The effects of both single-locus and multi-locus interaction on the clinical manifestations of IgA nephropathy in Southern Han Chinese.
The effects of both single-locus and multi-locus interaction on the clinical manifestations of IgA nephropathy in Southern Han Chinese.
复制标题
单基因座和多基因座相互作用对南方汉族 IgA 肾病临床表现的影响
DOI：
10.1093/ndt/gft468
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发表时间：
2014-03
期刊：
影响因子：
--
通讯作者：
Li M
中科院分区：
文献类型：
--
作者：
Sun Y;Fu Y;Yu X;Li M
背景
免疫球蛋白A肾病（IgAN）是全球最常见的肾小球肾炎类型之一。它被认为是一种复杂的疾病，遗传和环境因素都有影响。我们的前期研究表明C1 GALT 1 - 330 G/T和IL 5 RA 31 + 197 A/G在中国南方汉族人IgAN的易感性中存在潜在的相互作用。然而，这些基因多态性和IgAN的临床表现的相互作用还没有调查。
目的
本研究旨在探讨IgAN患者的遗传变异是否影响临床表现，并评估IgAN的基因型和表型之间的关系。
方法
本研究共筛选出24个候选基因中的31个SNPs，这些SNPs参与了IgAN发生、发展的相关通路。共调查了480例具有完整临床资料的IgAN患者。数据分析采用逻辑回归和多因素降维（MDR）。通过单位点和多位点互作模型与临床资料的相关性研究基因型-表型关联。
结果
G等位基因的ADD 1G 460 W-显性模式与IgAN患者的高血压显著相关（P = 0.001，Pc = 0.031，OR = 1.37）。TGF-β1- 509 T/C显性模式与IgAN患者蛋白尿（≥ 1.0g/d）显著相关（P = 0.001，Pc = 0.031，OR = 1.49）。多个SNPs的MDR分析显示，P-selectin-2441 A/G和CD 14 - 159 C/T在IgAN患者肉眼血尿中具有联合作用，而TGF-β1 509 T/C、P-selectin-2441 A/G和MCP-1 2518 A/G在IgAN患者新月体形成中具有联合作用。
结论
这些基因的单位点和多位点相互作用的影响可能会影响IgAN的临床表现。可能需要进一步的功能研究来确认这些遗传多态性的预后意义。
BACKGROUND
Immunoglobulin A nephropathy (IgAN) is one of the most common types of glomerulonephritis throughout the world. It is considered to be a complex disease, to which both genetic and environmental factors contribute. Our previous study has shown a potential interaction of C1GALT1-330G/T and IL5RA31 + 197A/G on the susceptibility of IgAN in Southern Han Chinese. However, the interaction of these gene polymorphisms and the clinical manifestation for IgAN has not been investigated.
OBJECTIVE
This study aims to investigate whether genetic variants influence the clinical manifestation for IgAN patients and to assess the relationship between the genotype and phenotype of IgAN.
METHODS
Thirty-one SNPs in 24 candidate genes were selected in this study, which were involved in the pathways implicated in the development or progression of IgAN. A total of 480 IgAN patients with integrated clinical data were investigated. Data were analyzed using logistic regression and multifactor dimensionality reduction (MDR). The genotype-phenotype association was studied by correlations of single-locus and multi-locus interaction models with the clinical data.
RESULTS
The ADD1 G460W-dominant model for the G allele was significantly associated with hypertension of IgAN patients (P = 0.001, Pc = 0.031 and OR = 1.37). The TGF-β1-509T/C-dominant model for the C allele was significantly associated with proteinuria (≥1.0 g/d) of IgAN patients (P = 0.001, Pc = 0.031 and OR = 1.49). The MDR analysis of multiple SNPs revealed that P-selectin-2441A/G and CD14-159C/T had combined effects on macroscopic hematuria, whereas TGF-β1 509T/C, P-selectin-2441A/G and MCP-1 2518A/G had combined effects on the formation of crescents in IgAN patients.
CONCLUSION
The effects of both single-locus and multi-locus interaction of these genes may influence the clinical manifestations of IgAN. Further functional studies may be required to confirm the prognostic significance of these genetic polymorphisms.
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