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Cannabinoid Receptor Type 1 and mu-Opioid Receptor Polymorphisms Are Associated With Cyclic Vomiting Syndrome

Wasilewski, Andrzej, MSc1; Lewandowska, Urszula, PhD, DSc1; Mosinska, Paula, MSc1; Watala, Cezary2; Storr, Martin3,4; Fichna, Jakub, PhD, DSc1; Venkatesan, Thangam5

American Journal of Gastroenterology: June 2017 - Volume 112 - Issue 6 - p 933–939
doi: 10.1038/ajg.2017.73
ORIGINAL CONTRIBUTIONS: FUNCTIONAL GI DISORDERS
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Objectives: Cyclic vomiting syndrome (CVS) is a disorder defined by recurrent, unexplained episodes of severe nausea and vomiting. Our aim was to investigate whether CVS and pathophysiological mechanisms underlying this condition are associated with selected variations in genes encoding the components of the endogenous cannabinoid and opioid systems.

Methods: This case–control study included 65 patients with CVS-16 male and 49 female, and 1,092 healthy controls-525 male and 567 female from the 1000 Genomes Project. CVS subjects filled out study-specific questionnaires. Single-nucleotide polymorphisms (SNPs) in genes encoding cannabinoid receptors (CNR1andCNR2), fatty acid amide hydrolase (FAAH) and mu-opioid receptor (OPRM1) were analyzed using the TaqMan SNP genotyping assay. Correlations between SNP’s and clinical characteristics of CVS were ascertained.

Results: Our study disclosed an increased risk of CVS among individuals with AG and GG genotypes ofCNR1rs806380 (P<0.01), whereas the CC genotype ofCNR1rs806368 and AG and GG genotypes ofOPRM1rs1799971 were associated with a decreased risk of CVS (P<0.05). In addition, AG and GG genotypes ofOPRM1rs1799971 were correlated with migraine episodes, AG and GG ofOPRM1rs1799971, and CT and CC ofCNR1rs806368 with a family history of migraines (second degree relatives), and CT and CC ofCNR1rs2023239 with a positive response to therapy.

Conclusions: Our results show for the first time that the variations inCNR1andOPRM1genes are associated with CVS and that different genotypes may contribute to the risk of CVS.

1Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland

2Department of Haemostasis and Haemostatic Disorders, Chair of Biomedical Sciences, Medical University of Lodz, Lodz, Poland

3Center of Endoscopy, Starnberg, Germany

4Walter Brendel Center of Experimental Medicine, Ludwig Maximilians University of Munich, Munich, Germany

5Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA

Correspondence: Jakub Fichna, PhD, DSc, Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, Lodz 92-215, Poland. E-mail: jakub.fichna@umed.lodz.pl

Received 08 October 2016; accepted 01 February 2017

Guarantor of the article: Jakub Fichna, PhD, DSc.

Specific author contributions: Study concept and design: Martin Storr, Jakub Fichna, and Thangam Venkatesan; data acquisition: Andrzej Wasilewski, Urszula Lewandowska, and Paula Mosinska; analysis and interpretation of the data: Andrzej Wasilewski, Cezary Watala, Jakub Fichna, and Thangam Venkatesan; drafting of the manuscript: Andrzej Wasilewski, Martin Storr, Jakub Fichna, and Thangam Venkatesan;critical revision of the manuscript: all authors; all authors read and approved the final version of the manuscript.

Financial support: Supported by the Medical University of Lodz (503/1-156-04/503-11-001 to JF, 502-03/1-156-04/502-14-239 to A.W.), National Science Center (UMO-2013/11/B/NZ7/01301 and UMO-2014/13/B/NZ4/01179 to J.F.) and the Deutsche Forschungsgemeinschaft (DFG) to M.S.

Potential competing interests: None.

SUPPLEMENTARY MATERIAL is linked to the online version of the paper at http://www.nature.com/ajg

© The American College of Gastroenterology 2017. All Rights Reserved.
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