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.
Halfvarson
J
J
Division of Gastroenterology, Department of Internal Medicine, Orebro University Hospital, 701 85 Orebro, Sweden. jonas.halfvarson@orebroll.se
Bresso
F
F
D'Amato
M
M
Järnerot
G
G
Pettersson
S
S
Tysk
C
C
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