The genetic association study of TP53 polymorphisms in Saudi obese patients

Abstract

Obesity is a multifactorial metabolic disorder characterized by low grade chronic inflammation. Rare and novel mutations in genes which are vital in several key pathways have been reported to alter the energy expenditure which regulates body weight. The TP53 or p53 gene plays a prominent role in regulating various metabolic activities such as glycolysis, lipolysis, and glycogen synthesis. Recent genome-wide association studies reported that tumor suppressor gene p53 variants play a critical role in the predisposition of type 2 diabetes and obesity. Till date, no reports are available from the Arabian population; hence the present study was intended to assess the association between p53 variants with risk of obesity development in the Saudi population. We have selected three p53 polymorphisms, rs1642785 (C > G), and rs9894946 (A > G), and rs1042522 (Pro72Arg; C > G) and assessed their association with obesity risk in the Saudi population. Phenotypic and biochemical parameters were also evaluated to check their association with p53 genotypes and obesity. Genotyping was carried out on 136 obese and 122 normal samples. We observed that there is significantly increased prevalence p52 Pro72Arg (rs1042522) polymorphism in obese persons when compared to controls at GG genotype in overall comparison (OR: 2.169, 95% CI: 1.086-4.334, p = 0.02716). Male obese subjects showed three-fold higher risk at GG genotype (OR: 3.275, 95% CI: 1.230-8.716, p = 0.01560) and two-fold risk at G allele (OR: 1.827, 95% CI: 1.128-2.958, p = 0.01388) of p53 variant Pro72Arg respectively. This variant has also shown significant influence on cholesterol, LDL level, and random insulin levels in obese subjects (p ≤ 0.05). In conclusion, p53 Pro72Arg variant is highly prevalent among obese individuals and may act as a genetic modifier for obesity development among Saudis.

The association between TP53 rs1625895 polymorphism and the risk of sarcopenic obesity in Iranian older adults: a case-control study

“…Elevated expression and activity of p53 was proven to occurs in the adipose tissue of obese mice [ 34 ]. In 2019, Sabir et al observed that p53 rs1042522 mutant allele is more frequent among obese individuals in Saudi population and suggested that p53 may be considered as genetic modifier for obesity development [ 35 ]. The p53 rs1042522 polymorphism (Pro72Arg) impression on body metabolism was also inspected in humanized p53 mice [ 36 ].…”

The Association Between TP53 rs1625895 Polymorphism and the Risk of Sarcopenic Obesity in Iranian Older Adults: A Case-Control Study

“…Elevated expression and activity of p53 was proven to occurs in the adipose tissue of obese mice (42). In 2019, Sabir et al observed that p53 rs1042522 mutant allele is more frequent among obese individuals in Saudi population and suggested that p53 may be considered as genetic modi er for obesity development (43). The p53 rs1042522 polymorphism ( Pro72Arg) impression on body metabolism was also inspected in humanized p53 mice (44).…”

“…According to our best knowledge, there is no study on association betweenTP53 rs1625895 and lipid levels. Sabir et al 2019 reported that Arg72 variant of TP53 increased BMI, W/H ratio, cholesterol, LDL level, and insulin levels (43).…”

Molecular and <em>in silico</em> Study of TP53 Codon 72 Polymorphism (rs1042522) in a Population Exposed to High Background Radiation in Mamuju-West Sulawesi

“…The proline-to-arginine substitution can also lead to the loss of hydrophobic interactions with other amino acids. In addition, the charges possessed by mutant amino acids can cause repulsion with neighboring amino acids [21]. The electrostatic surface charge calculations also reveal that the interface of codon 72, which is equally positive and negative for proline, becomes mostly positive for arginine (Figs.…”

“…Other SNPs, particularly those located in the DBD region of TP53, would likely better reflect variations among individual sensitivities to radiation exposure. TP53 is a well-known polymorphic gene [7], with more than 200 polymorphic variants reported in the exon, promoter, and intron regions [21]. The hotspot mutations that affect TP53 are usually located in the DBD (exons 5-8), which plays key roles in the transcriptional activation of TP53 target genes [23].…”