Association of HLA-DR/DQ alleles and haplotypes with nephrotic syndrome

BackgroundNephrotic syndrome (NS) is a debilitating renal problem in children resulting from an interaction between environmental and genetic factors including human leukocyte antigen genes (HLA). The aim of this work was to study the probable link between HLA alleles/haplotypes and NS in south India. MethodsHLA DRB1*/DQB1* alleles were genotyped in 183 NS (76 steroid sensitive-SSNS; 107 steroid resistant-SRNS) and paediatric healthy controls (PHCs; n=91) using polymerase chain reaction-sequence specific primers (PCR-SSP). HLA-A/-B genotyping was performed for patients (n=70) positive for DRB1*07-DQB1*02 haplotype to identify four locus extended haplotype. ResultsThe following alleles and haplotypes were strongly associated with NS (P<0.05 as significant): DRB1*07 (SSNS, P<7.98x10(-6); SRNS, P<0.008), DQB1*02 (SSNS, P<3.99x10(-6); SRNS, P<0.002), DRB1*07-DQB1*02 (SSNS, P<1.32x10(-4); SRNS, P<0.010), DRB1*07-DQB1*0301,0304 (DQ7) (SSNS, P<0.001) and DRB1*03-DQB1*02 (SRNS, P<0.048). Protective associations were observed for alleles DRB1*10 (SRNS, P<0.013), DQB1*05 (SSNS, P<4.34x10(-6); SRNS, P<0.01), DQB1*06 (SSNS, P<0.003), and haplotypes DRB1*10-DQB1*06 (SSNS, P<0.046; SRNS, P<0.032) and DRB1*15-DQB1*05 (SSNS, P<0.018). HLA-A/-B typing of 70 NS cases with two locus haplotype DRB1*07-DQB1*02 (70/183; 38.25%) revealed the presence of an extended haplotype A*03-B*07-DRB1*07-DQB1*02' (n=35; 50%). ConclusionOur study revealed strong susceptible association of DRB1*07 with SRNS and DQB1*02 with SSNS. A gender predominant protective association was observed for DRB1*10 with SRNS females; DQB1*05 with SSNS and SRNS males. Further, the study documented the presence of an extended haplotype and pleiotropic action of DRB1*/DQB1* alleles in immune-mediated aetiology of NS in south India. Summary at a Glance This study examined the link between HLA alles and nephrotic syndrome (NS), and showed the suscceptible associatrion of two-locus haplotype with NS. The results oberved in this manuscript will provide a meaningful information in the field of nephrology.