title: Family-based association study showing that immunoglobulin A nephropathy is associated with the polymorphisms 2093C and 2180T in the 3' untranslated region of the Megsin gene.
abstract: Immunoglobulin A nephropathy (IgAN) is considered to be a multifactorial disease with genetic and environmental factors contributing to its pathogenesis. The genes involved in susceptibility and progression of the disease have not yet been clearly elucidated. Megsin (SERPINB7) is an important candidate gene, predominantly expressed in glomerular mesangium and upregulated in IgAN. To investigate the potential role of this and other genes in IgAN, patients with biopsy-proven IgAN were recruited, as were family members, for a family-based association study. The genotypes of the polymorphisms C2093T and C2180T within the 3' untranslated region of the gene were determined by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. The results were analyzed by transmission disequilibrium test (TDT) and haplotype relative risk (HRR). TDT analyses revealed that Megsin 2093C and 2180T alleles were significantly more transmitted from heterozygous parents to patients than expected (C2093T: 127 trios, P = 0.034, C2180T: 100 trios, P = 0.002). Extended TDT showed increased cotransmission of the 2093C and 2180T alleles (232 families, P < 0.001). HRR revealed that the 2093C and 2180T alleles were more often transmitted to patients (P = 0.014, <0.001, respectively). Genetic variation in Megsin confers susceptibility to IgAN.
authors.affiliation: Department of Nephrology, 1st Affiliated Hospital, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: You-Ji
authors.initials: YJ
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Du
authors.forename: Cai-Xia
authors.initials: CX
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.forename: Joseph C K
authors.initials: JC
authors.lastname: Leung
authors.forename: Man F
authors.initials: MF
authors.lastname: Lam
authors.forename: Niansheng
authors.initials: N
authors.lastname: Yang
authors.forename: Fengxian
authors.initials: F
authors.lastname: Huang
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.forename: Ji-Qian
authors.initials: JQ
authors.lastname: Fang
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; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D018450:Disease Progression; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA; D015843:Serpins / Q000235:genetics* / Q000502:physiology*
chemical_list: D020413:3' Untranslated Regions; C114170:SERPINB7 protein, human; D015843:Serpins