肾素-血管紧张素系统多态性与狼疮性肾炎更严重组织学类型之间的关联。

Association between polymorphisms of the renin-angiotensin system and more severe histological forms of lupus nephritis.

作者信息

Sprovieri S R S, Sens Y A, Martini Filho D

机构信息

Department of Medicine, Santa Casa de São Paulo Faculty of Medical Sciences, São Paulo, Brazil.

出版信息

Clin Nephrol. 2005 Jul;64(1):20-7. doi: 10.5414/cnp64020.

DOI:10.5414/cnp64020

PMID:16047641

Abstract

AIMS

The pathogenesis of lupus nephritis (LN) has not been fully understood. The renin-angiotensin system (RAS) is implicated in various immunological and non-immunological phenomena, and the polymorphism of the RAS genes has been associated with cardiovascular and renal disease onset and outcome. Therefore, we evaluated the possible association between the polymorphism of the renin-angiotensin system genes and the development of the different types of histological lesions of lupus nephritis in Brazilian patients.

METHODS

72 LN patients and 65 healthy subjects (sex-and ethnic-matched) were enrolled and compared in this study. Following the extraction of genomic DNA from the leukocytes of the peripheral blood, the genotypes of the angiotensin converting enzyme (ACE I/D), of the angiotensinogen (AGT M235T) and of the angiotensin II type 1 receptor (AGTR1 A1166C) were determined by the polymerase chain reaction. The renal lesions of the patients with LN were classified by the histological findings according to the WHO criteria. In addition, the activity and chronicity indices were used to assess the severity of renal involvement.

RESULTS

Among the 72 patients with LN, there were 17 class II, 8 class III, 40 class IV and 7 class V, according to the WHO criteria. Individuals with the III and IV classes of LN (WHO) showed a significantly increased DD genotype frequency of ACE I/D genes when compared to the control group (48% vs. 27.7%, chi2 = 4.885, df = 1, p = 0.0442). No difference was found in the distribution of the AGT M235T and AGTR1 A1166C genotype frequencies among the LN of the different histological classes (WHO) and healthy controls. There was no association between genetic polymorphism of ACE, AGT M235T and AGTR1 A1166C and susceptibility to lupus nephritis, nor histological activity and chronicity indices in renal biopsy among the patients studied.

CONCLUSIONS

This study suggests that the DD genotype of the ACE may be associated with the development of the more severe histological forms of lupus nephritis.

摘要

目的

狼疮性肾炎（LN）的发病机制尚未完全明确。肾素 - 血管紧张素系统（RAS）与多种免疫和非免疫现象相关，且RAS基因多态性与心血管及肾脏疾病的发病和转归有关。因此，我们评估了巴西患者中肾素 - 血管紧张素系统基因多态性与狼疮性肾炎不同类型组织学病变发展之间的可能关联。

方法

本研究纳入了72例LN患者和65名健康受试者（性别和种族匹配）并进行比较。从外周血白细胞中提取基因组DNA后，通过聚合酶链反应确定血管紧张素转换酶（ACE I/D）、血管紧张素原（AGT M235T）和血管紧张素II 1型受体（AGTR1 A1166C）的基因型。LN患者的肾脏病变根据WHO标准的组织学检查结果进行分类。此外，使用活动指数和慢性指数评估肾脏受累的严重程度。

结果

根据WHO标准，72例LN患者中，有17例为II级，8例为III级，40例为IV级，7例为V级。与对照组相比，LN的III级和IV级患者（WHO标准）的ACE I/D基因DD基因型频率显著增加（48%对27.7%，χ2 = 4.885，自由度 = 1，p = 0.0442）。在不同组织学类型（WHO标准）的LN患者和健康对照中，AGT M235T和AGTR1 A1166C基因型频率分布未发现差异。在研究的患者中，ACE、AGT M235T和AGTR1 A1166C的基因多态性与狼疮性肾炎易感性、肾活检中的组织学活动指数和慢性指数均无关联。