title: 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.
authors.affiliation: Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, Andhra Pradesh, India.
authors.forename: Avinash
authors.initials: A
authors.lastname: Bardia
authors.affiliation: Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, Andhra Pradesh, India.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Tiwari
authors.affiliation: Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, Andhra Pradesh, India.
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Vishwakarma
authors.affiliation: Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, Andhra Pradesh, India.
authors.forename: Md Aejaz
authors.initials: MA
authors.lastname: Habeeb
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, Andhra Pradesh, India.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Nallari
authors.affiliation: College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Shaik A
authors.initials: SA
authors.lastname: Sultana
authors.affiliation: College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Shaik A
authors.initials: SA
authors.lastname: Pasha
authors.affiliation: Neurobiology lab, Department of Zoology, University College of Sciences, Osmania University, Hyderabad, Andhra Pradesh, India.
authors.forename: Yugandhar P
authors.initials: YP
authors.lastname: Reddy
authors.affiliation: Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, Andhra Pradesh, India.
authors.forename: Aleem A
authors.initials: AA
authors.lastname: Khan
mesh_terms: D000483:Alleles; D003093:Colitis, Ulcerative / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D051718:MutS Homolog 2 Protein / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D051135:Rad51 Recombinase / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C110901:X-ray repair cross complementing protein 3; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein