Open Access

Bioinformatics analysis of genetic variants of endoplasmic reticulum aminopeptidase 1 in ankylosing spondylitis

  • Authors:
    • Xiaoli Wang
    • Jie Ma
    • Jianbing Ma
    • Yurong Wen
    • Liesu Meng
    • Hao Yang
    • Rui Zhang
    • Dingjun Hao
  • View Affiliations

  • Published online on: August 31, 2017     https://doi.org/10.3892/mmr.2017.7417
  • Pages: 6532-6543
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

According to the results of the first genome-wide association study of ankylosing spondylitis (AS), endoplasmic reticulum aminopeptidase 1 (ERAP1) may serve an important role. However, a number of case-control studies have not been able to replicate this result using the same genetic markers. In the present study, the role of common genetic variants of ERAP1 in AS was investigated using two-stage bioinformatics analysis. In the first stage, a classical meta-analysis was performed to assess AS susceptibility markers in ERAP1 using data from available published case-control association studies. The summary odds ratios for 10 single nucleotide polymorphisms (SNPs) were observed to be statistically significant in different studies. In the second stage, the functional effects of these genetic ERAP1 variants were investigated using prediction tools and structural analyses. The K528R (rs30187) substitution SNP in ERAP1 was termed as likely damaging by PolyPhen-2 software, was observed to be located close to the entrance of the substrate pocket, and was predicted to contribute to reduced ERAP1 aminopeptidase activity. In addition, the R725Q (rs17482078) SNP, which was an additional potentially damaging substitution, was suggested to decrease the enzymatic activity of ERAP1, as this substitution may lead to the loss of two hydrogen bonds between R725 and D766 and affect the stability of the C-terminus of ERAP1. In conclusion, the results of the two-stage bioinformatics analysis supported the hypothesis that ERAP1 may present an important susceptibility gene for AS. In addition, the results revealed that two functional SNPs (rs30187 and rs17482078) demonstrated the potential to decrease the enzymatic activity of ERAP1 by affecting its protein structure. Further protein structure-guided studies of the specificity and activity of these ERAP1 variants are therefore warranted.
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November-2017
Volume 16 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Wang X, Ma J, Ma J, Wen Y, Meng L, Yang H, Zhang R and Hao D: Bioinformatics analysis of genetic variants of endoplasmic reticulum aminopeptidase 1 in ankylosing spondylitis. Mol Med Rep 16: 6532-6543, 2017
APA
Wang, X., Ma, J., Ma, J., Wen, Y., Meng, L., Yang, H. ... Hao, D. (2017). Bioinformatics analysis of genetic variants of endoplasmic reticulum aminopeptidase 1 in ankylosing spondylitis. Molecular Medicine Reports, 16, 6532-6543. https://doi.org/10.3892/mmr.2017.7417
MLA
Wang, X., Ma, J., Ma, J., Wen, Y., Meng, L., Yang, H., Zhang, R., Hao, D."Bioinformatics analysis of genetic variants of endoplasmic reticulum aminopeptidase 1 in ankylosing spondylitis". Molecular Medicine Reports 16.5 (2017): 6532-6543.
Chicago
Wang, X., Ma, J., Ma, J., Wen, Y., Meng, L., Yang, H., Zhang, R., Hao, D."Bioinformatics analysis of genetic variants of endoplasmic reticulum aminopeptidase 1 in ankylosing spondylitis". Molecular Medicine Reports 16, no. 5 (2017): 6532-6543. https://doi.org/10.3892/mmr.2017.7417