Association of genetic variation in the NR1H4 gene, encoding the nuclear bile acid receptor FXR, with inflammatory bowel disease.
BMC Res Notes
; 5: 461, 2012 Aug 28.
Article
em En
| MEDLINE
| ID: mdl-22929053
ABSTRACT
BACKGROUND:
Pathogenesis of inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), involves interaction between environmental factors and inappropriate immune responses in the intestine of genetically predisposed individuals. Bile acids and their nuclear receptor, FXR, regulate inflammatory responses and barrier function in the intestinal tract.METHODS:
We studied the association of five variants (rs3863377, rs7138843, rs56163822, rs35724, rs10860603) of the NR1H4 gene encoding FXR with IBD. 1138 individuals (591 non-IBD, 203 UC, 344 CD) were genotyped for five NR1H4 genetic variants with TaqMan SNP Genotyping Assays.RESULTS:
We observed that the NR1H4 SNP rs3863377 is significantly less frequent in IBD cases than in non-IBD controls (allele frequencies P = 0.004; wild-type vs. SNP carrier genotype frequencies P = 0.008), whereas the variant rs56163822 is less prevalent in non-IBD controls (allele frequencies P = 0.027; wild-type vs. SNP carrier genotype frequencies P = 0.035). The global haplotype distribution between IBD and control patients was significantly different (P = 0.003). This also held true for the comparison between non-IBD and UC groups (P = 0.004), but not for the comparison between non-IBD and CD groups (P = 0.079).CONCLUSIONS:
We show that genetic variation in FXR is associated with IBD, further emphasizing the link between bile acid signaling and intestinal inflammation.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Doenças Inflamatórias Intestinais
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Receptores Citoplasmáticos e Nucleares
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Predisposição Genética para Doença
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Polimorfismo de Nucleotídeo Único
Tipo de estudo:
Etiology_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article