Dopamine D2 receptor polymorphisms in inflammatory bowel disease and the refractory response to treatment

Dopamine and its receptors may be involved in inflammatory reaction. The availability of this molecule depends on its receptors. The DRD2 gene, which codifies for the D2 dopamine receptor, has several polymorphisms. In this study, the DRD2 TaqIA polymorphism, which confers a decreased receptor density, was evaluated in 313 individuals including 220 inflammatory bowel disease patients (143 patients with Crohn's disease and 77 with ulcerative colitis) and in 93 healthy blood donors. The analysis was carried out by PCR-RFLP techniques. The frequencies of A (1) A (1) and A (2) A (2) genotypes were similar among Crohn's disease, ulcerative colitis patients, and health controls. Also, the genotype frequency was similar in different groups of disease localization, behavior, and age of disease onset. However, the Crohn's disease patients carriers of A (2) A (2) genotype showed a lower risk for development refractory Crohn's disease (37 out 65) than A (1) A (1) and A (1) A (2) carriers (28 out of 65) [(OR=0.4, 95% CI 0.21-0.87; p=0.02)]. Our results support an involvement of the dopamine receptor in inflammatory bowel disease and suggest a new potential target for therapy in refractory Crohn's disease patients.