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Polymorphism of DEFA in Chinese Han population with IgA nephropathy

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Abstract

Our recent genome-wide association study (GWAS) had discovered a new locus at 8p23 (rs2738048) associated with IgA nephropathy (IgAN) in Chinese Han patients, implicating the DEFA gene family within this locus as susceptibility genes. However, it is still unknown whether there are additional variations within these genes associated with the disease susceptibility. The aim of this study is to investigate the polymorphisms of DEFA genes in the susceptibility to IgAN and explore possible disease mechanisms. Sixteen tag single-nucleotide polymorphisms (tag SNPs) were selected for association study in 1,000 IgAN cases and 1,000 controls by using Sequenom MassArray system or TaqMan SNP genotyping assays. We found seven SNPs within DEFA genes that were significantly associated with IgAN, including rs2738048 discovered in our previous GWAS (p = 0.0007, OR = 0.77) and additional 6 SNPs (rs2615787, p = 0.0001, OR = 0.74; rs2738081, p = 0.0003, OR = 0.72; rs2738058, p = 0.0001, OR = 0.73; rs4288398, p = 0.0008, OR = 0.78; rs6984215, p = 0.002, OR = 0.63; rs12716641, p = 0.00002, OR = 0.71). Electrophoretic mobility shift assays and luciferase assays demonstrated that fragments containing rs2738048, rs2738081 and rs6984215 were transcription factor binding sites for CTF, SP1 and CdxA, respectively, and the allele status of rs2738048 and rs6984215 could significantly change the luciferase activity. These results suggest that polymorphisms within DEFA genes are involved in gene transcriptional regulation, and this may have some effect in mediating susceptibility to IgAN in southern Chinese.

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Acknowledgments

We are grateful to all the subjects and healthy volunteers who participated in this work. We thank Jia-Nee Foo for reviewing the manuscript and providing constructive suggestions. This work was funded by Key Program of National Natural Science Foundation of China (81130012), National Natural Science Foundation of China for Distinguished Young Scholars (30925019), Young Scientists Fund of National Natural Science Foundation of China (81200489), Natural Science Foundation of Guangdong Province, China (S2012040006453) and Young Scholars Fund for the Doctoral Program of Higher Education of China (20120171120087).

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Authors and Affiliations

  1. Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou, 510080, Guangdong, China

    Ricong Xu, Shaozhen Feng, Zhijian Li, Peiran Yin, Zhen Ai, Wenting Liu, Xueqing Yu & Ming Li

  2. Guangdong Provincial Key Laboratory of Nephrology, Ministry of Health, Guangzhou, Guangdong, China

    Ricong Xu, Shaozhen Feng, Zhijian Li, Peiran Yin, Zhen Ai, Wenting Liu, Xueqing Yu & Ming Li

  3. Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China

    Yonggui Fu

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  1. Ricong Xu
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Correspondence to Ming Li.

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R. Xu and S. Feng contributed equally to this work.

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Xu, R., Feng, S., Li, Z. et al. Polymorphism of DEFA in Chinese Han population with IgA nephropathy. Hum Genet 133, 1299–1309 (2014). https://doi.org/10.1007/s00439-014-1464-y

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