Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2020; 26(18): 2194-2202
Published online May 14, 2020. doi: 10.3748/wjg.v26.i18.2194
Genetic association analysis of CLEC5A and CLEC7A gene single-nucleotide polymorphisms and Crohn’s disease
Nagi Elleisy, Sarah Rohde, Astrid Huth, Nicole Gittel, Änne Glass, Steffen Möller, Georg Lamprecht, Holger Schäffler, Robert Jaster
Nagi Elleisy, Sarah Rohde, Astrid Huth, Nicole Gittel, Georg Lamprecht, Holger Schäffler, Robert Jaster, Department of Medicine II, Division of Gastroenterology, Rostock University Medical Center, Rostock 18057, Germany
Änne Glass, Steffen Möller, Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock 18057, Germany
Author contributions: Schäffler H, Rohde S and Jaster R designed the study; Huth A, Schäffler H and Lamprecht G took reponsibility for patient care and follow-up; Elleisy N, Rohde S and Jaster R performed the experiments; Gittel N, Huth A and Schäffler H collected the samples and performed the clinical characterisation of the patients; Elleisy N, Glass Ä, Möller S and Jaster R performed the biostatistics; all authors analyzed the data; Schäffler H and Jaster R wrote the manuscript and contributed equally and share senior authorship.
Supported by the Damp-Foundation, No. 2016-04.
Institutional review board statement: The study was approved by the ethic board of the Medical Faculty of the University of Rostock (A 2017-0137). Written informed consent was obtained from each participant prior to enrollment.
Conflict-of-interest statement: The authors declare that there is no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Robert Jaster, MD, Academic Research, Professor, Senior Postdoctoral Fellow, Senior Scientist, Department of Medicine II, Division of Gastroenterology, Rostock University Medical Center, E.-Heydemann-Str. 6, Rostock 18057, Germany. robert.jaster@med.uni-rostock.de
Received: February 4, 2020
Peer-review started: February 4, 2020
First decision: March 21, 2020
Revised: April 13, 2020
Accepted: April 29, 2020
Article in press: April 29, 2020
Published online: May 14, 2020
Processing time: 99 Days and 15.9 Hours
Abstract
BACKGROUND

Crohn’s disease (CD) is characterized by a multifactorial etiology and a significant impact of genetic traits. While NOD2 mutations represent well established risk factors of CD, the role of other genes is incompletely understood.

AIM

To challenge the hypothesis that single nucleotide polymorphisms (SNPs) in the genes CLEC5A and CLEC7A, two members of the C-type lectin domain family of pattern recognition receptors, may be associated with CD.

METHODS

SNPs in CLEC5A, CLEC7A and the known CD risk gene NOD2 were studied using real time PCR-based SNP assays. Therefore, DNA samples from 175 patients and 157 healthy donors were employed. Genotyping data were correlated with clinical characteristics of the patients and the results of gene expression data analyses.

RESULTS

In accordance with previous studies, rs2066844 and rs2066847 in NOD2 were found to be significantly associated with CD (allelic P values = 0.0368 and 0.0474, respectively). Intriguingly, for genotype AA of rs1285933 in CLEC5A, a potential association with CD (recessive P = 0.0523; odds ratio = 1.90) was observed. There were no associations between CD and SNPs rs2078178 and rs16910631 in CLEC7A. Variants of rs1285933 had no impact on CLEC5A gene expression. In contrast, genotype-dependent differences of CXCL5 expression in peripheral blood mononuclear cells were observed. There is no statistical interaction between the tested SNPs of NOD2 and CLEC5A, suggesting of a novel pathway contributing to the disease.

CONCLUSION

Our data encourage enlarged follow-up studies to further address an association of SNP rs1285933 in CLEC5A with CD. The C-type lectin domain family member also deserves attention regarding a potential role in the pathophysiology of CD.

Keywords: Crohn’s disease; Single nucleotide polymorphisms; NOD2; CLEC5A; Gene expression; CXCL5

Core tip: The genetic traits of Crohn’s disease (CD) are incompletely understood. Here, we report a potential association of single nucleotide polymorphism (SNP) rs1285933 in CLEC5A, a member of the C-type lectin domain family of pattern recognition receptors, with CD. Variants of SNP rs1285933 had no impact on CLEC5A gene expression in peripheral blood mononuclear cells but correlated with the expression of CXCL5. The SNPs rs2078178 and rs16910631 in CLEC7A were not associated with the disease. The role of CLEC5A in the pathophysiology of CD deserves further attention.