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沙特阿拉伯人群中肿瘤抑制基因 P53 错义突变与烟草物质使用之间的关联。

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

机构信息

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

Master's Student, Zoology Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.

出版信息

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

DOI:10.1371/journal.pone.0245133
PMID:33481818
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7822264/
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.

摘要

抑癌基因 TP53 及其下游基因 P21 和 MDM2 在 G1/S 细胞周期检验点对抗 DNA 损伤中发挥着关键作用。这些基因的多态性可能导致各种疾病的发生。本研究旨在通过比较沙特阿拉伯的吸烟者和非吸烟者人群,研究 P53、P21 和 MDM2 基因外显子区域的烟草物质使用(TSU)和单核苷酸多态性(SNP)之间的潜在关联。通过对 568 份血液样本进行基因分型,研究了 P53 rs1042522(C/G)、P21 rs1801270(A/C)和 MDM2 rs769412(A/G):283 份来自男性/女性吸烟者,285 份来自男性/女性非吸烟者。根据年龄、性别、吸烟时间和 TSU 类型,比较了吸烟者及其对照非吸烟者的结果。与非吸烟者相比,沙特吸烟者中杂合子 CG、纯合子 GG 和 CG+GG 基因型以及 rs1042522 的 G 等位基因与 TSU 显著相关。与非吸烟者相比,rs1801270 的 C 等位基因频率也与吸烟者的 TSU 相关(OR=1.33,p=0.049),与相同年龄的非吸烟者相比,与年龄≤29 岁的非吸烟者相比(OR=1.556,p=0.03280),与吸烟 7 年或更短时间的吸烟者相比(OR=1.596,p=0.00882),与吸食水烟的吸烟者相比(OR=1.608,p=0.04104)。然而,rs769412 的基因型和等位基因频率与 TSU 无显著关联。选择的 P53 SNP 与 TSU 密切相关,可能与沙特阿拉伯人群中 TSU 诱导的疾病有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a380/7822264/78052eaa24fd/pone.0245133.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a380/7822264/5e3697ecfa6a/pone.0245133.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a380/7822264/8e440e7eaecf/pone.0245133.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a380/7822264/78052eaa24fd/pone.0245133.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a380/7822264/5e3697ecfa6a/pone.0245133.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a380/7822264/8e440e7eaecf/pone.0245133.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a380/7822264/78052eaa24fd/pone.0245133.g003.jpg

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