Abstract
IgA nephropathy (IgAN) is the most common chronic glomerular disease worldwide. Genetic factors are thought to be crucial in the pathogenesis of IgAN. However, few data are available on the relationship between human leucocyte antigen (HLA) and signal transducer and activator of transcription 4 (STAT4) polymorphisms and IgAN susceptibility in the Chinese population. Therefore, we examined HLA-DP/DQ and STAT4 polymorphisms (rs3077, rs9277535, rs7453920 and rs7574865) in a total of 630 subjects including 140 IgAN and 490 healthy controls in Chinese. There were significant associations between IgAN patients and healthy controls in the allele frequency of rs3077, rs9277535 and rs7574865. In addition, the genotypes of rs3077, rs9277535 and rs7574865 were also significantly associated with IgAN under recessive models. Moreover, the haplotypes block AAG, AGG, GAG and GGA in the HLA gene significantly correlated with the risk of IgAN. This is the first study demonstrating the significant associations of SNP rs3077, rs9277535 and rs7574865 and the haplotypes in the HLA gene with the risk of IgAN in a Southwest Chinese population. This research provides a new insight into the significant relationship between HLA-DP and STAT4 polymorphisms and the susceptibility to IgAN.
Highlights
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide [1]
immunoglobulin A (IgA) nephropathy (IgAN) is regarded as a complex disease that is initiated by more than one genetic factor combined with environmental factors [29]
The pathogenesis of IgAN is ambiguous, the associations between genes polymorphisms and IgAN susceptibility increase our understanding of the mechanisms
Summary
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide [1]. It is characterized by the deposition of IgA in glomerular mesangium and is diagnosed by immunohistochemical analysis on renal biopsies apart from other varying clinical manifestations [2]. It is noteworthy that human leucocyte antigen (HLA) region contains the strongest common susceptibility alleles that predispose to IgA nephropathy in the European population [16]. J., et al have identified that the gene polymorphisms of HLA-DPB1, HLA-DRB1 and HLA-DRA were associated with the susceptibility to IgAN www.impactjournals.com/oncotarget in a Chinese population [17,18,19]. We investigate the correlation of the SNP rs3077 in HLA-DPA1, rs9277535 in HLA-DPB1 and rs7453920 in HLA-DQB2 with the susceptibility to IgAN in this study
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