[P-选择素基因单核苷酸多态性与IgA肾病的关联]

[The association of single nucleotide P-selectin gene polymorphism with IgA nephropathy].

作者信息

Wang Zhao-hui, Wang Wei-ming, Zhou Tong, Chen Xiao-nong, Pan Xiao-xia, Zhu Jie, Lu Ying, Han Bin, Chen Nan

机构信息

Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University, Shanghai 200025, China.

出版信息

Zhonghua Nei Ke Za Zhi. 2006 Jul;45(7):559-64.

PMID:17074110

Abstract

OBJECTIVE

IgA nephropathy is one of the most common form of primary glomerulonephritis throughout the world and a main renal disease which causes renal failure. P-selectin plays an important role in the pathogenesis and development of IgA nephropathy. The purpose of this study is to find a possible relationship between P-selectin gene polymorphism and IgA nephropathy.

METHODS

In this study, a comprehensive P-selectin gene survey, including entire coding region, part of regulatory region and exon-intron connection region, was performed with PCR-direct sequencing and 16 single nucleotide polymorphism (SNPs) were detected. Then 210 renal-biopsy proven sporadic IgA nephropathy cases of Chinese Han nationality and 103 normal volunteers were recruited. 9 candidate SNPs (frequency > 5%) in P-selectin gene of both the case and control groups were genotyped with direct sequencing and a case-control association study was carried out.

RESULTS

It was revealed that the SNP of -825A/G in promoter region of P-selectin gene was significantly associated with IgA nephropathy. Both the frequency of AG/GG genotype (21.9% vs 34.9%, P < 0.05) and G allele (11.4% vs 18.4%, P < 0.05) were less in the IgA nephropathy cases than in the healthy controls. Those carrying the low frequency G allele (AG/GG genotype) had a protective effect on the morbidity of IgA nephropathy and the odds ratio for the IgA nephropathy patients versus controls was 0.522 with AG/GG genotype versus AA genotype. Within the IgA nephropathy group, patients with AA genotype tended to present higher level of serum creatinine and soluble P-selectin than those carrying at least one G allele (AG/GG genotype) (P < 0.05).

CONCLUSION

The SNP of -825A/G in the promoter region of P-selectin gene was significantly associated with IgA nephropathy susceptibility and patient's renal function, thus suggesting the genetic effect of P-selectin gene in the pathogenesis of IgA nephropathy.

摘要

目的

IgA肾病是全球最常见的原发性肾小球肾炎类型之一，也是导致肾衰竭的主要肾脏疾病。P选择素在IgA肾病的发病机制和发展过程中起重要作用。本研究旨在探寻P选择素基因多态性与IgA肾病之间可能存在的关联。

方法

本研究采用PCR直接测序法对P选择素基因进行全面检测，涵盖整个编码区、部分调控区及外显子 - 内含子连接区，共检测到16个单核苷酸多态性（SNP）。随后招募了210例经肾活检确诊的中国汉族散发性IgA肾病患者及103名正常志愿者。采用直接测序法对病例组和对照组P选择素基因中的9个候选SNP（频率>5%）进行基因分型，并开展病例对照关联研究。

结果

研究发现，P选择素基因启动子区域 -825A/G的SNP与IgA肾病显著相关。IgA肾病患者中AG/GG基因型频率（21.9%对34.9%，P<0.05）和G等位基因频率（11.4%对18.4%，P<0.05）均低于健康对照组。携带低频G等位基因（AG/GG基因型）对IgA肾病发病具有保护作用，IgA肾病患者与对照组相比，AG/GG基因型与AA基因型的比值比为0.522。在IgA肾病组内，AA基因型患者的血清肌酐和可溶性P选择素水平往往高于携带至少一个G等位基因（AG/GG基因型）的患者（P<0.05）。