Associations of NOD2 polymorphisms with Erysipelotrichaceae in stool of in healthy first degree relatives of Crohn's disease subjects.
BMC Med Genet
; 21(1): 204, 2020 10 15.
Article
en En
| MEDLINE
| ID: mdl-33059653
ABSTRACT
BACKGROUND:
Genetic analyses have identified many variants associated with the risk of inflammatory bowel disease (IBD) development. Among these variants, the ones located within the NOD2 gene have the highest odds ratio of all IBD genetic risk variants. Also, patients with Crohn's disease (CD) have been shown to have an altered gut microbiome, which might be a reflection of inflammation itself or an effect of other parameters that contribute to the risk of the disease. Since NOD2 is an intracellular pattern recognition receptor that senses bacterial peptidoglycan in the cytosol and stimulates the host immune response (Al Nabhani et al., PLoS Pathog 13e1006177, 2017), it is hypothesized that NOD2 variants represent perfect candidates for influencing host-microbiome interactions. We hypothesized that NOD2 risk variants affect the microbiome composition of healthy first degree relative (FDR) of CD patients and thus potentially contribute to an altered microbiome state before disease onset.METHODS:
Based on this, we studied a large cohort of 1546 healthy FDR of CD patients and performed a focused analysis of the association of three major CD SNPs in the coding region of the NOD2 gene, which are known to confer a 15-40-fold increased risk of developing CD in homozygous or compound heterozygous individuals.RESULTS:
Our results show that carriers of the C allele at rs2066845 was significantly associated with an increase in relative abundance in the fecal bacterial family Erysipelotrichaceae.CONCLUSIONS:
This result suggests that NOD2 polymorphisms contribute to fecal microbiome composition in asymptomatic individuals. Whether this modulation of the microbiome influences the future development of CD remains to be assessed.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Crohn
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Predisposición Genética a la Enfermedad
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Polimorfismo de Nucleótido Simple
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Proteína Adaptadora de Señalización NOD2
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Heces
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Firmicutes
Tipo de estudio:
Diagnostic_studies
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
BMC Med Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Canadá