多态性的研究。4b/a基因多态性的A等位基因增加了ADPKD患者终末期肾病（ESRD）的风险（比值比（OR）=1.85，95%置信区间（CI）1.17 - 2.94，P = 0.009）。然而，Glu298Asp基因多态性的GG基因型既未降低ESRD风险（OR = 0.77，95% CI 0.55 - 1.08，P = 0.13），也未影响高血压风险（OR = 1.04，95% CI 0.66 - 1.66，P = 0.86）。与Glu298Asp基因多态性的T等位基因携带者相比，GG基因型携带者的ESRD发病年龄更晚（加权均数差（WMD）= 2.39；95% CI 1.32 - 3.46；P < 0.0001）。在白种人中也发现了显著相关性（WMD = 2.41；95% CI 1.18 - 3.64；P = 0.0001）。按性别进行的亚组分析表明，男性中GG基因型携带者的ESRD发病年龄比T等位基因携带者大（WMD = 4.51；95% CI 3.95 - 5.08；P = 0.00001），而女性中未发现此差异。