The effects of both single-locus and multi-locus interaction on the clinical manifestations of IgA nephropathy in Southern Han Chinese.

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-ß1-509T/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-ß1 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.