C1GALT1基因单核苷酸多态性与IgAV易感性的相关性研究

Study on the Correlation between Single Nucleotide Polymorphisms of C1GALT1 Gene and Susceptibility to Immunoglobulin A Vasculitis (IgAV)

摘要: 目的：研究核心1β1,3半乳糖基转移酶(C1GALT1)基因4个单核苷酸多态性位点(rs13226913、rs7790522、rs1047763、rs5882115)与IgA血管炎(IgAV)及IgA血管炎肾炎(IgAVN)的相关性。方法：本项课题共选取IgA血管炎(IgAV)患病儿童156例设为病例组；依据患儿是否伴随肾脏损害情况，将IgAV患病儿童划分为紫癜性肾炎(IgAVN)组、非紫癜性肾炎(NIgAVN)组；按照患儿是否存在腹痛、关节痛表现，分成有腹痛症状组、无腹痛症状组，有关节疼痛症状组、无关节疼痛症状组；根据IgAVN患病儿童是否出现蛋白尿现象，将其分为伴蛋白尿组与无蛋白尿组。此外选取152例健康儿童作为正常参照组。采用iMLDR^TM多重SNP分型技术对C1GALT1基因的4个单核苷酸多态性位点(rs13226913、rs7790522、rs1047763、rs5882115)进行基因分型，分析各SNP与IgAV易感性及各临床表型之间的相关性。结果：C1GALT1基因中rs5882115中TC等位基因在蛋白尿组(44%)中的分布频率高于无蛋白尿组(13%)，差异具有统计学意义(P < 0.05)，C1GALT1基因上述4个位点的等位基因分布频次，在病例组与对照组之间的差异未达统计学显著水平(P > 0.05)；对上述四个单核苷酸多态性位点进行连锁不平衡及单倍型分析，发现其中rs5882115、rs7790522、rs1047763等位基因组成的TCGG单倍型在蛋白尿组分布频率大于无蛋白尿组，具有统计学意义(P < 0.05)。结论：rs5882115中TC等位基因可能是IgAVN儿童出现蛋白尿的易感等位基因，而与儿童IgAV易感性无相关性；IgAVN患儿在TCGG单倍型的遗传背景下出现蛋白尿的风险更高；未发现C1GALT1基因rs13226913、rs7790522、rs1047763位点单核苷酸多态性与IgAV易感性及其临床表现的相关性。

Abstract: Objective: This study aims to explore the potential relationship between four specific single nucleotide polymorphisms (SNPs) located at rs13226913, rs7790522, and two other SNPs (rs7843021 and rs1000130) and their impact on immunoglobulin A vasculitis (IgAV) as well as IgA vasculitis nephritis (IgAVN). Methods: A total of 156 children with IgAV were enrolled as the case group. Based on the presence or absence of renal injury, these children were divided into the purpura nephritis (IgAVN) group and the non-purpura nephritis (NIgAVN) group. They were further divided into abdominal pain group, non-abdominal pain group, joint pain group, and non-joint pain group according to the presence or absence of abdominal pain and joint pain symptoms. In addition, children with IgAVN were divided into the proteinuria group and the non-proteinuria group based on the presence or absence of proteinuria. Meanwhile, 152 healthy children were selected as the normal control group. The iMLDRTM multiplex SNP genotyping technology was used to genotype the four SNP loci (rs13226913, rs7790522, rs1047763, rs5882115) of the C1GALT1 gene, and the association between each SNP and the susceptibility to IgAV as well as various clinical phenotypes was analyzed. Results: The frequency of the TC allele at rs5882115 of the C1GALT1 gene was higher in the proteinuria group (44%) than in the non-proteinuria group (13%), with a statistically significant difference (P < 0.05). There was no statistically significant difference in the allele distribution frequency at these four loci of the C1GALT1 gene between the case group and the control group (P > 0.05). Linkage disequilibrium and haplotype analysis of the above four SNP loci showed that the frequency of the TCGG haplotype (composed of alleles of rs5882115, rs7790522, and rs1047763) in the proteinuria group was higher than that in the non-proteinuria group, with statistical significance (P < 0.05). Conclusion: The TC allele at rs5882115 may be a susceptible allele for proteinuria in children with IgAVN, but it is not associated with the susceptibility to IgAV in children. Children with IgAVN have a higher risk of developing proteinuria in the genetic background of the TCGG haplotype. No association was found between the SNPs at rs13226913, rs7790522, and rs1047763 loci of the C1GALT1 gene and the susceptibility to IgAV and its clinical manifestations.