title: FCGR2B and FCRLB gene polymorphisms associated with IgA nephropathy.
abstract: BACKGROUND
  IgA nephropathy (IgAN) is a complex syndrome characterized by deposition of IgA and IgA containing immune complexes (ICs) composed of IgG and complement C3 proteins in the mesangial area of glomeruli. The low-affinity receptors for the Fc region of IgG (FcγRs) are involved in autoantibody/immune complex-induced organ injury as well as ICs clearance. The aim of the study was to associate multiple polymorphisms within FCGR gene locus with IgAN in a large Chinese cohort.
  
  
  METHODS
  60 single nucleotide polymorphisms (SNPs) spanning a 400 kb range within FCGR gene locus were analyzed in 2100 DNA samples from patients with biopsy proven IgAN and healthy age- and sex-matched controls from the same population in Chinese.
  
  
  RESULTS
  Among the 60 SNPs investigated, 15 gene polymorphisms within FCGR gene locus (25%) were associated with susceptibility to IgAN. The most significantly associated SNPs within individual genes were FCGR2B rs12118043 (p = 8.74*10(-3), OR 0.76, 95% CI 0.62-0.93), and FCRLB rs4657093 (p = 2.28*10(-3), OR 0.77, 95% CI 0.65-0.91). Both conditional analysis and linkage disequilibrium analysis suggested they were independent signals associated with IgAN. Associations between FCGR2B rs12118043 and proteinuria (p = 3.65×10(-2)) as well as gross hematuria (p = 4.53×10(-2)), between FCRLB rs4657093 and levels of serum creatinine (p = 2.67×10(-2)) as well as eGFR (p = 5.41*10(-3)) were also observed. Electronic cis-expression quantative trait loci analysis supported their possible functional significance, with protective genotypes correlating lower gene expressions.
  
  
  CONCLUSIONS
  Our data from genetic associations and expression associations revealed potentially pathogenic roles of Fc receptor gene polymorphisms in IgAN.
authors.affiliation: Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, PR China.
authors.forename: Xu-jie
authors.initials: XJ
authors.lastname: Zhou
authors.forename: Fa-juan
authors.initials: FJ
authors.lastname: Cheng
authors.forename: Yuan-yuan
authors.initials: YY
authors.lastname: Qi
authors.forename: Yan-feng
authors.initials: YF
authors.lastname: Zhao
authors.forename: Ping
authors.initials: P
authors.lastname: Hou
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Ji-cheng
authors.initials: JC
authors.lastname: Lv
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D058851:GPI-Linked Proteins / Q000235:genetics; D018628:Gene Dosage / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics; D011961:Receptors, Fc / Q000235:genetics*; D017452:Receptors, IgG / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: C499173:FCGR2B protein, human; C428200:FCGR3B protein, human; C504209:FCRLB protein, human; D058851:GPI-Linked Proteins; D011961:Receptors, Fc; D017452:Receptors, IgG