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Identification of genetic loci stratified by diabetic status and microRNA related SNPs influencing kidney function in Korean populations

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Abstract

Chronic kidney disease (CKD) is characterized by a progressive loss of kidney function over a period of months or years. It is estimated that about 7.2 % of adults over the age of 30 have CKD worldwide. Although one of the major risk factors of CKD is family history, the heritability of CKD is not fully understood. It is also known that the diabetic condition is highly influential on the onset of CKD. To understand the genetic bases of CKD that remain unidentified, we performed genetic association analyses for kidney function-related traits such as blood urea nitrogen (BUN) and albumin in subjects stratified by diabetic status. In the discovery stage of the study, we used genome-wide scan data and clinical data in about 8800 subjects from the Korean Association Resource (KARE) project. Health2 study data comprising about 1800 subjects were used for the replication stage. Our two stage association analyses demonstrated that the LOC105374266 locus (rs9820070) showed strong evidence of association with BUN (P = 8.47 × 10−14) in nondiabetic normal subjects (n = ~4300). To extend our knowledge of the genetic determinants influencing kidney function, we also analyzed the association between kidney function-related traits and microRNA related variants. For this analysis, miRNA related SNPs were selected from KARE and Health2 cohort genotype data. Our study suggests the potential relevance of miRNA to the kidney function (miR-518b for BUN; miR-146a and miR-1295a for albumin) in Korean populations.

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Acknowledgments

This study was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MEST) (2012M3A9D1054534) and Hallym University Research Fund 2012 (HRF-201203-008). This study obtained biospecimens and data from the Korean Genome Analysis Project (4845-301), the Korean Genome and Epidemiology Study (4851-302), and Korea Biobank Project (4851-307, KBP-2015-029), which were supported by the Korea Center for Disease Control and Prevention, Republic of Korea.

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Authors and Affiliations

  1. Department of Biomedical Science, Hallym University, Chuncheon, Gangwon-do, Republic of Korea

    Jisun Lim & Yoon Shin Cho

  2. Department of Biomedical Informatics, Hanyang University, Seoul, Republic of Korea

    InSong Koh

  3. Department of Physiology, College of Medicine, Hanyang University, Seoul, Republic of Korea

    InSong Koh

Authors
  1. Jisun Lim
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  2. InSong Koh
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  3. Yoon Shin Cho
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Corresponding author

Correspondence to Yoon Shin Cho.

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The authors declare no conflicts of interest.

Ethical statement

In this study, genetic and epidemiological data were provided by the Korea Center for Disease Control and Prevention, Republic of Korea. This study was approved by the Hallym University Institutional Review Board (HIRB-2015-028).

Electronic supplementary material

Below is the link to the electronic supplementary material.

13258_2016_411_MOESM1_ESM.xlsx

Supplementary material 1. The list of SNPs identified in human microRNAs. A total of 612 SNPs in human pre-miRNAs were selected from a microRNA-related SNP database (http://www.bioguo.org/miRNASNP/) (XLSX 48 kb)

13258_2016_411_MOESM2_ESM.xlsx

Supplementary material 2. The list of SNPs identified in the 1 kb flanking region of human microRNAs. A total of 18,442 SNPs in human miRNA flanks (1 kb) were selected from a microRNA-related SNP database (http://www.bioguo.org/miRNASNP/) (XLSX 839 kb)

13258_2016_411_MOESM3_ESM.docx

Supplementary material 3. Genetic variants associated with BUN or blood albumin that were identified from previous studies. The allele that increased BUN or that decreased blood albumin was defined as the reference allele (RA) and is indicated on the basis of the forward strand of NCBI Build 36. The effect size of RA on natural log-transformed values of BUN or non-transformed values of albumin concentration. EA, East Asians; na, not available (DOCX 19 kb)

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Lim, J., Koh, I. & Cho, Y.S. Identification of genetic loci stratified by diabetic status and microRNA related SNPs influencing kidney function in Korean populations. Genes Genom 38, 601–609 (2016). https://doi.org/10.1007/s13258-016-0411-9

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  • DOI: https://doi.org/10.1007/s13258-016-0411-9

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