Dataset Information

DNA Repair Gene (XRCC1) Polymorphism (Arg399Gln) Associated with Schizophrenia in South Indian Population: A Genotypic and Molecular Dynamics Study.

ABSTRACT: This paper depicts the first report from an Indian population on the association between the variant Arg399Gln of XRCC1 locus in the DNA repair system and schizophrenia, the debilitating disease that affects 1% of the world population. Genotypic analysis of a total of 523 subjects (260 patients and 263 controls) revealed an overwhelming presence of Gln399Gln in the case subjects against the controls (P < 0.0068), indicating significant level of association of this nsSNP with schizophrenia; the Gln399 allele frequency was also perceptibly more in cases than in controls (p < 0.003; OR = 1.448). The results of the genotypic studies were further validated using pathogenicity and stability prediction analysis employing computational tools [I-Mutant Suite, iStable, PolyPhen2, SNAP, and PROVEAN], with a view toassess the magnitude of deleteriousness of the mutation. The pathogenicity analysis reveals that the nsSNP could be deleterious inasmuch as it could affect the functionality of the gene, and interfere with protein function. Molecular dynamics simulation of 60ns was performed using GROMACS to analyse structural change due to a mutation (Arg399Gln) that was never examined before. RMSD, RMSF, hydrogen bonds, radius of gyration and SASA analysis showedthe existence of asignificant difference between the native and the mutant protein. The present study gives astrong indication that the XRCC1 locus deserves serious attention, as it could be a potential candidatecontributing to the etio-pathogenesis of the disease.

SUBMITTER: Sujitha SP

PROVIDER: S-EPMC4732819 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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DNA Repair Gene (XRCC1) Polymorphism (Arg399Gln) Associated with Schizophrenia in South Indian Population: A Genotypic and Molecular Dynamics Study.

Sujitha S P SP Kumar D Thirumal DT Doss C George Priya CG Aavula K K Ramesh R R Lakshmanan S S Gunasekaran S S Anilkumar G G

PloS one 20160129 1

This paper depicts the first report from an Indian population on the association between the variant Arg399Gln of XRCC1 locus in the DNA repair system and schizophrenia, the debilitating disease that affects 1% of the world population. Genotypic analysis of a total of 523 subjects (260 patients and 263 controls) revealed an overwhelming presence of Gln399Gln in the case subjects against the controls (P < 0.0068), indicating significant level of association of this nsSNP with schizophrenia; the G ...[more]

PMID: 26824244

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Project description:Background: Several environmental and genetic factors have contributed to the development of colorectal cancer (CRC). We aimed to investigate the independent and combined effects of some selected risk factors and Arg399Gln XRCC1 polymorphism on CRC. Methods: A total of 180 patients with CRC and 160 healthy individuals who were matched for sex, age, and place of residence (Northeast of Iran) participated in this case-control study. Before collecting blood samples and filling out questionnaires, a written consent form was obtained from all participants. Genotypes were determined by RFLP-PCR. The comparison of genotype and allele frequencies was performed using p value based on the results of chi-square test. The odds ratios (OR) and 95% confidence intervals (CI) were calculated by employing a logistic regression model. All statistical calculations were performed using SPSS. Each of the 2- sided p values less than 0.05 were considered statistically significant. Results: The level of literacy, physical activity, consumption of vegetables and fruits, and tea intake of the patients were significantly lower than healthy individuals, but gastrointestinal disorders, family history of cancer, BMI, and fast food consumption were significantly higher in cases than in controls. No significant difference was observed between the 2 groups regarding smoking, opioid addiction, alcohol consumption, diet, fish consumption, and liquid intake, using the kitchen hood, diabetes, and cardiovascular disease. Arg/Gln + Gln/Gln and Arg/Gln genotypes were involved in increased CRC risk (The crude OR =1.781 with a 95% CI of 1.156-2.744 and OR = 1.690 with a 95% CI of 0.787-3.630). Also, Gln/Gln genotype was more frequent in CRC group than in control group. However, none of the risk factors interacted with polymorphism, and thus did not have an effect on CRC. Conclusion: Some risk factors, such as reducing the consumption of vegetables and fruits or reducing physical activity as well as polymorphism of the XRCC1 Arg399Gln alone, increase the risk of CRC, but they do not interact with each other.

Project description:BackgroundSmoking has been considered to be the major cause of lung cancer. However, only a fraction of cigarette smokers develop this disease. This suggests the importance of genetic constitution in predicting the individual's susceptibility towards lung cancer. This genetic susceptibility may result from inherited polymorphisms in genes controlling carcinogen metabolism and repair of damaged deoxyribonucleic acid (DNA). These repair systems are fundamental to the maintenance of genomic integrity. X-ray repair cross complimenting group I (XRCC1), a major DNA repair gene in the base excision repair (BER) pathway. It is involved in repair by interacting with components of DNA at the site of damage. Inconsistent results have been reported regarding the associations between the Arg399Gln polymorphism of XRCC1. This study demonstrates the importance of recognition of this relationship of lung carcinoma and genetic constitution of the person which will help guide clinicians on the optimal screening of this disease.AimTo assess the role of XRCC1 gene polymorphism (Arg399Gln) directly on the variation in susceptibility to development of lung cancer in North Indian subjects.Materials and methodsOne hundred males with diagnosed cases of lung cancer were recruited from Delhi State Cancer Institute (DSCI). Hundred healthy volunteers were taken as controls. DNA isolation was done and Polymerase chain reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) procedure undertaken to amplify the region containing Arg/Gln substitution at codon 399 (in exon 10).ResultsXRCC1 gene polymorphism is associated with increased risk of lung cancer when the Arg/Arg genotype was used as the reference group. The Arg/Gln and Gln/Gln was associated with statistically increased risk for cancer.ConclusionArg399Gln polymorphism in XRCC1 gene polymorphism is associated with lung cancer in North Indian subjects and screening for this polymorphism will help in targeting predisposed individuals and its prevention.

Dataset Information

DNA Repair Gene (XRCC1) Polymorphism (Arg399Gln) Associated with Schizophrenia in South Indian Population: A Genotypic and Molecular Dynamics Study.

Publications

DNA Repair Gene (XRCC1) Polymorphism (Arg399Gln) Associated with Schizophrenia in South Indian Population: A Genotypic and Molecular Dynamics Study.

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