Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
J Hum Genet. 2013 Jan;58(1):40-6. doi: 10.1038/jhg.2012.133. Epub 2012 Nov 29.
IgA nephropathy is one of the most common glomerulonephritis throughout the world, which is thought to be the multifactorial complex diseases, with genetic and environmental factors contributing to this disease. The failure of replicating the single genes in previous association studies may be of that the gene-gene interaction might have more influence on the susceptibility of the complex diseases. In all, 31 single-nucleotide polymorphisms (SNPs) in 24 candidate genes (which were involved in the pathways implicated in the development or progression of IgAN) were selected to conduct a large case-control association study in 527 IgAN patients and 543 healthy controls. Traditional linear logistic regression analyses were used to detect single-locus associations in dominant, recessive and additive genetic models. Bonferroni correction was used to adjust the P-values for multiple testing. The gene-gene interaction effects of multiple SNPs were detected by multifactor-dimensionality reduction (MDR) method. After Bonferroni correction, no significant single-locus associations was observed between IgAN patients and controls (Pc>0.05). The MDR analysis showed a potential interaction of C1GALT1-330G/T (rs1008898) and IL5RA31+197A/G (rs340833) on the susceptibility of IgAN (P<0.001). Gene-gene interaction may have some influence on the susceptibility to IgA nephropathy. This finding proposed a potential gene-gene interactive model for future studies.
IgA 肾病是全世界最常见的肾小球肾炎之一，被认为是一种多因素复杂疾病，遗传和环境因素都可能导致这种疾病。之前的关联研究中复制单个基因的失败可能是由于基因-基因相互作用可能对复杂疾病的易感性有更大的影响。总之，在 24 个候选基因（涉及 IgAN 发展或进展的途径）中选择了 31 个单核苷酸多态性（SNP），对 527 例 IgAN 患者和 543 例健康对照进行了大型病例对照关联研究。传统的线性逻辑回归分析用于检测显性、隐性和加性遗传模型中的单基因座关联。Bonferroni 校正用于调整多重检验的 P 值。多因素降维（MDR）方法用于检测多个 SNP 的基因-基因相互作用效应。经 Bonferroni 校正后，IgAN 患者与对照组之间未观察到显著的单基因座关联（Pc>0.05）。MDR 分析显示 C1GALT1-330G/T（rs1008898）和 IL5RA31+197A/G（rs340833）之间存在潜在的相互作用，与 IgAN 的易感性有关（P<0.001）。基因-基因相互作用可能对 IgA 肾病的易感性有一定影响。这一发现为进一步研究提出了一个潜在的基因-基因相互作用模型。
