Role of Genetic Factors in Inflammatory Bowel Disease

According to the remarks of gastroenterologists, prevalence of inflammatory bowel disease is increasing in our country. Since these diseases are the cause of multiple complications and low quality of life in patients, it mandates more considerations. On the other hand the pathogenesis of inflammatory bowel disease remained unclear and majority of researchers confirm the interaction of genetics, immunologic and environmental factors in its pathogenesis. Considering these factors separately is an important point in understanding the pathogenesis of the disease. This article evaluates the role of genetic factors in inflammatory bowel disease and different studies, in this field. Since discovery of the first inflammatory bowel disease related chromosomal locus in 1996, 10 related chromosomal loci have been recognized. The majority of studies have been performed on CARD15/NOD2 gene [IBD1 locus] and its polymorphisms. Since understanding of exact pathogenesis of inflammatory bowel disease is important in promoting newer and more effective therapeutic modalities, this goal would be accessible with extension of such clarifying studies

[ frequency of C3435T MDR1 gene polymorphism in Iranian patients with ulcerative colitis]

P-glycoprotein, the product of MDR1 [multi drug resistance] gene, is a trans membrane efflux pump, transferring drugs and toxins from intracellular to extracellular domains. It acts as a protective barrier to keep toxins out of the body by excreting them into the bile, urine and intestinal lumen. In the human gastrointestinal tract, P-glycoprotein is found in high concentrations on the epithelial cells of colon and small intestine. MDR1 gene polymorphism such as C3435T is associated with lower Pglycoprotein expression, thus it is suggested to have an association with ulcerative colitis. We tried to determine the frequency of C3435T polymorphism of MDR1 gene in Iranian patients with ulcerative colitis and compare it with healthy control population. In this case-control designed study, we assessed the C3435T polymorphism of MDR1 gene, in 150 ulcerative colitis patients and 150 sex- and ethnicity-matched healthy controls, who were visited at a teaching hospital during a one year period.[2002-2003]. The extracted leukocyte DNA was amplified by polymerase chain reaction [PCR] with specific primers, and C3435T polymorphism was detected by RFLP method. The mean age of patients was 40.1+/-13.9 years [14-74] and of controls was 40.7+/-14.0 years [16-79]. The frequency of C3435T allele was significantly higher in ulcerative colitis patients compared with controls [OR=1.58, 95% CI= 1.13 - 2.22, p<0.008]. The frequency of C/T genotype was also significantly higher in patients with ulcerative colitis [OR=1.67, 95% CI=1.06-2.64, p<0.028]. This study suggests that the higher frequency of 3435T allele has an association with ulcerative colitis in Iranian population as previously reported in western countries

frequency of three common mutations of CARD15/NOD2 gene in Iranian IBD patients

CARD15/NOD2 gene, located on the pericentromeric region of chromosome 16 [IBD1] has been reported to have an association with IBD, especially Crohn's disease [CD]. Many independent studies have shown a variable association between three common mutations of CARD 15, with Crohn's disease in different ethnic groups. Thus, raising the hypothesis that genetic and / or allelic heterogeneity may influence the relationship between CARD 15 and Crohn's disease. In the present study, we have investigated the frequency of three main mutations of CARD 15 gene [Arg 702 Trp, Gly 908 Arg and Leu 1007 fsinsC] in Iranian IBD patients and compared it with healthy control population. For this case-control study, 100 ulcerative colitis [UC], 40 Crohn's disease patients and 100 sex- age- and ethnicity-matched controls were enrolled from a teaching hospital during a one year period [2003-2004]. All three mutations were assessed on DNA of leukocyte cells, by PCR [Polymerase Chain Reaction] and RFLP [Restriction Fragment Length Polymorphism] methods. The mean age of UC, CD and healthy controls were 38.6 +/- 14.3, 36.6 +/- 14.1, and 38.6 +/- 14.2 years. Among the three evaluated CARD 15 gene mutations, the frequency of Arg702Trp mutation was significantly higher in Iranian patients with Crohn's disease [OR19.2; 95%CI:4.2-87.3, p<0.001]. None of these mutations were associated with ulcerative colitis. This study showed that Arg702Trp mutation of CARD 15 gene is probably associated with Crohn's disease in Iranian population; indicating that genetic polymorphisms may differ between populations