Wang Zhao-hui, Chen Nan, Pan Xiao-xia, Ren Hong, Wang Wei-ming, Zhang Wen, Hao Cui-lan, Zhu Jie, Lu Ying, Han Bin
Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University School of Medical, Shanghai 200025, China.
Zhonghua Yi Xue Za Zhi. 2006 May 23;86(19):1337-41.
To investigate whether the single nucleotide polymorphisms (SNPs) in the gene of megsin, a novel serine protease inhibitor, account for the pathogenicity of IgA nephropathy (IgAN).
A comprehensive megsin gene survey, including the entire coding region, part of the regulatory region, and exon-intron connection region, was performed by PCR-direct sequencing on the DNA samples of peripheral blood from 12 randomly selected IgAN patients and 12 randomly selected healthy persons. Eight SNPs with moderate or high frequencies (with the frequency > 5%) selected from the 11 SNPs found were used as candidate SNPs. Then 210 IgAN patients proven by renal-biopsy, all of Chinese Han nationality, and 103 normal volunteers were recruited. The 8 candidate SNPs were genotyped by direct sequencing or PCR-RFLP and a case-control association study was carried out.
The SNP of 267G/A in 5'untranslated region within exon1 was significantly associated with IgAN. The frequency of AG/AA genotype of the IgA patients was 29.0%, significantly higher than that of the controls (16.5%, P < 0.05). The frequency of A allele of the IgA patients was 14.8%, significantly higher than that of the controls (8.7%, P < 0.05). The odds ratio of AG/AA genotype versus GG genotype was 2.07 with the 95% confidence interval of 1.15 - 3.74. The linkage disequilibrium between two SNPs existed commonly within one gene.
267G/A in megsin gene is associated with IgAN susceptibility. AG and AA genotypes are the risk factors of pathogenesis of IgAN.
研究新型丝氨酸蛋白酶抑制剂megsin基因中的单核苷酸多态性（SNP）是否与IgA肾病（IgAN）的致病性相关。
采用聚合酶链反应直接测序法，对随机选取的12例IgAN患者和12例健康人的外周血DNA样本进行全面的megsin基因检测，检测区域包括整个编码区、部分调控区以及外显子-内含子连接区。从检测到的11个SNP中选取8个中高频SNP（频率>5%）作为候选SNP。随后招募了210例经肾活检确诊的中国汉族IgAN患者和103名正常志愿者。采用直接测序法或聚合酶链反应-限制性片段长度多态性法对8个候选SNP进行基因分型，并开展病例对照关联研究。
外显子1内5'非翻译区的267G/A SNP与IgAN显著相关。IgA患者AG/AA基因型频率为29.0%，显著高于对照组（16.5%，P<0.05）。IgA患者A等位基因频率为14.8%，显著高于对照组（8.7%，P<0.05）。AG/AA基因型与GG基因型的比值比为2.07，95%置信区间为1.15 - 3.74。同一基因内两个SNP之间普遍存在连锁不平衡。
megsin基因中的267G/A与IgAN易感性相关。AG和AA基因型是IgAN发病机制的危险因素。
