Polymorphisms in oxidative pathway related genes and susceptibility to inflammatory bowel disease

doi:10.3748/wjg.v23.i47.8300

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World Journal of Gastroenterology

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World J Gastroenterol. Dec 21, 2017; 23(47): 8300-8307
Published online Dec 21, 2017. doi: 10.3748/wjg.v23.i47.8300

Polymorphisms in oxidative pathway related genes and susceptibility to inflammatory bowel disease

Nezha Senhaji, Sellama Nadifi, Younes Zaid, Aurora Serrano, Daniel Arturo Leon Rodriguez, Nadia Serbati, Mehdi Karkouri, Wafaa Badre, Javier Martín

Nezha Senhaji, Sellama Nadifi, Nadia Serbati, Laboratory of Genetic and Molecular Pathology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University, Casablanca 20100, Morocco

Younes Zaid, Mohammed VI University of Health Sciences, Casablanca 20000, Morocco

Aurora Serrano, Daniel Arturo Leon Rodriguez, Javier Martín, Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, P.T.S. Granada 18016, Spain

Mehdi Karkouri, Department of Pathology, CHU Ibn Rochd, Casablanca 20000, Morocco

Wafaa Badre, Department of Gastroenterology, CHU Ibn Rochd, Casablanca 20000, Morocco

Author contributions: Senhaji N carried out the molecular genetics studies, participated in the recruitment of patients and drafted the manuscript; Nadifi S conceived the study and participated in its design and coordination; Zaid Y has been involved in revising the manuscript. Serrano A participated in the molecular genetics study; Rodriguez DAL helped in the statistical analysis; Serbati N participated in the recruitment of patients and clinical data collection; Karkouri M and Badre W coordinated patients’ recruitment and provided the clinical data; Martín J conceived the study and revised the manuscript; all authors read and approved the final manuscript.

Institutional review board statement: The ethics committee of the Faculty of Medicine and Pharmacy of Casablanca approved the study in accordance with the declaration of Helsinki for experiments involving humans.

Conflict-of-interest statement: The authors declare that there are no conflicts of interest.

Data sharing statement: The datasets supporting the conclusions of this article are included within the article.

Correspondence to: Nezha Senhaji, PhD, Laboratory of Genetics and Molecular Pathology, Faculty of Medicine and Pharmacy of Casablanca, University Hassan II. 19, rue Tarik Ibnou Ziad, Faculté de Médecine et de Pharmacie, Casablanca 20100, Morocco. nezha.senhaji05@etude.univcasa.ma

Telephone: +212-6-65896590

Received: March 25, 2017
Peer-review started: March 29, 2017
First decision: April 21, 2017
Revised: May 14, 2017
Accepted: June 1, 2017
Article in press: June 1, 2017
Published online: December 21, 2017
Processing time: 271 Days and 2.9 Hours

Abstract

AIM

To investigate whether common variants in the oxidative pathway genes influence inflammatory bowel disease (IBD) risk among Moroccan patients.

METHODS

The distribution of (TAAA)n_rs12720460 and (CCTTT)n _rs3833912 NOS2A microsatellite repeats, HIF-1A_rs11549467 and NFKB1-94ins/delATTG_rs28362491 was analyzed in 507 subjects grouped in 199 IBD and 308 healthy controls. Genotyping was performed with polymerase chain reaction-fluorescent method and the TaqMan^® allelic discrimination technology.

RESULTS

The allele and genotype frequencies of HIF1A_ rs11549467, NFKB1_rs28362491 and NOS2A_ (TAAA)n did not differ significantly between patients and controls. Analysis of NOS2A_ (CCTTT)n markers evidenced differences between patients and healthy controls. A preferential presence of the (CCTTT)8 (P = 0.02; OR = 1.71, 95%CI: 1.07-2.74), (CCTTT)14 (P = 0.02; OR = 1.71, 95%CI: 1.06-2.76) alleles in IBD, (CCTTT)8 (P = 0.008; OR = 1.95, 95%CI: 1.17-3.23) in CD and (CCTTT)7 (P = 0.009; OR = 7.61, 95%CI: 1.25-46.08), (CCTTT)11 (P = 0.05; OR = 0.51, 95%CI: 0.25-1.01), (CCTTT)14 (P = 0.02; OR = 2.05, 95%CI: 1.07-3.94), (CCTTT)15 (P = 0.01; OR = 2.25, 95%CI: 1.16-4.35) repeats in UC patients indicated its possible association with higher disease risk which need to be confirmed in a larger sample size.

CONCLUSION

Our results suggest that the NOS2A_ (CCTTT)n gene variations may influence IBD susceptibility in the Moroccan population.

Keywords: HIF1A; NFKB1; NOS2A; Inflammatory bowel disease; Moroccan patients

Core tip: This is the first study to assess the involvement of oxidative pathway related genes in inflammatory bowel disease (IBD) development and to determine a possible effect of these variants on clinical course. We genotyped 507 subjects grouped in 308 healthy controls and 199 IBD patients for the (TAAA)n_rs12720460 and (CCTTT)n_rs3833912 NOS2A microsatellite repeats, HIF-1A_rs11549467 and NFKB1-94ins/delATTG_rs28362491 polymorphisms. The present study showed that NOS2A_ (CCTTT)n gene variations may influence IBD susceptibility in the Moroccan population. However, our data do not support a role for the NFKB1 and HIF1A polymorphisms in the pathogenesis of IBD.