title: Association of MEGSIN 2093C-2180T haplotype at the 3' untranslated region with disease severity and progression of IgA nephropathy.
abstract: BACKGROUND
  MEGSIN is a gene predominantly expressed in the renal mesangium, and is upregulated in IgA nephropathy (IgAN). Our previous study has shown that the 2093C and 2180T alleles at the 3' untranslated region (3'UTR) of the gene are associated with susceptibility to IgAN, but the relationships of these genetic variants with the clinical manifestations and renal histological lesions of IgAN have not been examined previously.
  
  
  METHODS
  302 IgAN patients followed up for 52.8+/-22.5 months were investigated. Haplotypes at the 3'UTR were constructed using the 2093C/T and 2180C/T alleles. The genotype-phenotype relationship was studied by correlations of haplotypes and the clinical data and renal histopathological changes.
  
  
  RESULTS
  The 2093C-2180T haplotype was present more often in patients with disease that progressed more rapidly (chi2((C-T/others)) = 8.429, P = 0.004), and was also correlated with hypertension (chi2((C-T/others)) = 6.459, P = 0.012), severe proteinuria (>or=2 g/d) (chi2((C-T/others)) = 6.332, P = 0.013), and Lee's class IV and V histological changes (chi2((C-T/others)) = 9.640, P = 0.008).
  
  
  CONCLUSIONS
  In this Chinese population, the 2093C-2180T haplotype at the 3'UTR of MEGSIN gene is associated with more severe forms of IgAN, and more rapid disease progression. This provides further evidence for the involvement of genetic variations of MEGSIN in the pathogenesis of IgAN.
authors.affiliation: Department of Nephrology, First Affiliated Hospital, Medical College, Sun Yat-Sen University, 74 Zhongshan Road II, Guangzhou 510089, PR China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Xia
authors.forename: Youji
authors.initials: Y
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Du
authors.forename: Niansheng
authors.initials: N
authors.lastname: Yang
authors.forename: Caixia
authors.initials: C
authors.lastname: Li
authors.forename: Joseph C K
authors.initials: JC
authors.lastname: Leung
authors.forename: Man F
authors.initials: MF
authors.lastname: Lam
authors.forename: Weijun
authors.initials: W
authors.lastname: Huang
authors.forename: Suqin
authors.initials: S
authors.lastname: Chen
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Maxwell
authors.forename: Kar N
authors.initials: KN
authors.lastname: Lai
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D002681:China / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005922:Glomerulonephritis, IGA / Q000175:diagnosis* / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D006973:Hypertension; D008297:Male; D011507:Proteinuria; D015843:Serpins / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D020413:3' Untranslated Regions; C114170:SERPINB7 protein, human; D015843:Serpins