CARD15 gene polymorphisms in Serbian patients with Crohn's disease: genotype-phenotype analysis.
OBJECTIVE
Genetic heterogeneity and incomplete phenotype penetrance complicate genetic analysis of Crohn's disease (CD). Studies in western Europe have shown that CARD15 polymorphisms increase susceptibility to CD, but frequencies vary within different European populations. The aim here was to evaluate the prevalence of CARD15 mutations and their phenotypic correlation in a Serbian population.


METHODS
131 patients with CD, 65 patients with ulcerative colitis, and 88 healthy controls were genotyped for three common mutations (R702W, G908R, Leu1007insC) by PCR-restriction fragment length polymorphism. chi and Student's t-test were used for statistical assessment.


RESULTS
At least one CARD15 disease-associated allele was found in 35.11% patients with CD, 14.77% of healthy controls (P=0.001), and 7.69% patients with ulcerative colitis (P=0.0001). The L1007fs mutation showed a significant association with CD (P<0.0001). The frequency of R702W mutant allele was almost equal in the control group and CD patients Univariate analyses established that CARD15 carriers had a significantly higher risk of isolated ileal location [P=0.042; odds ratio (OR) 2.30; 95% confidence interval (CI): 1.02-5.19], fibrostenotic behavior (P<0.0001; OR 9.86; 95% CI: 4.29-22.62), surgical resection (P=0.036; OR 2.2; CI, 1.046-4.626), and earlier onset of disease (P=0.026).


CONCLUSIONS
This study confirms that CARD15 carriers, especially L1007fs mutants, in central Europeans have an increased risk of CD and it is associated with earlier onset, ileal, fibrostenotic disease and a higher risk of surgery. Any influence of latitude is not matched by an east-west divide on the genotype frequency and phenotype of CD within Europe.
Protic
Marijana B
MB
Center for Gastroenterology and Hepatology, University Clinical Center, Zvezdara, Belgrade, Serbia. marijanaprotic@beotel.yu
Pavlovic
Sonja T
ST
Bojic
Daniela Z
DZ
Krstic
Miodrag N
MN
Radojicic
Zoran A
ZA
Tarabar
Dino K
DK
Stevanovic
Ana Z
AZ
Karan Djurasevic
Teodora Z
TZ
Godjevac
Mina V
MV
Svorcan
Petar V
PV
Dapcevic
Branka D
BD
Jojic
Njegica Z
NZ
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D044465:White People / Q000235:genetics
C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein