ABSTRACT
Inflammatory bowel disease [IBD] is a chronic disease of unknown etiology, in which genetic factors, seem to play an important role in the disease predisposition and course. Assessment of tumor necrosis factor [TNF- alpha] gene polymorphisms in many populations showed a possible association with IBD. Considering the genetic variety in different ethnic groups, the aim of the present study was to investigate the association of five important single nucleotide polymorphisms [SNPs] in the promoter region of [TNF- alpha] gene with IBD in Iran. In this case-control study, 156 Ulcerative colitis [UC] patients, 50 Crohn's disease [CD] patients and 200 sex and age matched healthy controls of Iranian origin were enrolled. The study was performed during a two year period [2008-2010] at Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. DNA samples were evaluated for [TNF- alpha] gene polymorphisms [including -1031, -863, -857, -308 and -238] by PCR and RFLP methods. The frequency of the mutant allele of -1031 polymorphism was significantly higher in Iranian patients with Crohn's disease compared to healthy controls [P=0.01, OR=1.92; 95% CI: 1.14-3.23]. None of the other evaluated polymorphisms demonstrated a significant higher frequency of mutant alleles in Iranian IBD patients compared to controls. Among the five assessed [SNPs], only -1031 polymorphism of [TNF- alpha] gene may play a role in disease susceptibility for Crohn's disease in Iran. This pattern of distribution of [TNF- alpha] gene polymorphisms could be specific in this population
ABSTRACT
Sporadic colorectal cancer is the fourth most common cancer in Iran. The DNA repair protein O6- methylguanine-DNA methyltransferase [MGMT] is involved in the cellular defense against alkylating agents. Genetic alterations in the MGMT gene may impair the protein's ability to remove alkyl groups from the O6-position of guanine, thereby raising the mutation rate and increasing the risk of sporadic colorectal cancer. We hypothesized that amino acid substitution polymorphisms in the MGMT gene may be associated with the genetic susceptibility to sporadic colorectal cancer. We assessed five non-synomymous polymorphisms [Pro58Ser, Leu84Phe, Arg128Gln, Ile143Val, Gly160Arg] in the MGMT gene by PCR/Pyrosequencing. The population studied consisted of 200 sporadic colorectal cancer patients and 200 healthy individuals [blood donors], all of Iranian origin. Allele frequencies and genotypes were compared between the two groups. Odds ratios were calculated and the interactions among the polymorphisms, age and sex were examined. There was a significant association between two amino acid substitution polymorphisms [Arg128Gln and Gly160Arg] of MGMT gene and sporadic colorectal cancer. We could show a significant association between the two polymorphisms and colorectal cancer. This might be a superior marker for colon cancer screening in the future