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


OBJECTIVE
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.


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.
Division of Gastroenterology, Department of Internal Medicine, Orebro University Hospital, 701 85 Orebro, Sweden. jonas.halfvarson@orebroll.se
J
J
Halfvarson
F
F
Bresso
M
M
D'Amato
G
G
Järnerot
S
S
Pettersson
C
C
Tysk
D000293:Adolescent; D000328:Adult; D001120:Arginine; D016022:Case-Control Studies; D002648:Child; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005998:Glycine; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007930:Leucine; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein; D011110:Polymorphism, Genetic; D013548:Sweden / Q000453:epidemiology; D014364:Tryptophan; D014430:Twins, Monozygotic / Q000235:genetics*
D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D014364:Tryptophan; D001120:Arginine; D007930:Leucine; D005998:Glycine