Haplotype Analyses of DNA Repair Gene Polymorphisms and Their Role in Ulcerative Colitis

Abstract

Ulcerative colitis (UC) is a major clinical form of inflammatory bowel disease. UC is characterized by mucosal inflammation limited to the colon, always involving the rectum and a variable extent of the more proximal colon in a continuous manner. Genetic variations in DNA repair genes may influence the extent of repair functions, DNA damage, and thus the manifestations of UC. This study thus evaluated the role of polymorphisms of the genes involved in DNA repair mechanisms. A total of 171 patients and 213 controls were included. Genotyping was carried out by ARMS PCR and PCR-RFLP analyses for RAD51, XRCC3 and hMSH2 gene polymorphisms. Allelic and genotypic frequencies were computed in both control & patient groups and data was analyzed using appropriate statistical tests. The frequency of ‘A’ allele of hMSH2 in the UC group caused statistically significant increased risk for UC compared to controls (OR 1.64, 95% CI 1.16–2.31, p = 0.004). Similarly, the CT genotype of XRCC3 gene was predominant in the UC group and increased the risk for UC by 1.75 fold compared to controls (OR 1.75, 95% CI 1.15–2.67, p = 0.03), further confirming the risk of ‘T’ allele in UC. The GC genotype frequency of RAD51 gene was significantly increased (p = 0.02) in the UC group (50.3%) compared to controls (38%). The GC genotype significantly increased the risk for UC compared to GG genotype by 1.73 fold (OR 1.73, 95% CI 1.14–2.62, p = 0.02) confirming the strong association of ‘C’ allele with UC. Among the controls, the SNP loci combination of hMSH2:XRCC3 were in perfect linkage. The GTC and ACC haplotypes were found to be predominant in UC than controls with a 2.28 and 2.93 fold significant increase risk of UC.

Positive effect of single nucleotide RAD51 135G>C polymorphism and low Ku70 protein expression on female rectal cancer patients survival after preoperative radiotherapy

“…In the current study, CC genotype had the lowest frequency (2.9%), which is in agreement with other studies showing 1.5%-4.0% (13)(14)(15). However, GG genotypic frequency was found to be predominant (76.5%), being also in accordance with other studies showing 45.6%-86.5% (13)(14)(15). Tumors with GG genotype contained higher percentage of hypoxia and Ku70 expression than those with CC genotype, manifested the highest tumor aneuploidy, and developed the highest number of recurrences and metastases.…”

“…In our study, the mean incidence of GC genotype was 24.3%, which is in accordance with the results of other studies (13)(14)(15)18) showing 12%-50%, based on the analysis of normal cells from patients with cancer. Tumors had biological characteristics similar to those of GG homozygotes.…”

“…Tumors had biological characteristics similar to those of GG homozygotes. It was shown that in non-irradiated gut, the GC genotype significantly increases the risk of ulcerative colitis than GG genotype (15).…”

Haplotype analysis of BRCA1 intragenic markers in Iranian patients with familial breast and ovarian cancer

“…Founder mutation analysis performed using haplotype assessment to find the first carrier of mutation, in several population founder mutation have been originated ( 12 - 16 ). Genetic polymorphism of tumor suppressor and DNA repair genes have been involved in breast cancer risk ( 17 ).…”