Human Leukocyte Antigen <i>DRB1</i> Alleles Predict Risk and Disease Progression of Immunoglobulin A Nephropathy in Han Chinese

Abstract

The role of human leukocyte antigen (HLA) class II polymorphisms in the pathogenesis and progression of primary immunoglobulin A nephropathy (pIgAN) is unclear. This study aimed to explore the relationship of HLA-DRB1 alleles with the susceptibility and disease progression of pIgAN in Han Chinese. A PCR-based genotyping technique was used to detect HLA-DRB1 alleles in 139 patients with pIgAN and 143 healthy subjects. A total of 37 HLA-DRB1 alleles were detected, of which 30 were found in pIgAN patients and 29 in healthy subjects. In pIgAN patients, the frequencies of HLA-DRB1*140501 (belonging to DR*14) were significantly increased, while the frequencies of HLA-DRB1*070101 (belonging to DR*7) were significantly reduced compared with the healthy individuals. Further stratification analysis revealed that the frequencies of HLA-DRB1*030101 in pIgAN patients with normal renal function were significantly higher than those in patients with renal dysfunction. These findings suggest that HLA-DRB1 polymorphisms are related to the occurrence and disease progression of pIgAN patients in Han Chinese, with HLA-DRB1*140501 being a susceptible allele and HLA-DRB1*070101 a resistant allele. HLA-DRB1*030101 may serve as a predictor of disease progression and renal damage of pIgAN in Han Chinese. Further studies are warranted to explore the immunological mechanisms for the genotype-disease phenotype relationship.

IgA Nephropathy Susceptibility Loci and Disease Progression

“…HLA-DR/DQ, coding for MHC II molecules and involved in antigen presentation, was detected by all five GWAS regardless of racial origins (7)(8)(9)(10)(11). HLA-DRB1 classic alleles have been reported to be related to disease progression in a Chinese IgA nephropathy cohort (37). In this study, we determined patients carrying rs2856717-T had an increased risk for disease progression.…”

Replication of genome‐wide association study identified seven susceptibility genes, affirming the effect of rs2856717 on renal function and poor outcome of IgA nephropathy

“…It is known that IgA antibody‐mediated immune response is T‐cell dependant, and the HLA class‐II products coded by DP, DQ, and DR genes affect antigen presentation to particular T cells . Reports from Hong Kong, Taiwan, Guangdong, and Sichuan have revealed HLA ‐family genetic variants to be associated with the genetic susceptibility of IgAN or a special subgroup of IgAN . It has already been reported that there is an association between HLA‐DRB1 polymorphisms and IgAN in the Han Chinese; HLA‐DRB1 * 140501 confers susceptibility, while HLA‐DRB1 * 070101 confers resistance.…”

The genetic variants at the HLA-DRB1 gene are associated with primary IgA nephropathy in Han Chinese

“…HLA-DRB1*140501 was reported to be a susceptible allele, and HLA-DRB1*070101 was reported to be a resistant allele. HLA-DRB1*030101 may serve as a predictor of disease progression and renal damage of primary IgAN in Han Chinese [ 29 ]. However, previous studies did not substantiate the conclusion that HLA-DRB1 was significantly associated with IgAN because a small number of samples were included in these studies and there was no association between the HLA-DR antigen and primary IgAN in Taiwanese Chinese [ 20 ].…”