内皮型一氧化氮合酶基因多态性对常染色体显性遗传性多囊肾病和IgA肾病进展的影响。

Influence of the endothelial nitric oxide synthase polymorphism on the progression of autosomal dominant polycystic kidney disease and IgA nephropathy.

作者信息

Merta Miroslav, Reiterová Jana, Tesar Vladimír, Stekrová Jitka, Viklický Ondrej

机构信息

Department of Nephrology, Prague, Czech Republic.

出版信息

Ren Fail. 2002 Sep;24(5):585-93. doi: 10.1081/jdi-120013961.

DOI:10.1081/jdi-120013961

PMID:12380903

Abstract

BACKGROUND

The reason of variability of clinical course and progression to end-stage renal failure (ESRF) of two widespread chronic nephropathies--autosomal dominant polycystic kidney disease (ADPKD) and IgA nephropathy (IGAN) is not clear. The endothelial dysfunction is considered in the number of factors possibly influencing the prognosis of these nephropathies. Our study tried to verify the hypothesis that endothelial nitric oxide synthase (ecNOS) gene polymorphisms in intron 4 could have some relevance to the progression of ADPKD and/or IgA nephropathy.

METHODS

We examined 128 Czech patients with ADPKD (62 males, 66 females) and 93 patients with IGAN (51 males, 42 females). As a control group, we used 100 genetically unrelated healthy subjects (50 men, 50 women, mean age 51.2 +/- 8.2). The genomic DNA was amplified by polymerase chain reaction (PCR) and the products were separated on 1.5% agarose gel and visualized by ultraviolet transillumination. We compared homozygous subjects for ecNOSb allele with homozygous and heterozygous subjects for ecNOSa allele.

RESULTS

The frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes were 19% (19/100) and 81% (81/100) in the control group. The frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes in ADPKD patients were: 26.6% (8/30) and 73.4% (22/30) in ADPKD patients with normal renal function, 30% (9/30) and 70% (21/30) in ADPKD with ESRF, 35.2% (18/51) and 64.8% (33/51) in young ADPKD patients, 60% (12/20) and 40% (8/20) in ADPKD patients with ESRF later than in 62 years. In IGAN, the frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes were 24% (12/50) and 76% (38/50) in IgA with normal renal function and 20.9% (9/43) and 79.1% (38/43) in IgA with ESRF.

CONCLUSION

Both in ADPKD and IGAN groups, there was no significant difference in the frequencies of ecNOS genotypes between patients with normal renal function and age matched patients with ESRF and between patients with normal renal function and control group. The frequency of ecNOSa allele was significantly higher in a number limited group ADPKD patients with ESRF later than in 62 years (Chi-square test p < 0.05). This higher frequency of a allele among ADPKD patients with later onset of ESRF could suggest the trend of positive influence of a allele in ADPKD patients.

摘要

背景

两种常见的慢性肾病——常染色体显性遗传性多囊肾病（ADPKD）和IgA肾病（IGAN）的临床病程变异性及进展至终末期肾衰竭（ESRF）的原因尚不清楚。内皮功能障碍被认为是可能影响这些肾病预后的多种因素之一。我们的研究试图验证这样一个假设，即内含子4中的内皮型一氧化氮合酶（ecNOS）基因多态性可能与ADPKD和/或IgA肾病的进展有关。

方法

我们检查了128例捷克ADPKD患者（男性62例，女性66例）和93例IGAN患者（男性51例，女性42例）。作为对照组，我们使用了100名无亲缘关系的健康受试者（男性50例，女性50例，平均年龄51.2±8.2岁）。基因组DNA通过聚合酶链反应（PCR）进行扩增，产物在1.5%的琼脂糖凝胶上进行分离，并用紫外透射仪进行观察。我们将ecNOSb等位基因的纯合子受试者与ecNOSa等位基因的纯合子和杂合子受试者进行了比较。

结果

对照组中ecNOSa/b + a/a和ecNOSb/b基因型的频率分别为19%（19/100）和81%（81/100）。ADPKD患者中ecNOSa/b + a/a和ecNOSb/b基因型的频率分别为：肾功能正常的ADPKD患者中为26.6%（8/30）和73.4%（22/30），发生ESRF的ADPKD患者中为30%（9/30）和70%（21/30），年轻ADPKD患者中为35.2%（18/51）和64.8%（33/51），62岁以后发生ESRF的ADPKD患者中为60%（12/20）和40%（8/20）。在IGAN中，肾功能正常的IgA患者中ecNOSa/b + a/a和ecNOSb/b基因型的频率分别为24%（12/50）和76%（38/50），发生ESRF的IgA患者中为20.9%（9/43）和79.1%（38/43）。

结论

在ADPKD和IGAN组中，肾功能正常的患者与年龄匹配的发生ESRF的患者之间，以及肾功能正常的患者与对照组之间，ecNOS基因型的频率均无显著差异。在62岁以后发生ESRF的少数ADPKD患者中，ecNOSa等位基因的频率显著高于其他患者（卡方检验p < 0.05）。在发病较晚的ADPKD患者中，a等位基因的较高频率可能提示该等位基因对ADPKD患者有积极影响的趋势。