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

<div><p>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 <i>RAD51</i>, <i>XRCC</i>3 and <i>hMSH2</i> 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 <i>hMSH</i>2 in the UC group caused statistically significant increased risk for UC compared to controls (OR 1.64, 95% CI 1.16–2.31, <i>p</i> = 0.004). Similarly, the CT genotype of <i>XRCC</i>3 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, <i>p</i> = 0.03), further confirming the risk of ‘T’ allele in UC. The GC genotype frequency of <i>RAD</i>51 gene was significantly increased (<i>p</i> = 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, <i>p</i> = 0.02) confirming the strong association of ‘C’ allele with UC. Among the controls, the SNP loci combination of <i>hMSH</i>2:<i>XRCC</i>3 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.</p></div

<i>hMSH</i>2 genotypic distribution in UC compared to healthy controls.

<p><i>hMSH</i>2 genotypic distribution in UC compared to healthy controls.</p

Haplotype association with response.

<p>Haplotype association with response.</p

<i>RAD</i>51 genotypic distribution in patients with UC compared to healthy controls.

<p><i>RAD</i>51 genotypic distribution in patients with UC compared to healthy controls.</p

Allele frequency distributions of <i>hMSH</i>2 <i>XRCC</i>3 <i>RAD</i>51 (G135C) in UC and healthy controls.

<p>Allele frequency distributions of <i>hMSH</i>2 <i>XRCC</i>3 <i>RAD</i>51 (G135C) in UC and healthy controls.</p

<i>XRCC</i>3 genotypic distribution in patients with UC and healthy controls.

<p><i>XRCC</i>3 genotypic distribution in patients with UC and healthy controls.</p

Pairwise Linkage Disequilibrium estimates in controls and Ulcerative colitis group.

<p>Pairwise Linkage Disequilibrium estimates in controls and Ulcerative colitis group.</p