Effect of the thymine-DNA glycosylase rs4135050 variant on Saudi smoker population.


Journal

Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758

Informations de publication

Date de publication:
04 2019
Historique:
received: 27 07 2018
revised: 13 12 2018
accepted: 02 01 2019
pubmed: 20 2 2019
medline: 22 5 2019
entrez: 20 2 2019
Statut: ppublish

Résumé

Thymine-DNA glycosylase (TDG) is an essential DNA-repair enzyme which works in both epigenetic regulation and genome maintenance. It is also responsible for efficient correction of multiple endogenous DNA lesions which occur commonly in mammalian genomes. Research of genetic variants such as SNPs, resulting in disease, is predicted to yield clinical advancements through the identification of sensitive genetic markers and the development of disease prevention and therapy. To that end, the main objective of the present study is to identify the possible interactions between cigarette smoking and the rs4135050 variant of the TDG gene, situated in the intron position, among Saudi individuals. TDG rs4135050 (A/T) was investigated by genotyping 239, and 235 blood specimens were obtained from nonsmokers and smokers of cigarette respectively. T allele frequency was found which showed a significant protective effect on Saudi male smokers (OR = 0.64, p = 0.0187) compared to nonsmoking subjects, but not in female smokers. Furthermore, smokers aged less than 29 years, the AT and AT+TT genotypes decreased more than four times the risk of initiation of smoking related-diseases compare to the ancestral AA homozygous genotype. Paradoxically, the AT (OR = 3.88, p = 0.0169) and AT+TT (OR = 2.86, p = 0.0420) genotypes were present at a higher frequency in smoking patients aged more than 29 years as compared to nonsmokers at the same ages. Depending on the gender and age of patients, TDG rs4135050 may provide a novel biomarker for the early diagnosis and prevention of several diseases caused by cigarette smoking.

Sections du résumé

BACKGROUND
Thymine-DNA glycosylase (TDG) is an essential DNA-repair enzyme which works in both epigenetic regulation and genome maintenance. It is also responsible for efficient correction of multiple endogenous DNA lesions which occur commonly in mammalian genomes. Research of genetic variants such as SNPs, resulting in disease, is predicted to yield clinical advancements through the identification of sensitive genetic markers and the development of disease prevention and therapy. To that end, the main objective of the present study is to identify the possible interactions between cigarette smoking and the rs4135050 variant of the TDG gene, situated in the intron position, among Saudi individuals.
METHODS
TDG rs4135050 (A/T) was investigated by genotyping 239, and 235 blood specimens were obtained from nonsmokers and smokers of cigarette respectively.
RESULTS
T allele frequency was found which showed a significant protective effect on Saudi male smokers (OR = 0.64, p = 0.0187) compared to nonsmoking subjects, but not in female smokers. Furthermore, smokers aged less than 29 years, the AT and AT+TT genotypes decreased more than four times the risk of initiation of smoking related-diseases compare to the ancestral AA homozygous genotype. Paradoxically, the AT (OR = 3.88, p = 0.0169) and AT+TT (OR = 2.86, p = 0.0420) genotypes were present at a higher frequency in smoking patients aged more than 29 years as compared to nonsmokers at the same ages.
CONCLUSION
Depending on the gender and age of patients, TDG rs4135050 may provide a novel biomarker for the early diagnosis and prevention of several diseases caused by cigarette smoking.

Identifiants

pubmed: 30779328
doi: 10.1002/mgg3.590
pmc: PMC6465727
doi:

Substances chimiques

Thymine DNA Glycosylase EC 3.2.2.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e00590

Informations de copyright

© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

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Auteurs

Mikhlid Almutairi (M)

Zoology Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.

Abdullah Mohammad Alhadeq (A)

Zoology Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.

Rafa Almeer (R)

Zoology Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.

Mohammed Almutairi (M)

Zoology Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.

Mohammed Alzahrani (M)

Biology Department, College of Science, Al Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia.

Abdelhabib Semlali (A)

Groupe de Recherche en Écologie Buccale, Université Laval, Québec, Québec, Canada.
Department of Biochemistry, College of Science, King Saud University, Kingdom of Saudi Arabia, Riyadh.

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