Almutairi Mikhlid, Mohammad Alhadeq Abdullah, Almeer Rafa, Almutairi Mohammed, Alzahrani Mohammed, Semlali Abdelhabib
Zoology Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Biology Department, College of Science, Al Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia.
Mol Genet Genomic Med. 2019 Apr;7(4):e00590. doi: 10.1002/mgg3.590. Epub 2019 Feb 18.
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.
胸腺嘧啶-DNA糖基化酶（TDG）是一种重要的DNA修复酶，在表观遗传调控和基因组维持中均发挥作用。它还负责有效修复哺乳动物基因组中常见的多种内源性DNA损伤。对诸如单核苷酸多态性（SNP）等导致疾病的基因变异进行研究，预计可通过识别敏感的遗传标记以及开发疾病预防和治疗方法来推动临床进展。为此，本研究的主要目的是确定沙特人群中吸烟与位于内含子位置的TDG基因rs4135050变异之间可能存在的相互作用。
对239例样本进行基因分型，研究TDG rs4135050（A/T），分别从非吸烟者和吸烟者中获取235份血液样本。
发现T等位基因频率对沙特男性吸烟者显示出显著的保护作用（与非吸烟受试者相比，比值比[OR]=0.64，p=0.0187），但对女性吸烟者无此作用。此外，年龄小于29岁的吸烟者中，与祖先AA纯合基因型相比，AT和AT+TT基因型使吸烟相关疾病发病风险降低四倍以上。矛盾的是，与同年龄的非吸烟者相比，年龄大于29岁的吸烟患者中，AT（OR=3.88，p=0.0169）和AT+TT（OR=2.86，p=0.0420）基因型的出现频率更高。
根据患者的性别和年龄，TDG rs4135050可能为早期诊断和预防几种由吸烟引起的疾病提供一种新的生物标志物。
