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J Gene Med. 2017 Jun;19(6-7). doi: 10.1002/jgm.2966.

Association of TNFSF13 polymorphisms with IgA nephropathy in a Chinese Han population.

Zhong Z1,2, Feng SZ1,2, Xu RC1,2,3, Li ZJ1,2, Huang FX1,2, Yin PR1,2, Liu WT1,2, Wang M1,2, Shi DC1,2, Zhou Q1,2, Yu XQ1,2, Li M1,2.

Author information

1
Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
2
Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, Guangdong, China.
3
Department of Nephrology, The First Affiliated Hospital, Shenzhen University, Shenzhen, Guangdong, China.

Abstract

BACKGROUND:

Our previous genome-wide association study of IgA nephropathy (IgAN) in a Chinese Han population suggested that the TNFSF13 gene may be a novel susceptibility gene for IgAN. In the present study, we aimed to further evaluate the associations of single-nucleotide polymorphisms (SNPs) and expression level of the 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 ratio (OR) and 95% confidence interval (95% CI) with adjustment for age and sex. Serum APRIL (encoded by the TNFSF13 gene) level was detected by an enzyme-linked immunosorbent assay.

RESULTS:

We found that rs3803800 was significantly associated with the susceptibility of IgAN after Bonferroni correction [padditive  = 0.0009, OR (95% CI) = 1.25 (1.09-1.42); precessive  = 0.0006, OR (95% CI) = 1.54 (1.20-1.96)]; however, the association remained only in women after further sex-stratified analysis. Genotype-phenotype correlation analysis showed significant associations of rs3803800 with severe clinicopathological manifestations in IgAN patients after adjusting for age and sex, as well as the other two SNPs (rs4246413 and rs4968210) that 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:

The results of the present study indicate that the genetic variations and gene expression level of TNFSF13 are associated with the susceptibility and severity of IgAN in a Han Chinese population.

KEYWORDS:

IgA nephropathy; TNFSF13; case-control study; gene expression; single-nucleotide polymorphisms

PMID:
28636766
DOI:
10.1002/jgm.2966
[Indexed for MEDLINE]

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