NOD2c.3019-3020insC AND c.2104C>T GENE VARIANTS AMONG PATIENTS FROM WESTERN UKRAINE WITH CROHN'S DISEASE AND COLORECTAL CANCER.

Abstract

To determine the frequency of NOD2gene c.3019-3020insC (rs5743293) and c.2104C>T (rs2066844) allelic variants in thepatients with Crohn's disease (CD), colorectal cancer (CRC) and in the control groups and to study the association of these mutations with the onset time of the diseases, gender and surgical interventions. The diagnoses of CD and CRC were established based on standard clinical examination and laboratory tests. Molecular genetic study of a frameshift 3020insC mutations of NOD2gene were performed in 54patients with CD; missense R702W mutations of the NOD2gene- in 41CD patients and 38healthy controls. In CRC group, 3020insC mutation was tested in 48patients, R702W mutation- in 40patients and 40healthy controls. PCR-RFLP technique was used to identify the mutations. The frequency of the minor allele (M) of 3020insC mutation of NOD2gene in the patients with CD was significantly higher than in the control group (р = 0.01). The age at CD onset in females carrying 3020insC mutation was significantly lower (22.5 ± 1.6years) when compared with females without the mutation (32.7 ± 2.5years) (p = 0.002). There was no significant difference in the allele frequencies and genotype distributions of R702W mutation in the patients with CD in comparison with the controls. The mean age at CD onset in the patients carrying R702W mutation was significantly lower (28.4 ± 1.4years) compared with the patients without the mutation (39.4 ± 2.8years) (p<0.01). Surgical interventions for CD was required in 40.0% of 3020insC mutation carriers. Among patients with CRC, only4.2% carried 3020insC mutation and 20.0% R702W mutation. Our study suggests that R702W and 3020insC mutations are not associated with the risk of CRC in Ukrainian patients. There was no statistically significant difference in mean age at CRC onset in patients with/without R702W mutation. Only one patient with CRC had two mutations. The earlier age at CD onset was associated with 3020insC mutation, but only in female patients. The association between R702W mutation and the earlier age of CD onset was found. Patients with 3020insC mutation showed a trend to a higher frequency of surgical interventions for CD.