NOD2/CARD15 in healthy relatives of IBD patients

V. Annese, A. Latiano, O. Palmieri, G. Lombardi, A. Andriulli

On behalf of Italian Group of Inflammatory Bowel Disease (IG-IBD) U.O. Gastroenterologia, Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG (Italy)

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• Gastroenterology

Background: Crohn’s disease (CD) and Ulcerative Colitis (UC) are related chronic inflammatory disorders of the intestine (IBD) caused by a combination of genetic and environmental factors. Three polymorphisms within the NOD2/CARD15 gene are highly associated with CD, increasing the risk from 2 up to 44-fold, depending on the presence of one or two risk alleles.
Aim of this study was to investigate the presence of two risk alleles on healthy relatives of IBD patients and prospectively follow them for possible development of IBD.

Materials and Methods: Healthy relatives of familial IBD patients were recruited in our Institution and across Italy in a multicenter study of the IG-IBD. One hundred and twenty one IBD families were identified and blood samples were obtained from 415 first-degree healthy relatives. Single nucleotide polymorphisms (SNPs) R702W, G908R, and L1007finsC of the CARD15 gene were investigated by multiplex pyrosequencing technique. Data obtained in 205 healthy controls (HC) were compared by chi-square or Fisher’s test.

Results: Ninety eight (28.7%) healthy relatives had one risk allele (HC 14.6%; p = 0.002, OR 2, C.I. 1-4), while 8 had two risk alleles (vs 0.5% of healthy controls; p = 0.01). All subjects were asymptomatic at the time of blood sample and record collections (between 1996 and 1999) and were further investigated with abdominal ultrasonography, blood chemistry and haemoccult test, after 5-8 years of follow-up. All were still asymptomatic with negative findings.

Conclusions: Our study once again supports the importance of gene-gene and gene-environment interactions for the final development of the disease.