title: Variation in IGHMBP2 is not associated with IgA nephropathy in independent studies of UK Caucasian and Chinese Han patients.
abstract: BACKGROUND
  IgA nephropathy is a major cause of end-stage renal disease worldwide. Its aetiology is poorly understood but there is good evidence for a major genetic component, although to date, no gene has been conclusively identified. We describe a new UK multicentre DNA collection assembled to investigate this. A Japanese genome-wide analysis recently reported that common genetic variation in immunoglobulin mu-binding protein 2 (IGHMBP2) was associated with IgA nephropathy. We sought to replicate this using the new UK collection, and through an independent parallel analysis of a Han Chinese population.
  
  
  METHODS
  In the UK collection, haplotype-tagging (tag) single-nucleotide polymorphisms (SNPs) and haplotypes were analysed in a case-control study (349 cases, 605 controls) and family-based analysis (162 complete and 23 partially complete family trios), which was performed using the transmission disequilibrium test. In parallel, 663 cases of IgA nephropathy and 663 controls from a Chinese population were analysed: coding and flanking regions of the gene were re-sequenced in a subset, and SNP and haplotype association analysis was performed in the whole collection using the identified tagSNPs and all the coding and exonic flanking SNPs.
  
  
  RESULTS
  Case-control studies in UK and Chinese populations, and family-based tests in the UK population provided no evidence for association between variation in IGHMBP2 and IgA nephropathy. The A allele of SNP G34448A was not present in the UK collection. It was present but not associated with the disease in the Chinese population.
  
  
  CONCLUSIONS
  Variation in IGHMBP2 does not confer significant susceptibility to IgA nephropathy in UK Caucasian or Chinese Han populations.
authors.affiliation: Department of Nephrology, 3rd Affiliated Hospital, Center for Genome Research, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Tanqi
authors.initials: T
authors.lastname: Lou
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Gale
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Rees
authors.forename: Ben
authors.initials: B
authors.lastname: Rhodes
authors.forename: John
authors.initials: J
authors.lastname: Feehally
authors.forename: Caixia
authors.initials: C
authors.lastname: Li
authors.forename: Youji
authors.initials: Y
authors.lastname: Li
authors.forename: Ru
authors.initials: R
authors.lastname: Li
authors.forename: Weijun
authors.initials: W
authors.lastname: Huang
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.forename: Joseph C K
authors.initials: JC
authors.lastname: Leung
authors.forename: Man F
authors.initials: MF
authors.lastname: Lam
authors.forename: Kar N
authors.initials: KN
authors.lastname: Lai
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wang
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Maxwell
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D030541:Databases, Genetic; D005260:Female; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*; D006113:United Kingdom; D044465:White People / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C489892:IGHMBP2 protein, human; D014157:Transcription Factors