CARD15 single nucleotide polymorphisms 8, 12 and 13 are not increased in ethnic Danes with sarcoidosis
Nils Milman1, Ole Haagen Nielsen, Thomas Vauvert F Hviid
1Department of Medicine B, Division of Lung Transplantation, Rigshospitalet, Copenhagen University Hospital, Institute of Medical Biochemistry and Genetics, University of Copenhagen, Copenhagen, Denmark. milman@rh.dk
Insights
Genetic analysis revealed no increased frequency of caspase-activating recruitment domain 15 (CARD15) mutations in Danish sarcoidosis patients compared to controls. These CARD15 mutations do not appear to influence the disease course in sarcoidosis.
Area of Science:
- Genetics
- Immunology
- Gastroenterology
Background:
- Mutations in the caspase-activating recruitment domain 15 (CARD15) gene are linked to Crohn's disease.
- Sarcoidosis, a granulomatous disease of unknown cause, shares histological similarities with Crohn's disease.
Purpose of the Study:
- To investigate the frequency of CARD15 mutations in ethnic Danish sarcoidosis patients.
- To compare CARD15 mutation frequencies in sarcoidosis patients with those in healthy controls.
Main Methods:
- Genotyping for specific CARD15 mutations (R702W, G908R, L1007fsinsC) using capillary electrophoresis.
- Analysis of 53 patients with histologically verified sarcoidosis and 103 healthy controls.
Main Results:
- No statistically significant difference in CARD15 mutation frequencies was observed between sarcoidosis patients (7.6%) and controls (7.3%).
- All identified mutations in both groups were heterozygous.
- CARD15 mutations did not significantly affect the disease course in sarcoidosis patients.
Conclusions:
- The frequency of CARD15 mutations is not elevated in Danish sarcoidosis patients.
- Heterozygosity for CARD15 mutations does not appear to influence the clinical course of sarcoidosis.
Background:
Mutations of the caspase-activating recruitment domain 15 (CARD15) gene on chromosome 16 are associated with chronic inflammatory granulomatous bowel disease (Crohn's disease). Sarcoidosis is a systemic granulomatous disease with unknown etiology, which shares histological features with Crohn's disease.
Objectives:
To evaluate whether ethnic Danes with sarcoidosis have an increased frequency of CARD15 mutations compared to healthy control subjects.
Methods:
Genotyping for CARD15 mutations R702W, G908R, and L1007fsinsC, also designated single nucleotide polymorphism (SNP) SNP8, SNP12 and SNP13, respectively, were performed by capillary electrophoresis single-strand confirmation polymorphism in 53 patients with histologically verified sarcoidosis and in 103 healthy controls.
Results:
The frequencies of CARD15 mutations in sarcoidosis patients were: SNP8, 4/106 chromosomes (3.8%); SNP12, 2/106 chromosomes (1.9%); SNP13, 2/106 chromosomes (1.9%); SNP8+SNP12+SNP13, 8/106 chromosomes (7.6%). All 8 patients were heterozygous. The frequencies in controls were: SNP8, 9/206 chromosomes (4.4%); SNP12, 2/206 chromosomes (1.0%); SNP13, 4/206 chromosomes (1.9%); SNP8+SNP12+SNP13, 15/206 chromosomes (7.3%). All controls were heterozygous. The differences were not statistically significant (p>0.05). Furthermore, the course of disease was not significantly different in the 8 patients with CARD15 mutations and the 45 patients without mutations.
Conclusion:
The frequency of CARD15 mutations is not increased in ethnic Danish patients with sarcoidosis, and heterozygosity for such mutations apparently has no influence on the course of disease.
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