Polymorphism of angiotensin converting enzyme, angiotensinogen, and angiotensin II type 1 receptor genes and end-stage renal failure in IgA nephropathy: IGARAS - A study of 274 men
Polymorphism of angiotensin converting enzyme, angiotensinogen, and angiotensin II type 1 receptor genes and end-stage renal failure in IgA nephropathy: IGARAS - A study of 274 men
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DOI：
10.1681/asn.v11112062
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发表时间：
2000-11-01
影响因子：
13.6
通讯作者：
Kessler, M
中科院分区：
文献类型：
--
作者：
Frimat, L;Philippe, C;Kessler, M
肾素-血管紧张素系统(RAS)基因多态性对IgA肾病(IgAN)预后的影响仍存在争议。为探讨RAS基因多态与终末期肾功能衰竭(ESRF)的关系，对IgAN患者的肾脏预后进行了纵向研究。根据肾活检时测得的血肌酐(S-cr)和24小时蛋白尿(24-P)进行分类，以评估终末期肾病患者发生终末期肾功能衰竭的风险：阶段1(S-cr小于或等于150mmoL/L和24-P；1g)，阶段2(S-cr和24-P；1g或S-cr 150mU/gr和24-P>1g)，阶段3(S-cr和gt；150MmoL/L和24-P大于或等于1g)。检测274例高加索男性IgAN患者血管紧张素转换酶基因缺失/插入多态(D/I)、血管紧张素原基因M235T多态(T/M)和血管紧张素II1型受体基因A1166C多态(C/A)，其中第1、2、3期分别为86、112、76例。肾活检后平均随访6+/-5年。肾活检后1、2、3期分别有7例(8.1%)、39例(34.8%)和39例(64.4%)发生终末期肾功能衰竭(P<；0.0001)、11.7+/-4、5.3+/-4和2+/-2年(P<；0.001)。三种基因型在三个时期的分布基本一致。按临床分期和基因分型，ID+DD为72%，2+3期为84.6%(P=0.02；kappa=0.14)；MT+TT为66.2%，3期为78.9%(P=0.04；kappa=0.09)；AA+AC：89.9%，3期为97.4%(P=0.04；kappa=-0.1)。然而，使用COX比例风险模型，发现这三种基因对肾脏存活率都没有预测价值。与S-cr和24-P相比，DD、TT和AA型不太可能作为预测IgAN终末期肾功能衰竭的有用指标。
The impact of renin-angiotensin system (RAS) gene polymorphism on the prognosis of IgA nephropathy (IgAN) is still debated. A longitudinal study of renal prognosis in patients with IgAN was conducted to search retrospectively for a genotype-phenotype association between RAS polymorphisms and end-stage renal failure (ESRF). A classification based on serum creatinine (S-cr) and 24-h proteinuria (24-P) measured at the time of renal biopsy was used to estimate the risk of ESRF in IgAN: stage 1 (S-cr less than or equal to 150 mu mol/L and 24-P < 1 g), stage 2 (S-cr > 150 mu mol/L and 24-P < 1 g or S-cr 150 mu mol/L and 24-P greater than or equal to 1 g), stage 3 (S-cr > 150 mu mol/L and 24-P greater than or equal to 1 g). Deletion/insertion polymorphism (D/I) of the angiotensin I converting enzyme gene, M235T polymorphism (T/M) of the angiotensinogen gene and A1166C polymorphism (C/A) of the angiotensin II type 1 receptor gene were determined in 274 Caucasian men with biopsy-proven IgAN (n = 86, 112, and 76 in stages 1, 2, and 3, respectively). Mean global follow-up was 6 +/- 5 yr after renal biopsy. For stages 1, 2, and 3, ESRF developed in 7 (8.1%), 39 (34.8%), and 39 (64.4%) cases (P < 0.0001), 11.7 +/- 4, 5.3 +/- 4, and 2 +/- 2 yr, respectively, after renal biopsy (P < 0.001). The distributions of the three genotypes into the three stages were similar. Different distributions were observed when patients were grouped by stage and genotype: ID + DD: 72% in stage 1 versus 84.6% in stages 2 + 3 (P = 0.02; kappa = 0.14); MT + TT: 66.2% in stages 1 + 2 versus 78.9% in stage 3 (P = 0.04; kappa = 0.09); and AA + AC: 89.9% in stages 1 + 2 versus 97.4% in stage 3 (P = 0.04; kappa = -0.1). However, with the use of the Cox proportional hazard model, none of the three genotypes was found to have predictive value fur renal survival. Compared with S-cr and 24-P, genotypes DD, TT, and AA are unlikely to serve as clinically useful predictors of ESRF in IgAN.