title: The effects of both single-locus and multi-locus interaction on the clinical manifestations of IgA nephropathy in Southern Han Chinese.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.forename: Yonggui
authors.initials: Y
authors.lastname: Fu
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yu
authors.forename: Ming
authors.initials: M
authors.lastname: Li
mesh_terms: D000328:Adult; D018932:Chemokine CCL2 / Q000235:genetics*; D002681:China; D018450:Disease Progression; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006801:Humans; D008297:Male; D058011:Multifactor Dimensionality Reduction; D019007:P-Selectin / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D055815:Young Adult
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D019007:P-Selectin; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1
keywords: IgA nephropathy; gene–gene interaction; genotype–phenotype correlation; multifactor dimensionality reduction