摘要
目的研究P-选择素基因变异与原发性IgA肾病的相关性。方法在用直接测序法广泛筛查P-选择素基因全部编码区、部分调控区和外显子-内含子连接区并发现16个单核苷酸多态性(SNP)的基础上,挑选9个中高频SNPs(频率>5％)。选上海瑞金医院肾科收治的汉族原发性IgA肾病患者210例及健康对照者103例,用PCR产物直接测序法进行基因分型,对IgA肾病进行病例-对照相关分析。结果(1)IgA肾病者AA基因型频率(78．1％)明显高于健康对照者(65．1％,P =0．0136),AG+GG基因型频率(21．9％)明显低于健康对照者(34．9％,P=0．0136);IgA肾病者等位基因A频率(88．6％)明显高于健康对照者(81．6％,P=0．0165),等位基因G频率(11．4％)明显低于健康对照者(18．4％,P=0．0165)。危险度相关分析,AG+GG基因型使IgA肾病发病危险性下降为52．2％(OR=0．522,95％CI为0．311～0．875)。(2)96例IgA肾病者外周血P-选择素水平为(26．8±9．1)μg／L,显著高于健康对照者[(19．6±4．5)μg／L,P<0．01],-825A／G多态性AA基因型者的P-选择素水平[(28．1±9．0)μg／L]显著高于AG+GG基因型[(23．4±8．5)μg／L,P<0．05]。结论P-选择素基因启动子区-825A／G与IgA肾病易感性及患者肾功能显著相关,揭示了P-选择素基因在IgA肾病中的致病作用。
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 genotypo 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-seleetin gene was significantly associated with IgA nephropathy suseeptlbility and patient＇ s renal function, thus suggesting the genetic effect of P-seleetin gene in the pathogenesis of IgA nephropathy.
出处
《中华内科杂志》
CAS
CSCD
北大核心
2006年第7期559-564,共6页
Chinese Journal of Internal Medicine
基金
上海市卫生局重大课题(2003ZD002)
上海市卫生局领先专业重点学科基金(05III001)
上海市重点学科基金(T0201)
上海第二医科大学自然科学基金资助项目(02XJ21018)
关键词
IGA肾病
易感基因
多态性
单核苷酸
P选择素
IgA nephropathy
Susceptibility gene
Polymorphism,single nucleotide
P-selectin
