OncoTargets and Therapy (Nov 2016)

Effect of smoking on the genetic makeup of toll-like receptors 2 and 6

  • Kohailan M,
  • Alanazi M,
  • Rouabhia M,
  • Alamri A,
  • Parine NR,
  • Alhadheq A,
  • Basavarajappa S,
  • Abdullah Al-Kheraif AA,
  • Semlali A

Journal volume & issue
Vol. Volume 9
pp. 7187 – 7198

Abstract

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Muhammad Kohailan,1 Mohammad Alanazi,1 Mahmoud Rouabhia,2 Abdullah Alamri,1 Narasimha Reddy Parine,1 Abdullah Alhadheq,1 Santhosh Basavarajappa,3 Abdul Aziz Abdullah Al-Kheraif,3 Abdelhabib Semlali1 1Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia; 2Département de Stomatologie, Faculté de Médecine Dentaire, Groupe de Recherche en Écologie Buccale, Université Laval, Québec City, QC, Canada; 3Dental Biomaterial Research Chair, Department of Dental Health, College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia Background: Cigarette smoking is a major risk factor for lung cancer, asthma, and oral cancer, and is central to the altered innate immune responsiveness to infection. Many hypotheses have provided evidence that cigarette smoking induces more genetic changes in genes involved in the development of many cigarette-related diseases. This alteration may be from single-nucleotide polymorphisms (SNPs) in innate immunity genes, especially the toll-like receptors (TLRs).Objective: In this study, the genotype frequencies of TLR2 and TLR6 in smoking and nonsmoking population were examined.Methods: Saliva samples were collected from 177 smokers and 126 nonsmokers. The SNPs used were rs3804100 (1350 T/C, Ser450Ser) and rs3804099 (597 T/C, Asn199Asn) for TLR2 and rs3796508 (979 G/A, Val327Met) and rs5743810 (745 T/C, Ser249Pro) for TLR6.Results: Results showed that TLR2 rs3804100 has a significant effect in short-term smokers (OR =2.63; P=0.04), and this effect is not observed in long-term smokers (>5 years of smoking). Therefore, this early mutation may be repaired by the DNA repair system. For TLR2 rs3804099, the variation in genotype frequencies between the smokers and control patients was due to a late mutation, and its protective role appears only in long-term smokers (OR =0.40, P=0.018). In TLR6 rs5743810, the TT genotype is significantly higher in smokers than in nonsmokers (OR =6.90). The effect of this SNP is observed in long-term smokers, regardless of the smoking regime per day.Conclusion: TLR2 (rs3804100 and rs3804099) and TLR6 (rs5743810) can be used as a potential index in the diagnosis and prevention of more diseases caused by smoking. Keywords: polymorphism, toll-like receptor, genotyping, smoking, TLR2, TLR6

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