Influence of the inducible nitric oxide synthase gene (NOS2A) on inflammatory bowel disease susceptibility.
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.
Martín
M Carmen
MC
Servicio de Inmunología Clínica, Hospital Clínico San Carlos, 1a planta Sur, c/ Profesor Martín Lagos s/n, 28040 Madrid, Spain. cmartal@terra.es
Martinez
Alfonso
A
Mendoza
J Luis
JL
Taxonera
Carlos
C
Díaz-Rubio
Manuel
M
Fernández-Arquero
Miguel
M
de la Concha
Emilio G
EG
Urcelay
Elena
E
D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000201:enzymology / Q000235:genetics; D003424:Crohn Disease / Q000201:enzymology / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013030:Spain
D017931:DNA Primers; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II