Association of TNFSF13 polymorphisms with IgA nephropathy in a Chinese Han population
Association of TNFSF13 polymorphisms with IgA nephropathy in a Chinese Han population
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TNFSF13多态性与中国汉族人群IgA肾病的相关性
DOI：
10.1002/jgm.2966
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发表时间：
2017-06-01
影响因子：
3.5
通讯作者：
Li, Ming
中科院分区：
文献类型：
--
作者：
Zhong, Zhong;Feng, Shao-Zhen;Li, Ming
背景资料：我们先前在中国汉族人群中进行的伊加肾病（IgAN）全基因组关联研究表明，TNFSF 13基因可能是IgAN的一个新的易感基因。在本研究中，我们的目的是进一步评估单核苷酸多态性（SNPs）和TNFSF 13基因的表达水平与IgAN.Methods的风险和临床参数的关联：选择6个候选SNPs基因分型的Sequenom MassARRAY iPLEX在1000例IgAN和1000对照。采用非条件Logistic回归计算OR和95%可信区间（95%CI），并校正年龄和性别。血清APRIL结果：经Bonferroni校正后发现rs3803800与IgAN的易感性显著相关[p（相加）= 0.0009，OR（95%CI）= 1.25（1.09-1.42）; p（隐性）= 0.0006，OR（95%CI）= 1.54（1.20-1.96）];然而，在进一步的性别分层分析后，仅在女性中存在相关性。基因型-表型相关性分析显示rs3803800与IgAN患者在调整年龄和性别后的严重临床病理表现显著相关，另外两个SNP（rs 4246413和rs 4968210）也与特定的临床表型相关。与健康对照组相比，血清APRIL水平显着较高的IgA肾病患者（p = 0.0001），并与疾病的严重程度。结论：本研究的结果表明，TNFSF 13的遗传变异和基因表达水平与IgA肾病的易感性和严重程度在中国汉族人群。
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 [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 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.