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No association of the p53 codon 72 polymorphism with malaria in Ghanaian primiparae and Rwandan children.

ABSTRACT: The p53 protein is a key cell-signaling mediator integrating host responses to various types of stress. A common polymorphism of the encoding TP53 gene (codon 72, Pro > Arg, rs1042522) is associated with susceptibility to virus-related and other cancers. The p53 has also been shown to be central for successful Plasmodium liver stage infection. We examined whether the polymorphism is associated with P. falciparum infection in Ghanaian primiparae and Rwandan children. The allele frequency of TP53 codon 72 Arg was 0.30 among 314 Ghanaian primiparae and 0.31 among 545 Rwandan children, respectively, and it was not associated with infection prevalence or parasite density. This does not exclude p53 to be of pathophysiological relevance in malaria but argues against a major respective role of the TP53 codon 72 polymorphism.

SUBMITTER: Gai PP

PROVIDER: S-EPMC4047741 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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No association of the p53 codon 72 polymorphism with malaria in Ghanaian primiparae and Rwandan children.

Gai Prabhanjan P PP Meese Stefanie S Bedu-Addo George G Gahutu Jean Bosco JB Mockenhaupt Frank P FP

The American journal of tropical medicine and hygiene 20140407 6

The p53 protein is a key cell-signaling mediator integrating host responses to various types of stress. A common polymorphism of the encoding TP53 gene (codon 72, Pro > Arg, rs1042522) is associated with susceptibility to virus-related and other cancers. The p53 has also been shown to be central for successful Plasmodium liver stage infection. We examined whether the polymorphism is associated with P. falciparum infection in Ghanaian primiparae and Rwandan children. The allele frequency of TP53 ...[more]

PMID: 24710610

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p53 codon 72 polymorphism and breast cancer risk: A meta-analysis.

Project description:p53 is a tumor suppressor gene and plays important roles in the etiology of breast cancer. Studies have produced conflicting results concerning the role of p53 codon 72 polymorphism (G>C) on the risk of breast cancer; therefore, a meta-analysis was performed to estimate the association between the p53 codon 72 polymorphism and breast cancer. Screening of the PubMed database was conducted to identify relevant studies. Studies containing available genotype frequencies of the p53 codon 72 polymorphism were selected and a pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the association. Sixty-one published studies, including 28,539 breast cancer patients and 32,788 controls were identified. The results suggest that variant genotypes are not associated with breast cancer risk (Pro/Pro + Arg/Pro vs. Arg/Arg: OR=1.016, 95% CI=0.931-1.11, P=0.722). The symmetric funnel plot, Egger's test (P=0.506) and Begg's test (P=0.921) were all suggestive of the lack of publication bias. This meta-analysis suggests that the p53 codon 72 Pro/Pro + Arg/Pro genotypes are not associated with an increased risk of breast cancer. To validate the association between the p53 codon 72 polymorphism and breast cancer, further studies with larger numbers of participants worldwide are required.

| S-EPMC3671901 | biostudies-literature

p53 codon 72 polymorphism and recurrent pregnancy loss: a meta-analysis.

Project description:BackgroundArg72Pro polymorphism of the p53 tumour suppressor gene have been associated with recurrent pregnancy loss. However, results were inconsistent. We performed this metaanalysis to drive amore precise estimation of association between p53 codon 72 polymorphism and recurrent pregnancy loss.MethodsElectronic searche of PubMed was conducted to select studies. Case-control studies containing available genotype frequencies of Arg72Pro were chose, and Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association.Results4 case-control studies including 523 cases and 378controls were identified. This meta-analysis showed that individuals with the homozygous Pro/Pro genotype had increased risk of recurrent pregnancy loss (OR = 1.85, 95% CI: 1.078 ~ 3.173, p = 0.025) in the pooled analyses. An symmetric funnel plot, the Egger's test (P = 0.497), and the Begg- test (P = 0.85) were all suggestive of the lack of publication bias.ConclusionThis meta-analysis supports the idea that p53 condon72 Pro/Pro genotype is associated with increased risk of recurrent pregnancy loss. To draw comprehensive and true conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine associations between p53 codon 72 polymorphism and recurrent pregnancy loss.

| S-EPMC3220438 | biostudies-literature

p53 codon 72 polymorphism and hematological cancer risk: an update meta-analysis.

