Association of BH3 interacting domain death agonist (BID) gene polymorphisms with proteinuria of immunoglobulin A nephropathy

Abstract

Background. Apoptosis plays an important role in the mechanism regulating the development of glomerulonephritis. We investigated whether polymorphisms of apoptotic genes such as B-cell CLL/lymphoma 2 (BCL2), BH3-interacting domain death agonist (BID), and caspase 8 (CASP8) were associated with immunoglobulin A nephropathy (IgAN) and with the clinical phenotypes of IgAN patients. Methods. We genotyped promoter and coding region single nucleotide polymorphisms (SNPs) (rs2279115 and rs1801018 for BCL2; rs8190315 and rs2072392 for BID; and rs6747918 and rs1045487 for CASP8) using direct sequencing in 195 IgAN patients and 289 control subjects. Results. No SNPs were associated with IgAN. However, in analysis of clinical phenotypes, we found that rs8190315 and rs2072392 of BID were associated with proteinuria levels of IgAN patients in additive (AG vs. GG vs. AA, p = 0.0008 for rs8190315; TC vs. CC vs. TT, p = 0.0012 for rs2072392) and dominant models (AG/GG vs. AA, p = 0.0014 for rs8190315; TC/CC vs. TT, p = 0.0031 for rs2072392). In particular, the frequencies of genotypes containing minor alleles of rs8190315 (G allele) and rs2072392 (C allele) were increased in IgAN patients with higher protienuria levels (> 40 mg/m2/h). Conclusion. These results suggest that BID may play a role in severe IgAN.