Variants of C1GALT1 gene are associated with the genetic susceptibility to IgA nephropathy

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 beta 3-Gal-T, and its chaperone, Cosmc, play important roles in beta 1,3 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 -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.