Project description:BackgroundPrevious studies on the association of p53 codon 72 (Arg72Pro) polymorphism with hematological malignancies risk have produced conflicting results. The purpose of this meta-analysis is to define the effect of p53 Arg72Pro polymorphism on hematological malignancies risk.Methodology/principal findingsThrough searching PubMed databases (or hand searching) up to April 2012 using the following MeSH terms and keywords: "p53", "codon 72" "polymorphism" and "leukemia", or "lymphoma", or "myeloma", thirteen were identified as eligible articles in this meta-analysis for p53 Arg72Pro polymorphism (2,731 cases and 7, 356 controls), including nine studies on leukemia (1,266 cases and 4, 474 controls), three studies on lymphoma (1,359 cases and 2,652 controls), and one study on myeloma. The overall results suggested that p53 Arg72Pro polymorphism was not associated with hematological malignancies risk. In stratified analyses, significantly increased non-Hodgkin lymphomas risk was found in p53 Arg72Pro polymorphism heterozygote model (Arg/Pro vs. Arg/Arg: OR = 1.18, 95%CI: 1.02-1.35) and dominant model (Arg/Pro+Pro/Pro vs. Arg/Arg: OR = 1.18, 95%CI: 1.03-1.34), but no significant association was found between leukemia risk and p53 Arg72Pro polymorphism. Further studies showed no association between leukemia risk and p53 Arg72Pro polymorphism when stratified in subtypes of leukemias, ethnicities and sources of controls.Conclusions/significanceThis meta-analysis indicates that the p53 Arg72Pro polymorphism may contribute to susceptibility to non-Hodgkin lymphomas.

| S-EPMC3454327 | biostudies-literature

Cancer susceptibility polymorphism of p53 at codon 72 affects phosphorylation and degradation of p53 protein.

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| S-EPMC3093897 | biostudies-literature

Evaluating the association between p53 codon 72 Arg>pro polymorphism and risk of ovary cancer: a meta-analysis.

Project description:AimAllelic polymorphism in codon 72 of the p53 tumor suppressor gene causes imbalance of p53 protein expression. Earlier studies have shown association between allelic polymorphism in codon 72 of the p53 gene with risk of ovary cancer (OC); however the results are inconclusive and conflicting. Therefore, we performed this meta-analysis to investigate the relation between p53 codon 72 Arg>Pro polymorphism and overall OC susceptibility.MethodsWe searched all eligible published studies based on the association between codon 72 of the p53 Arg>Pro polymorphism and risk of OC. Data were pooled together from individual studies and meta-analysis was performed. Pooled odds ratios (ORs) and 95% CI were calculated for allele contrast, homozygous, heterozygous, dominant and recessive genetic models.ResultsA total of twelve studies comprising of 993 OC cases and 1264 healthy controls were included in this meta-analysis. Overall, no significant association was detected for Pro allele carrier (Pro vs. Arg: p = 0.916; OR = 0.980, 95% CI = 0.677 to 1.419), homozygous (Pro/Pro vs. Arg/Arg: p = 0.419; OR = 0.731, 95% CI = 0.341 to 1.564), heterozygous (Arg/Pro vs. Arg/Arg: p = 0.248; OR = 1.237, 95% CI = 0.862 to 1.773), dominant (Pro/Pro+Arg/Pro vsArg/Arg: p = 0.699; OR = 1.089, 95% CI = 0.706 to 1.681), and recessive (Pro/Pro vs Arg/Arg+Arg/Pro: p = 0.329; OR = 0.754, 95% CI = 0.428 to 1.329) genetic models, respectively. Also, in the stratified analysis by ethnicity, no significant association of this polymorphism with risk of OC was found in the Caucasian population.ConclusionsThis meta-analysis suggested that codon 72 of the p53 Arg>Pro polymorphism may not significantly contribute in ovary cancer susceptibility. However, future large studies with gene-gene and gene-environment interactions are needed to validate these findings.

| S-EPMC3991634 | biostudies-literature

Association of p53 codon 72 polymorphism with susceptibility to hepatocellular carcinoma in a Chinese population from northeast Sichuan.

Project description:The p53 tumor suppressor gene is key in tumor development and progression, and the single nucleotide polymorphism (SNP) of the p53 gene codon 72 (p53Arg/Pro) changes the structure of the protein. In addition, it affects its activity, which may affect cancer risk. The aim of the present study was to investigate the association between p53 codon 72 polymorphism and susceptibility to hepatocellular carcinoma (HCC) in a Chinese population from northeast Sichuan. A total of 342 HCC patients and 347 non-cancer control subjects were recruited, and the polymorphism of p53 codon 72 was measured by TaqMan® minor groove binder fluorescent quantitative polymerase chain reaction assay. The distribution frequency of p53 sites of arginine (Arg)/Arg, Arg/proline (Pro), Pro/Pro were 18.4, 48.8 and 32.8% in the control group, as compared with 18.7, 49.9 and 31.4% in the case group, which indicated that there was no difference between two groups (χ2=0.14; P=0.93). Upon further stratification with smoking, alcohol consumption, gender and hepatitis B virus (HBV) infection, no risk increasing genotype was identified. However, interactions between p53 codon 72 SNP and smoking, alcohol consumption and HBV infection may increase the risk of HCC [smoking odds ratio (OR), 2.00; 95% confidence interval (CI), 1.21-3.29; alcohol consumption OR, 1.87; 95% CI, 1.08-3.26; HBV infection OR, 1.84; 95% CI, 1.10-3.08]. No significant association was identified between p53 codon 72 polymorphism and HCC, and it may not have an independent effect on the susceptibility to HCC in a Chinese population from northeast Sichuan. However, interaction between genetic factors and environment exposure significantly increased the risk of HCC.

| S-EPMC5351203 | biostudies-literature

The codon 72 polymorphism of p53 influences cell fate following nutrient deprivation.

