原发性IgA肾病中G蛋白β3亚基C825T多态性

G protein beta3 subunit C825T polymorphism in primary IgA nephropathy.

作者信息

Thibaudin Lise, Berthoux Patricia, Thibaudin Damien, Mariat Christophe, Berthoux François

机构信息

Department of Nephrology, Dialysis and Renal Transplantation, University North Hospital, Saint Etienne, France.

出版信息

Kidney Int. 2004 Jul;66(1):322-8. doi: 10.1111/j.1523-1755.2004.00734.x.

DOI:10.1111/j.1523-1755.2004.00734.x

PMID:15200440

Abstract

BACKGROUND

The T allele of the G protein beta3 subunit (GNB3) C825T polymorphism has been associated with increased signal transduction, increased activity of the kidney Na+/H+ exchanger, and also with late-onset essential hypertension. Hypertension is a strong independent risk factor for progression in IgA nephropathy (IgAN).

METHODS

We have studied this polymorphism in a regularly followed cohort of 299 biopsy-proven incident cases of IgAN, collected from 1989 to 1999 [208 males (70%)] and compared the genotypes and alleles distributions to 303 local Caucasian controls matched for the male predominance (214 males). The technique used was a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with BseDI as restriction enzyme and specific primers, followed by gel electrophoresis.

RESULTS

The TT, CT, and CC genotype frequencies were 13.7%, 45.8%, and 40.5% in IgAN, respectively, versus 7.6%, 47.2%, and 45.2% in controls, respectively (chi(2)= 6.16; P= 0.05). The excess of TT patients versus non-TT was significant in IgAN versus controls (chi(2)= 5.94; P= 0.015). The T allele frequency was 0.366 in IgAN versus 0.312 in controls (chi(2)= 3.97; P= 0.05). This data indicated that this polymorphism had a significant but mild influence on the occurrence/initiation of IgAN (RR = 1.81; 95% CI 1.07-3.07). In contrast, we could not demonstrate any significant and sustained difference in the clinical presentation and evolution of the homozygous TT patients compared to non-TT patients (CC + CT) despite a mean and median follow-up about 10 years. The progression to arterial hypertension or to chronic renal failure or to end-stage renal failure (ESRF) was not significantly different. In addition, multivariate Cox regression analysis excluded a significant independent role of C825T polymorphism on progression.

CONCLUSION

The C825T GNB3 polymorphism had a mild influence on occurrence/initiation of IgAN, but played no significant role in the progression of the disease.

摘要

背景

G蛋白β3亚基（GNB3）C825T多态性的T等位基因与信号转导增强、肾钠/氢交换体活性增加以及迟发性原发性高血压有关。高血压是IgA肾病（IgAN）进展的一个强大独立危险因素。

方法

我们在一个定期随访的队列中研究了这种多态性，该队列包括1989年至1999年收集的299例经活检证实的IgAN新发病例[208例男性（70%）]，并将基因型和等位基因分布与303名当地白种人对照进行比较，这些对照在男性占优势方面相匹配（214例男性）。所采用的技术是聚合酶链反应-限制性片段长度多态性（PCR-RFLP），以BseDI作为限制性内切酶和特异性引物，随后进行凝胶电泳。

结果

IgAN中TT、CT和CC基因型频率分别为13.7%、45.8%和40.5%，而对照组分别为7.6%、47.2%和45.2%（χ² = 6.16；P = 0.05）。IgAN患者中TT患者相对于非TT患者的过量在与对照组比较时具有显著性（χ² = 5.94；P = 0.015）。IgAN中T等位基因频率为0.366，而对照组为0.312（χ² = 3.97；P = 0.05）。该数据表明这种多态性对IgAN的发生/起始有显著但轻微的影响（RR = 1.81；95%CI 1.07 - 3.07）。相比之下，尽管平均和中位随访时间约为10年，但我们未能证明纯合子TT患者与非TT患者（CC + CT）在临床表现和病程方面有任何显著且持续的差异。进展为动脉高血压、慢性肾衰竭或终末期肾衰竭（ESRF）并无显著差异。此外，多变量Cox回归分析排除了C825T多态性在疾病进展中的显著独立作用。