Association of TNFSF13 polymorphisms with IgA nephropathy in Chinese Han population
2017
Background
Our previous genome-wide association study (GWAS) of IgA nephropathy (IgAN) in Chinese Han population suggested that TNFSF13 gene may be a novel susceptibility gene for IgAN. In this study, we aim to further evaluate the associations of single-nucleotide polymorphisms (SNPs) and expression level of TNFSF13 gene with the risk and clinical parameters of IgAN.
Methods
Six candidate SNPs were selected for genotyping by Sequenom MassARRAY iPLEX in 1000 IgAN cases and 1000 controls. Unconditional logistic regression was used to calculate the Odds ratios (OR) and 95% confidence interval (95% CI) with adjustment for age and sex. Serum APRIL (encoded by TNFSF13 gene) level was detected by enzyme-linked immunosorbent assay (ELISA).
Results
We found that rs3803800 was significantly associated with the susceptibility of IgAN after Bonferroni correction (p additive = 0.0009, OR (95%CI) = 1.25 (1.09–1.42); p recessive = 0.0006, OR (95%CI) = 1.54 (1.20–1.96)), however, the association remained only in women after further gender-stratified analysis. Genotype-phenotype correlation analysis showed significant associations of rs3803800 with severe clinicopathological manifestations in IgAN patients after adjusting for age and gender, as well as the other two SNPs (rs4246413 and rs4968210) which were also associated with specific clinical phenotypes. Compared with healthy controls, serum APRIL levels were significantly higher in IgAN patients (p = 0.0001) and associated with severity of disease.
Conclusions
Our results indicated that the genetic variations and gene expression level of TNFSF13 were associated with the susceptibility and severity of IgAN in Han Chinese population.
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