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Functional mechanisms for diabetic nephropathy-associated genetic variants

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Abstract

Diabetic nephropathy (DN) is one of the major complications of diabetes. A tremendous amount of genetic variations have been identified to be associated with DN. However, most of them only generate from statistical associations at the DNA level, generally without direct functional evidence regarding their association mechanisms underlying DN. Based on the publicly available datasets and resources, this study performed integrative analyses (expression quantitative trait loci analysis, differential gene expression analysis and functional prediction analysis) to detect the molecular functional mechanisms underlying the associations for DN. Among 150 selected (P < E-4) genetic associations that were archived in the public databases, two single nucleotide polymorphisms (SNPs) (rs3135377 and rs9469220) have been found to act as cis-effect regulators of the “identified” gene (HLA-DRA and HLA-DRB1). These eQTL genes have differential expression signals in the DN-associated cell groups. These SNPs were predicted as regulatory sites by utilizing online prediction tools. Our data suggest potential mechanistic links underlying the association between DN and two identified SNPs. These results could help us to have a deeper understanding of the functional relevance of genetic variants with susceptibility to DN, which is useful for pursuit of in-depth validation studies to dissect their involvements and molecular functional mechanisms in DN.

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Acknowledgments

This work was supported by the grants (NOS. 81302501 and 81560529)from National Natural Science Foundation of China, the grants (NOS.20151BBG70249, 20122BAB215005 and 20132BAB215005) from Natural Science Foundation of Jiangxi Province, the grant (NO.GJJ14093) from the Foundation of the Education Department of Jiangxi Province, the grant (NO.20155643) from the Foundation of the Health Department of Jiangxi Province, and the grant (NOS. 201410403132, 201510403039, YC2015-S041, 20140611, 2015195 and 14001840) from Nanchang university Students’ innovation and entrepreneurship training program.

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    Authors and Affiliations

    1. Department of Physiology, JiangXi Medical College of Nanchang University, 461 Bayi Road, Donghu District, Nanchang, Jiangxi, China

      Chengxin Gong, Luling He, Changle Liu, Shenqiang Rao, Shangdong Liang & Hong Xu

    2. Department of Nursing, Fuzhou Medical College of Nanchang University, Fuzhou, Jiangxi, China

      Chaopeng Xiong

    3. Department of Pathology, Jiangxi Medical College of Nanchang University, Nanchang, Jiangxi, China

      Wen Xiao

    4. Department of Clinic Medicine, Jiangxi Medical College of Nanchang University, Nanchang, Jiangxi, China

      Yonghu Xu, Yongfang Fan, Xingzi Liu, Lu Ding, Lan Tang, Fangfang Hu, Mengqi Xiong & Mei Yang

    5. School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, China

      Chengxin Gong

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    1. Chengxin Gong
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    Correspondence to Hong Xu.

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    Chengxin Gong and Chaopeng Xiong contributed equally to this study.

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    Cite this article

    Gong, C., Xu, Y., Fan, Y. et al. Functional mechanisms for diabetic nephropathy-associated genetic variants. Genes Genom 38, 595–600 (2016). https://doi.org/10.1007/s13258-016-0415-5

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