alexa Polymorphism in the DNA repair enzyme XRCC1: utility of current database and implications for human health risk assessment.
Infectious Diseases

Infectious Diseases

Journal of Meningitis

Author(s): Ginsberg G, Angle K, Guyton K, Sonawane B

Abstract Share this page

Abstract Genetic polymorphisms are increasingly recognized as sources of variability not only in toxicokinetic but also in toxicodynamic response to environmental agents. XRCC1 is involved in base excision repair (BER) of DNA; it has variant genotypes that are associated with modified repair function. This analysis focuses on four polymorphisms: three in the coding region that affect protein structure and one in an upstream regulatory sequence that affects gene expression. The Arg399Gln variant is the most widely studied with evidence supporting a quantitative effect of genotype on phenotype. The homozygous variant (Gln/Gln) can have 3-4-fold diminished capacity to remove DNA adducts and oxidized DNA damage. This variant is relatively common in Caucasians and Asians where approximately 10\% are homozygous variant. In contrast, the Arg194Trp variant appears to protect against genotoxic effects although the degree to which DNA repair is enhanced by this polymorphism is uncertain. The homozygous variant is rare in Caucasians and African Americans but it is present at 7\% in Asians. A third coding region polymorphism at codon 280 appears to decrease repair function but additional quantitative information is needed and the homozygous variant is rare across populations studied. A polymorphism in an upstream promoter binding sequence (-77T>C) appears to lower XRCC1 levels by decreasing gene expression. Based upon genotype effect on phenotype and allele frequency, the current analysis finds that the codon 399 and upstream (-77) polymorphisms have the greatest potential to affect the toxicodynamic response to DNA damaging agents. However, the implications for risk assessment are limited by the likelihood that polymorphisms in multiple BER genes interact to modulate DNA repair. Copyright © 2011 Elsevier B.V. All rights reserved. This article was published in Mutat Res and referenced in Journal of Meningitis

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords