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Clinical Trial
. 2021 Jan 22;16(1):e0245133.
doi: 10.1371/journal.pone.0245133. eCollection 2021.

Association between tobacco substance usage and a missense mutation in the tumor suppressor gene P53 in the Saudi Arabian population

Mikhlid H Almutairi  1 , Bader O Almutairi  1 , Turki M Alrubie  2 , Sultan N Alharbi  3 , Narasimha R Parine  4 , Abdulwahed F Alrefaei  1 , Ibrahim Aldeailej  5 , Abdullah Alamri  4 , Abdelhabib Semlali  6
Affiliations
Clinical Trial

Association between tobacco substance usage and a missense mutation in the tumor suppressor gene P53 in the Saudi Arabian population

Mikhlid H Almutairi et al. PLoS One. .

Abstract

The tumor suppressor gene TP53 and its downstream genes P21 and MDM2 play crucial roles in combating DNA damage at the G1/S cell cycle checkpoint. Polymorphisms in these genes can lead to the development of various diseases. This study was conducted to examine a potential association between tobacco substance usage (TSU) and single-nucleotide polymorphism (SNP) at the exon regions of the P53, P21, and MDM2 genes by comparing populations of smokers and non-smokers from Saudi Arabia. P53 rs1042522 (C/G), P21 rs1801270 (A/C), and MDM2 rs769412 (A/G) were investigated by genotyping 568 blood specimens: 283 from male/female smokers and 285 from male/female non-smokers. The results obtained from the smokers and their control non-smokers were compared according to age, sex, duration of smoking, and type of TSU. Heterozygous CG, homozygous GG, and CG+GG genotypes, as well as the G allele of rs1042522 were significantly associated with TSU in Saudi smokers compared with non-smokers. The C allele frequency of rs1801270 was also associated with TSU in smokers (OR = 1.33, p = 0.049) in comparison with non-smokers, in younger smokers (≤29 years) (OR = 1.556, p = 0.03280) in comparison with non-smokers of the same age, in smokers who had smoked cigarettes for seven years or less (OR = 1.596, p = 0.00882), and in smokers who had consumed shisha (OR = 1.608, p = 0.04104) in comparison with the controls. However, the genotypic and allelic frequencies for rs769412 did not show significant associations with TSU in Saudis. The selected SNP of P53 was strongly associated with TSU and may be linked to TSU-induced diseases in the Saudi Arabian population.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. The 3D structures of normal and mutated P53 proteins.
Panel (A) shows the major domain structure of a P53 protein. Panel (B) shows the 3D structure of the wild-type P53 protein (P72). Panel (C) shows the 3D structure of a P53 protein with an SNP (P72R).
Fig 2
Fig 2. The 3D structures of normal and mutated P21 proteins.
Panel (A) shows the major domain structure of a P21 protein. Panel (B) shows the 3D structure of a normal P21 protein (R31). Panel (C) shows the 3D structure of a P21 protein with an SNP (R31S).
Fig 3
Fig 3. The 3D structures of normal and mutated MDM2 proteins.
See this image and copyright information in PMC

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