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CARD15 mutations in patients with Crohn's disease in a homogeneous Spanish population
Concepción Núñez1, Manuel Barreiro, J Enrique Domínguez-Muñoz
1Laboratory of Immunogenetics and Department of Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands.
Insights
CARD15 gene mutations G908R and 1007fs are linked to Crohn's disease susceptibility in Galicia, Spain. Frequencies of these mutations are lower in this population compared to other Caucasian groups.
Area of Science:
- Genetics
- Gastroenterology
- Immunology
Background:
- Three CARD15 mutations are consistently linked to Crohn's disease (CD) susceptibility, primarily in Caucasian populations.
- Previous studies have shown inconsistent replication of these findings across diverse populations.
- The role of CARD15 mutations in CD susceptibility requires further investigation in homogeneous populations.
Purpose of the Study:
- To investigate the association of CARD15 mutations with Crohn's disease in a homogeneous population from Northwest Spain (Galicia).
- To analyze the influence of CARD15 variants on overall CD susceptibility and clinical subphenotypes.
Main Methods:
- Genotyping of 165 CD patients and 165 healthy controls from Galicia for CARD15 variants (R702W, G908R, 1007fs).
- Association analyses were conducted to determine the relationship between CARD15 mutations and CD.
- Stratification analysis was performed to assess the impact on clinical subphenotypes and disease behavior.
Main Results:
- Allele frequencies of CARD15 variants were lower in the Galician population compared to other European cohorts.
- G908R and 1007fs variants showed significant association with overall Crohn's disease susceptibility.
- Associations with overall susceptibility were not maintained in clinical subgroups due to limited sample size; however, G908R and 1007fs were linked to disease duration influencing disease behavior.
Conclusions:
- CARD15 variants G908R and 1007fs are associated with Crohn's disease susceptibility in the Galician population.
- The R702W variant did not show a significant association.
- The observed lower frequency of these mutations in Galicia warrants further population-specific genetic studies.
Objectives:
Three mutations in CARD15 have been repeatedly shown to be involved in Crohn's disease susceptibility, mainly in Caucasian individuals. However, those findings were not replicated in all populations studied so far. In this work, we studied the role of CARD15 mutations in a relatively homogeneous population from the Northwest of Spain, Galicia.
Methods:
One hundred and sixty-five patients with Crohn's disease and a similar number of healthy controls were recruited from a single center in Galicia. All individuals were genotyped for the three main Crohn's disease associated CARD15 variants (R702W, G908R, and 1007fs). Association analyses were performed to study the influence of those mutations on Crohn's disease overall and on clinical subphenotypes.
Results:
The allele frequencies of CARD15 variants were lower in this population than in most of the European populations studied so far. G908R and 1007fs were significantly associated with overall susceptibility to Crohn's disease. However, these associations were lost after stratification to clinical subgroups, probably due to the small number of cases in these subgroups. Significant associations were found between G908R and 1007fs and the behavior of Crohn's disease, but they were due to the influence of years of disease on the behavior of the disease rather than being the result of a direct effect of these mutations on disease behavior.
Conclusions:
The CARD15 variants G908R and 1007fs, but not R702W, are associated with susceptibility to Crohn's disease in Galicia. Interestingly, the frequency of these mutations appears to be lower than in other Caucasian populations studied so far.
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