Influence of the inducible nitric oxide synthase gene (<Emphasis Type="Italic">NOS2A</Emphasis>) on inflammatory bowel disease susceptibility |
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Authors: | M Carmen Martín Alfonso Martinez J Luis Mendoza Carlos Taxonera Manuel Díaz-Rubio Miguel Fernández-Arquero Emilio G de la Concha Elena Urcelay |
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Institution: | (1) Servicio de Inmunología Clínica, Hospital Clínico San Carlos, 1a planta Sur, c/ Profesor Martín Lagos s/n, 28040 Madrid, Spain;(2) Department of Gastroenterology, Hospital Clínico San Carlos, Madrid, Spain |
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Abstract: | The great amount of nitric oxide (NO) produced by the inducible isoform of NO synthase (iNOS) exerts deleterious effects,
and iNOS expression is raised in the colonic mucosa of inflammatory bowel disease (IBD) patients. This is the first association
analysis of polymorphisms within the NOS2A extended gene with IBD susceptibility. We analyzed 336 patients of Crohn’s disease (CD), 355 of ulcerative colitis (UC),
and 536 healthy controls from a Spanish population. We tested a (CCTTT)n microsatellite, a (−/TAAA) insertion, and two single
nucleotide polymorphisms (SNPs) flanking them (rs2779251 and rs2779248) in the NOS2A promoter, together with two SNPs in the coding region: one within exon 10, D385D (rs1137933), and another mapping to exon
16, S608L (rs2297518). Analysis of these markers evidenced differences among IBD patients and healthy controls. Allele (CCTTT)
13 is related to higher UC risk (p = 0.001; odds ratio OR] 95% confidence interval, CI] = 1.64 1.20–2.23]). Carriers of minor alleles of the two promoter
SNPs analyzed showed an association with UC predisposition, and common allele homozygotes of the two exonic SNPs were more
frequent among CD patients than among controls. Concordantly, one out of the three haplotypes carrying both exonic risk alleles
was found to increase CD susceptibility (p = 0.007; OR 95%CI] = 1.74 1.13–2.67]). Therefore, the NOS2A gene seems to be involved in IBD aetiology. |
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Keywords: | Nitric oxide synthase (NOS) Inflammatory bowel diseases (IBD) Genetic susceptibility |
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