Association of gene polymorphism of polymeric immunoglobulin receptor and IgA nephropathy

Objective In order to explore the possibility that genetic predisposition t o dysfunction of mucosal immunity and the IgA processing pathway plays a ro le in the pathogenesis of mesangial IgA1 deposition in IgAN, we examined th e possible association of the gene polymorphism. of pIgR in the patients wi th and without IgAN. Subjects and Methods Genomic DNA of peripheral blood cells was isolated fro m 372 individuals including 172 histologically confirmed IgAN patients. Seg ments of the pIgR gene were PCR amplified and restriction fragment length p olymorphism was determined as A1 and A2 with and without Pvu II site, respe ctively. Results The pIgR genotype distribution was significantly different between the patients with IgAN and those without IgAN. Allele frequency of A2 was h igher in IgAN than in other renal diseases (A1 and A2; 0.516 and 0.484 in I gAN, 0.641 and 0.359 in others, chi (2)=9.84, P=0.0017, Odds ratio=1.71). M oreover, the subjects with,A2A2 genotype were associated with a relatively low level of serum IgA only in the patients with IgAN but not in other rena l diseases. The difference of allele frequencies was more remarkable in the patients with a serum IgA level of less than 300 mg/dl (A1 and A2; 0.439 a nd 0.561 in IgAN, 0.702 and 0.298 in others, chi (2)=12.44, P=0.0004, Odds ratio=3.01). Conclusion This is the first demonstration of the pIgR gene polymorphisms i n IgAN which are associated with its clinical phenotype. Gene polymorphisms of pIgR may be candidate genetic markers of susceptibility to IgAN.