Project description:The TP53 gene is distinguished as the most frequently mutated gene in cancer. Unlike most cancer-relevant genes, the TP53 gene is also distinguished by the existence of coding region polymorphisms that alter p53 sequence, and in some cases, also alter p53 function. A common coding region variant at amino acid 72 of p53 encodes either proline (P72) or arginine (R72). P72 is the ancestral variant and is most common in populations near the equator. The frequency of the R72 variant increases in a linear manner with latitude. To date, why the R72 variant arose in humans and was possibly selected for has remained unclear. Here-in we show that this single nucleotide polymorphism (SNP) influences the phosphorylation of p53 and the transactivation of the key p53 target CDKN1A (p21) specifically in response to nutrient deprivation, but not in response to conventional cytotoxic agents. Following activation of the kinase AMPK, R72 cells show increased phosphorylation on serine-15 and increased transactivation of the cyclin-dependent kinase inhibitor CDKN1A (p21) and the metabolic response genes PPARGC1B (PGC-1?) and PRKAB2 (AMPK-?2). This is accompanied by increased growth arrest and decreased apoptosis in R72 cells compared with P72 cells. The combined data fit best with the hypothesis that the R72 polymorphism confers increased cell survival in response to nutrient deprivation. This differential response to nutrient deprivation may explain part of selection for this SNP at northern latitudes, where nutrient deprivation might have been more frequent.

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ТР53 Codon 72 Polymorphism and Human Papilloma

Project description:Background: The aim of this study was to ascertain the magnitude of association of gene ТР53 Arg72Pro polymorphic

| S-EPMC6948899 | biostudies-literature

Association between the p53 codon 72 polymorphism and primary open-angle glaucoma risk: Meta-analysis based on 11 case-control studies.

Project description:The TP53 is important in functions of cell cycle control, apoptosis, and maintenance of DNA integrity. Studies on the association between p53 codon 72 polymorphism and primary open-angle glaucoma (POAG) risk have yielded conflicting results. Published literature from PubMed and Web of Science databases was retrieved. All studies evaluating the association between p53 codon 72 polymorphisms and POAG were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated. Eleven separate studies including 2541 cases and 1844 controls were pooled in the meta-analysis. We did not detect a significant association between POAG risk and p53 codon 72 polymorphism overall population except allele genetic model (C vs. G: OR = 0.961, 95% CI = 0.961-0.820, P = 0.622). In the stratified analysis for Asians and Caucasians, there was an association between p53 codon 72 polymorphism and POAG. In the dominant model in the overall population and by ethnicity subgroups, the highest elevated POAG risk was presented. In summary, these results indicate that p53 codon 72 polymorphism is likely an important genetic factor contributing to susceptibility of POAG. However, more case-controls studies based on larger sample size and stratified by ethnicity are suggested to further clarify the relationship between p53 codon 72 polymorphism and POAG.

| S-EPMC5168918 | biostudies-literature

Primary open angle glaucoma in a Caucasian population is associated with the p53 codon 72 polymorphism.

Project description:Apoptosis has been implicated as the mechanism for retinal ganglion cell death in primary open-angle glaucoma (POAG), a complex neurodegenerative disease. There have been inconsistent reports regarding increased risk of POAG and a polymorphism (Arg72Pro) within the tumor suppressor gene, p53. The goal of this study was to examine the role of this polymorphism in susceptibility to POAG in a Caucasian population from the United States.We generated genotypes in 191 unrelated Caucasian POAG patients and 167 unrelated Caucasian controls for the following polymorphisms within p53: rs1042522 (Arg72Pro), rs17878362 (16 bp Ins/Del), and rs1800371 (Pro47Ser) by PCR amplification followed by restriction digestion and sequence analysis.There was a significant difference in genotypic frequencies for rs1042522 (Arg72Pro) between POAG patients and controls (chi(2)= 9.56, p=0.008). Individuals who were homozygous for the arginine allele have a 1.9 fold significantly increased risk of developing glaucoma (95%CI: 1.16-2.82, p=0.01). Interestingly, we found that the frequency of the arginine allele was even higher in the normal-tension glaucoma (NTG) subtype compared to high-tension POAG (0.81 versus 0.76).Our preliminary results indicate that the arginine variant of rs1042522 within p53 is associated with increased risk of POAG. This variant has increased apoptotic potential, thus the retinal ganglion cells in carriers of the arginine allele may have greater susceptibility to apoptosis.

| S-EPMC2751801 | biostudies-literature

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