title: Variants of C1GALT1 gene are associated with the genetic susceptibility to IgA nephropathy.
abstract: IgA nephropathy (IgAN) is a polygenic disorder and the precise role of genetic factors remains elusive. Increasing evidences have implicated the aberrant galactosylation of IgA1 molecules in the pathogenesis of IgAN. The galactosyltransferase, core 1 beta3-Gal-T, and its chaperone, Cosmc, play important roles in beta1,3 glycosylation of IgA1 molecule. A case-control association study was performed to investigate the association between single-nucleotide polymorphisms (SNPs) of C1GALT1 and C1GALT1C1 genes and the susceptibility to IgAN. A total of 1164 subjects were enrolled, including 670 IgAN patients and 494 geographically matched healthy controls. Five SNPs, -734C/T, -465A/G, -330G/T, -292C/-, and 1365G/A in C1GALT1 were selected as tagging SNPs. The D allele and DD genotype of -292C/- in IgAN patients were significantly lower than in the controls (P<0.01). The frequency of haplotype YATIG (Y=C or T) was significantly lower in patients than in controls (0.0719 vs 0.1168, P=2.775 x 10(-4), odds ratio (OR)=0.70). The haplotype YAGDA (0.1236 vs 0.0791, P=3.815 x 10(-3), OR=1.77) and YATDG (0.0840 vs 0.0298, P=1.258 x 10(-5), OR=3.03) were significantly higher in patients than in controls. The present study suggested that the polymorphisms of C1GALT1 gene were associated with the genetic susceptibility to IgAN in Chinese population.
authors.affiliation: Renal Division, Department of Internal Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China.
authors.forename: G-S
authors.initials: GS
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: J-C
authors.initials: JC
authors.lastname: Lv
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.forename: H-Y
authors.initials: HY
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005700:Galactosyltransferases / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006031:Glycosylation; D006239:Haplotypes; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D007070:Immunoglobulin A; C505293:C1GALT1 protein, human; D005700:Galactosyltransferases