Laboratory of Human Molecular Genetics, Faculty of Medicine, University of Sfax, Av. Magida Boulila, 3029 Sfax, Tunisia.
Mol Biol Rep. 2012 Oct;39(10):9639-47. doi: 10.1007/s11033-012-1829-z. Epub 2012 Jun 28.
Genetic polymorphisms in DNA repair genes might influence the repair activities of the enzymes predisposing individuals to cancer risk. Owing to the presence of these genetic variants, interethnic differences in DNA repair capacity have been observed in various populations. The present study was undertaken to determine the allele and genotype frequencies of two common non-synonymous SNPs, XRCC3 p.Thr241>Met (C > T, rs861539) and XPD p.Lys751>Gln (T > G, rs13181) in a healthy Tunisian population and to compare them with HapMap ( http://www.hapmap.org/ ) populations. Also, we predicted their eventual functional effect based on bioinformatics tools. The genotypes of 154 healthy and unrelated individuals were determined by PCR-RFLP procedure. Our findings showed a close relatedness with Caucasians from European ancestry which might be explained by the strategic geographic location of Tunisia in the Mediterranean, thus allowing exchanges with Europeans countries. The in silico predictions showed that p.Thr241>Met substitution in XRCC3 protein was predicted as possibly damaging, indicating that it is likely to have functional consequences as well. To the best of our knowledge, this is the first study in this regard in Tunisia. So, these data could provide baseline database and help us to explore the relationship of XRCC3 and XPD polymorphisms with both cancer risk and DNA repair variability in our population.
DNA 修复基因中的遗传多态性可能会影响酶的修复活性,从而使个体易患癌症风险。由于存在这些遗传变异,不同种族之间的 DNA 修复能力存在差异,这在各种人群中都有观察到。本研究旨在确定两个常见的非同义 SNP(XRCC3 p.Thr241>Met(C > T,rs861539)和 XPD p.Lys751>Gln(T > G,rs13181)在一个健康的突尼斯人群中的等位基因和基因型频率,并将其与 HapMap(http://www.hapmap.org/)人群进行比较。此外,我们还根据生物信息学工具预测了它们可能的功能影响。通过 PCR-RFLP 程序确定了 154 名健康且无关个体的基因型。我们的研究结果显示与欧洲裔白种人密切相关,这可能是由于突尼斯在地中海的战略地理位置,从而允许与欧洲国家进行交流所导致的。计算机预测表明,XRCC3 蛋白中的 p.Thr241>Met 取代被预测为可能具有破坏性,这表明它很可能具有功能后果。据我们所知,这是突尼斯在这方面的首次研究。因此,这些数据可以提供基线数据库,并帮助我们在我们的人群中探索 XRCC3 和 XPD 多态性与癌症风险和 DNA 修复变异性的关系。