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DEFA gene variants associated with IgA nephropathy in a Chinese population

Genes & Immunity volume 16, pages 231–237 (2015)Cite this article

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Abstract

IgA nephropathy (IgAN) is a complex syndrome with high genetic heterogeneity. More recently, a genome-wide association study (GWAS) from Southern Han population revealed that variants within 8p23.1, where the DEFA genes encoding a-defensins assembled, were associated with susceptibility to IgAN. To replicate the association and fine-map the genetic variants, a case–control genetic study from an independent Northern Han cohort was conducted. A total of 60 single-nucleotide polymorphisms in a region spanning 350 kb encompassing the DEFA genes cluster were analyzed in 2096 individuals. Copy number variations of DEFA1A3 within the loci were also checked for the independent association. Functional significance of the associated variants was further examined by the in silico method as well as by cis-acting expression quantitative trait loci analysis with mRNA. It showed that 17 out of 60 (28.3%) variants were associated with susceptibility to IgAN. Two independent signals with functional potentials were discovered (rs2738058, P=4.64 × 10−5, odds ratio (OR)=0.76, 95% confidence interval (CI) 0.66–0.87 and rs9644778, P=4.78 × 10−3, OR=1.21, 95% CI 1.06–1.39). Besides, marginally significant association of rs9644778 risk genotype with lower proportion of gross hematuria (CC+CA vs AA 35.2% vs 30.2%, P=0.073) was observed. In conclusion, DEFA gene polymorphisms have potentially pathogenic roles in IgAN, and the role of mucosal immunity in the pathogenesis of IgAN has to be emphasized.

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Acknowledgements

We thank our collaborators of Ali G Gharavi from the Department of Medicine, Columbia University College of Physicians and Surgeons, New York City, NY, USA, for genotyping sorting and assistance. We also thank all the members of the laboratory for technical assistance and the patients and their families for their cooperation and for giving consent to participate in this study. This work was supported by grants from the National Natural Science Foundation of China (No. 81200524), The Foundation of Ministry of Education of China (20120001120008), Major State Basic Research Development Program of China (973 program, No. 2012CB517700), Research Fund of Beijing Municipal Science and Technology for the Outstanding PhD Program (20121000110) and Natural Science Fund of China to the Innovation Research Group (81321064).

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Authors and Affiliations

  1. Renal Division, Peking University First Hospital, Beijing, People’s Republic of China

    Y Y Qi, X J Zhou, F J Cheng, P Hou, L Zhu, S F Shi, L J Liu, J C Lv & H Zhang

  2. Peking University Institute of Nephrology, Beijing, People’s Republic of China

    Y Y Qi, X J Zhou, F J Cheng, P Hou, L Zhu, S F Shi, L J Liu, J C Lv & H Zhang

  3. Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, People's Republic of China

    Y Y Qi, X J Zhou, F J Cheng, P Hou, L Zhu, S F Shi, L J Liu, J C Lv & H Zhang

  4. Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, People’s Republic of China

    Y Y Qi, X J Zhou, F J Cheng, P Hou, L Zhu, S F Shi, L J Liu, J C Lv & H Zhang

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Qi, Y., Zhou, X., Cheng, F. et al. DEFA gene variants associated with IgA nephropathy in a Chinese population. Genes Immun 16, 231–237 (2015). https://doi.org/10.1038/gene.2015.1

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