Association of FCRL3 Gene Polymorphisms with IgA Nephropathy in a Chinese Han Population
Association of FCRL3 Gene Polymorphisms with IgA Nephropathy in a Chinese Han Population
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FCRL3基因多态性与中国汉族人群IgA肾病的相关性
DOI：
10.1089/dna.2019.4900
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发表时间：
2019
影响因子：
3.1
通讯作者：
Li Ming
中科院分区：
文献类型：
--
作者：
Zhong Zhong;Feng Shaozhen;Shi Dianchun;Xu Ricong;Yin Peiran;Wang Meng;Mao Haiping;Huang Fengxian;Li Zhijian;Yu Xueqing;Li Ming
我们先前的全基因组关联研究发现，在中国汉族人群中，1q23.1上的FCRL3(Fc受体样3)基因座rs11264799可能与IgA肾病(IgAN)相关。本研究旨在探讨FCRL3基因变异与IgAN易感性、临床病理表型及预后的关系。对1750例IgA肾病患者和2500例健康对照进行了FCRL3单核苷酸多态分析。非条件Logistic回归模型用于估计优势比和95%可信区间(CI)，在PLINK软件中实现。采用荧光素酶分析法检测rs11264794基因表达调控的等位基因效应。经Bonferroni校正后，我们发现4个SNP(rs11264794、rs7865684、rs11264799和rs6691569)与IgAN易感性显著相关。基因/表型关联分析发现，两个SNPs(rs11264794和rs11264793)与疾病严重程度相关。调整混杂因素后，rs11264794与IgA肾病患者的肾脏预后独立相关(危险比 = 为0.64，95%CI = 为0.43-0.97，p= 0.033)。此外，rs11264794的保护等位基因A与FCRL3基因的高表达显著相关。此外，荧光素酶报告基因分析表明，rs11264794的次要等位基因显著降低了miR-183-5p.1与FCRL33‘-非翻译区的特异性结合。结果表明，FCRL3基因多态性与IgAN的发生发展有关，rs11264794-A等位基因对IgAN具有保护作用。
Our previous genome-wide association study has identified a suggestive association at rs11264799 withinFCRL3(Fc receptor-like 3) locus on 1q23.1 for IgA nephropathy (IgAN) in a Chinese Han population. This study aims to investigate the association ofFCRL3variants with the susceptibility, clinicopathological phenotypes and prognosis of IgAN. ElevenFCRL3single-nucleotide polymorphisms (SNPs) were selected and analyzed in this two-stage case/control study with a total of 1750 IgAN cases and 2500 healthy controls in a Chinese Han population. Unconditional logistic regression models were used to estimate odds ratios and 95% confidence intervals (CIs) as implemented in the PLINK software. Luciferase assays were applied to detect the allelic effect of rs11264794 on gene expression regulation. We found that four SNPs (rs11264794, rs7865684, rs11264799, and rs6691569) were significantly associated with IgAN susceptibility after Bonferroni correction in the combined samples. Genotype/phenotype association analysis observed that two SNPs (rs11264794 and rs11264793) were associated with less disease severity. After adjusting for confounders, rs11264794 was independently correlated with renal outcome in IgAN patients (hazard ratio = 0.64, 95% CI = 0.43–0.97,p= 0.033). In addition, the protective allele A of rs11264794 was significantly associated with higherFCRL3gene expression. Furthermore, luciferase reporter gene assays demonstrated that the minor allele of rs11264794 obviously reduced the specific binding between miR-183-5p.1 andFCRL33′-untranslated region. Our results indicate thatFCRL3gene polymorphisms are associated with the development and progression of IgAN, and the rs11264794-A allele showed a protective role for IgAN.