TP53 codon 72 polymorphism as a risk factor for cardiovascular disease in a Brazilian population

Smith, Marília de Arruda Cardoso; Silva, M.D.A.; Cendoroglo, M. S.; Ramos, Luiz Roberto; Araújo, Lara Miguel Quirino; Lábio, Roger Willian de; Burbano, Rommel Rodrı́guez; Chen, E.S.; Payão, Spencer L.M.

doi:10.1590/s0100-879x2007001100007

Cited by 9 publications

(6 citation statements)

References 32 publications

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“…In the gender comparison, SNP rs1042522 was associated with a significant risk of obesity in males when compared to females. These results are inconsistence with a previous study conducted in the Brazilian population, in which they reported that women conferred significant risk to develop obesity with SNP rs1042522 (Smith et al, 2007).…”

Section: Discussioncontrasting

confidence: 99%

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The genetic association study of TP53 polymorphisms in Saudi obese patients

Sabir

Omri

Shaik

et al. 2019

Saudi Journal of Biological Sciences

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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.

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Section: Discussioncontrasting

confidence: 99%

“…In the present study, p53 Arg72 genotype samples showed lower HDL levels when compared with other genotypes; a similar pattern was also reported in the European population (Smith et al 2007). The exact mechanism between a low level of HDL and p53 is not known, but this may lead to other health complications such as cardiovascular problems.…”

Section: Discussionsupporting

confidence: 91%

The genetic association study of TP53 polymorphisms in Saudi obese patients

Sabir

Omri

Shaik

et al. 2019

Saudi Journal of Biological Sciences

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“…Our results corroborate a study conducted by Manfredi et al (2002) with 250 Italian individuals, which also did not find an association between the polymorphism of the p53 gene and AD. Smith et al (2007) analyzed 383 elderly patients with variants of AD and could not establish any association between this polymorphism and cardiovascular diseases. Alkhalaf et al (2007) found no association between codon 72 polymorphism of the p53 gene and CAD or diabetes in Kuwait individuals.…”

Section: Discussionmentioning

confidence: 99%

“…Regarding the association of dyslipidemia with p53 gene polymorphism and AD, Smith et al (2007) analyzed São Paulo (Brazil) population and found an association between the arginine allele and low levels of HDL cholesterol, which is considered a protective effect in the development of plaques of atherosclerosis. In the present study, this analysis was also performed, but we found no association.…”

Section: Discussionmentioning

confidence: 99%

Research Article Analysis of p53 gene polymorphism (codon 72) in symptomatic patients with atherosclerosis.

Lagares¹,

Silva²,

Barbosa³

et al. 2017

Genet. Mol. Res.

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ABSTRACT. Atherosclerosis is a multifactorial pathological disease that alters the morphology and function of arterial walls. The atheroma growth leads to vessel hardening and lumen narrowing, limiting the blood flow. The atheroma plaque can eventually break, expose highly thrombogenic material and lead to platelet activation and subsequent formation of a thrombus that may block blood flow in loco, or even leading to obstruction of other vessels with a smaller diameter. This process is one of the main determinants of the clinical manifestations of atherosclerosis, such as coronary artery disease, ischemic stroke, and peripheral arterial disease. Although the inflammatory theory about atherosclerosis is the most renowned one, observations point to common biological characteristics between cancer and atherosclerosis suggesting a possible association between p53 and atherosclerotic diseases. We collected peripheral blood samples from 200 individuals with clinical manifestations of atherosclerotic disease and 100 individuals without manisfestation of the disease to form the control group. DNA was subjected to molecular analysis (PCR) to identify the polymorphism of the p53 gene. We have not found any relationship between the polymorphism of the p53 gene and atherosclerosis in the population studied (P = 0.36). There was no relationship between atherosclerosis, polymorphism of p53 and the variables accounted: smoking habit (P = 0.72, 0.51 and 0.62 for smokers, non-smokers and former smokers respectively), alcohol consumption (P = 0.17 for individuals with drinking habits and 0.38 for those who do not consume alcohol beverage), systemic arterial hypertension (P = 0.60), diabetes mellitus (P = 0.34), and dyslipidemia (P = 0.89). Our population has a high rate of miscegenation and heterozygotes, and according to studies the arginine variant is more related to plaque formation because it induces apoptosis more frequently when compared to the proline variant. According to our results, there is no association between the polymorphism of the p53 gene, atherosclerosis and its risk factors in the population studied.

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“…Furthermore, studying the effect of Tp53 polymorphisms and their haplotypes on biochemical parameters revealed that codon 72 polymorphism in exon 4 significantly affect TG values. Compelling evidence suggests the fundamental role of p53 in adipose tissue metabolism and homeostasis, insulin resistance and development of metabolic diseases such as type 2 diabetes [ 40 ], cardiovascular diseases [ 41 ] and obesity [ 42 ]. A study on Brazilian population reported that Arg allele carriers showed lower HDL levels and a higher frequency of cardiovascular disease than Pro allele subjects [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Importance of TP53 codon 72 and intron 3 duplication 16 bp polymorphisms and their haplotypes in susceptibility to sarcopenia in Iranian older adults

et al. 2022

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Background Sarcopenia is described as age-related progressive skeletal muscle failure that results in marked reduction in the patient’s independence and life quality. In this study, we explored the association of TP53 exon 4 Arg72pro (rs1042522) and Intron 3 16-bp Del/Ins (rs17878362) polymorphisms and their haplotypes with sarcopenia, anthropometric, body composition and biochemical parameters. Methods A total of 254 older individuals (65 sarcopenic and 189 healthy) were recruited in this research and genotyped by PCR–RFLP. Linear regression was applied to find the correlation between TP53 polymorphism, and biochemical and anthropometric parameters. The correlation between TP53 polymorphism and haplotypes and the risk of sarcopenia was investigated by logistic regression. Results Arg/Pro genotype carriers was at a lower (ORadj = 0.175, 95% CI = 0.068 – 0.447; P < 0.001) risk of sarcopenia compared to the Arg/Arg group. In haplotypes analysis, Arg-Ins (ORadj: 0.484, 95% CI = 0.231 – 1.011, P = 0.043) and Pro-Ins (ORadj: 0.473, 95% CI = 0.210 – 1.068, P = 0.022) haplotypes showed decreased risk of developing sarcopenia. Moreover, in the case of codon 72 polymorphism, skeletal muscle mass, appendicular lean mass (ALM), skeletal muscle mass index (SMI), hand grip strength and Triglycerides, for Intron 3 16-bp Del/Ins polymorphism, albumin, calcium, cholesterol, and LDL were different, and for the haplotypes, skeletal muscle mass, SMI, ALM, HDL and triglycerides were significantly different between groups. Conclusions We suggested that the Arg/Pro genotype of the codon 72 polymorphism in exon 4 of TP53, and Arginine-Insertion and Proline-Insertion haplotypes might decrease the risk of sarcopenia in Iranian older adults.

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TP53 codon 72 polymorphism as a risk factor for cardiovascular disease in a Brazilian population

Cited by 9 publications

References 32 publications

The genetic association study of TP53 polymorphisms in Saudi obese patients

The genetic association study of TP53 polymorphisms in Saudi obese patients

Research Article Analysis of p53 gene polymorphism (codon 72) in symptomatic patients with atherosclerosis.

Importance of TP53 codon 72 and intron 3 duplication 16 bp polymorphisms and their haplotypes in susceptibility to sarcopenia in Iranian older adults

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