3'UTR variants of TNS3, PHLDB1, NTN4, and GNG2 genes are associated with IgA nephropathy risk in Chinese Han population.

BACKGROUND:Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis and is characterized by mesangial cell proliferation and agglomeration of the mesangial matrix. METHODS:In this study, we aimed to explore the role of TNS3, PHLDB1, NTN4, and GNG2 3'untranslated region (3'UTR) polymorphisms with the risk of IgAN in a Chinese Han cohort. A logistic recession model was used to calculate the effects of candidate single nucleotide polymorphism (SNP) on IgAN risk after adjusting age and gender difference. In silico prediction was conducted to identify potential functions of SNPs. RESULTS:The analysis revealed a significant relationship between the homozygotic genotype for NTN4 rs1362970 A/A and higher risk of IgAN (p = 0.003). Statistically significant associations were found when the sample was stratified by gender and Lee's grade. As a result, NTN4 rs1362970 A/A and GNG2 rs3204008 G/G genotypes were associated with enhanced IgAN risk in males (p = 0.006, p = 0.023, respectively), and the association between the PHLDB1 rs7389 G/T genotype and higher IgAN risk was found in females (p = 0.008). In the Lee's grade III-V subgroup, the rs1369270 in NTN4 was significantly correlated with the risk of IgAN (p = 0.004). Bioinformatics prediction suggested that rs1362970 within NTN4 3'UTR was located in the potential target sequence of miR-483-5p. CONCLUSIONS:Our research confirmed that NTN4, GNG2, and PHLDB1 gene polymorphisms were implicated in IgAN susceptibility in Chinese Han population. Further research should be conducted to investigate and validate the mechanism by which the above-mentioned polymorphisms affect IgAN.

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