Multidrug resistance 1 gene polymorphisms may determine Crohn's disease behavior in patients from Rio de Janeiro.
OBJECTIVE
Conflicting data from studies on the potential role of multidrug resistance 1 gene polymorphisms in inflammatory bowel disease may result from the analysis of genetically and geographically distinct populations. Here, we investigated whether multidrug resistance 1 gene polymorphisms are associated with inflammatory bowel diseases in patients from Rio de Janeiro.


METHODS
We analyzed 123 Crohn's disease patients and 83 ulcerative colitis patients to determine the presence of the multidrug resistance 1 gene polymorphisms C1236T, G2677T and C3435T. In particular, the genotype frequencies of Crohn's disease and ulcerative colitis patients were analyzed. Genotype-phenotype associations with major clinical characteristics were established, and estimated risks were calculated for the mutations.


RESULTS
No significant difference was observed in the genotype frequencies of the multidrug resistance 1 G2677T/A and C3435T polymorphisms between Crohn's disease and ulcerative colitis patients. In contrast, the C1236T polymorphism was significantly more common in Crohn's disease than in ulcerative colitis (p = 0.047). A significant association was also found between the multidrug resistance 1 C3435T polymorphism and the stricturing form of Crohn's disease (OR: 4.13; p = 0.009), whereas no association was found with penetrating behavior (OR: 0.33; p = 0.094). In Crohn's disease, a positive association was also found between the C3435T polymorphism and corticosteroid resistance/refractoriness (OR: 4.14; p = 0.010). However, no significant association was found between multidrug resistance 1 gene polymorphisms and UC subphenotypic categories.


CONCLUSIONS
The multidrug resistance 1 gene polymorphism C3435T is associated with the stricturing phenotype and an inappropriate response to therapy in Crohn's disease. This association with Crohn's disease may support additional pathogenic roles for the multidrug resistance 1 gene in regulating gut-microbiota interactions and in mediating fibrosis. Understanding the effects of several drugs associated with multidrug resistance 1 gene variants may aid in the selection of customized therapeutic regimens.
Disciplina de Gastroenterologia e Endoscopia Digestiva, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brazil.
Ana Teresa P
AT
Carvalho
Disciplina de Gastroenterologia e Endoscopia Digestiva, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brazil.
Renata S B
RS
Fróes
Disciplina de Gastroenterologia e Endoscopia Digestiva, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brazil.
Barbara C
BC
Esberard
Instituto Nacional de Câncer, Programa de Carcinogênese Molecular, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brazil.
Juliana C V C
JC
Santos
Instituto Nacional de Câncer, Programa de Carcinogênese Molecular, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brazil.
Davy C M
DC
Rapozo
Disciplina de Gastroenterologia e Endoscopia Digestiva, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brazil.
Ana B
AB
Grinman
Laboratório de Toxicologia e Biologia Molecular, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brazil.
Tatiana A
TA
Simão
Laboratório de Toxicologia e Biologia Molecular, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brazil.
Pedro
P
Nicolau Neto
Instituto de Epidemiologia e Saúde Coletiva, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
Ronir R
RR
Luiz
Departamento de Clínica Médica, Serviço de Gastroenterologia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
Antonio José V
AJ
Carneiro
Departamento de Clínica Médica, Serviço de Gastroenterologia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
Heitor S P de
HS
Souza
Laboratório de Toxicologia e Biologia Molecular, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brazil.
Luis Felipe
LF
Ribeiro-Pinto
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D019450:Genes, MDR / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult