JOURNAL ARTICLE

CARD15/NOD2 polymorphisms do not explain concordance of Crohn's disease in Swedish monozygotic twins

J Halfvarson, F Bresso, M D'Amato, G Järnerot, S Pettersson, C Tysk
Digestive and Liver Disease 2005, 37 (10): 768-72
16002353

BACKGROUND: CARD15/NOD2 polymorphisms are associated with Crohn's disease. There is a high concordance for disease and disease phenotype in monozygotic twin pairs with Crohn's disease.

AIM: We studied CARD15/NOD2 polymorphisms in a Swedish, population-based cohort of monozygotic twins with Crohn's disease to assess whether these variants explain disease concordance.

SUBJECTS AND METHODS: Twenty-nine monozygotic twin pairs (concordant n=9, discordant n=20) with Crohn's disease and 192 healthy controls were investigated for the CARD15/NOD2 variants Arg702Trp, Gly908Arg and Leu1007fsinsC.

RESULTS: CARD15/NOD2 mutations were found in 5/38 (13%) twins with Crohn's disease, corresponding to a total allele frequency of 6.6%. Only 2/9 concordant twin pairs carried any of the variants and the remaining seven were wild type genotype. The total allele frequency was 4.4 times higher (95% confidence interval 1.0-21.5, p=0.06) in concordant twins than in discordant ones, 11.1% versus 2.5%. In healthy controls the total allele frequency was 2.6%.

CONCLUSIONS: CARD15/NOD2 polymorphisms contribute but do not alone explain concordance of Crohn's disease in monozygotic twins and, at least in a Swedish population, other polymorphisms are required. The low occurrence of CARD15/NOD2 mutations in the study and other Northern European populations suggests that these variants are of less importance in Northern Europe.

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