Pro Allele Research Articles

TP53 Arg72Pro polymorphism and its relationship with major depressive disorder

This study investigates the association between the TP53 Arg72Pro polymorphism and major depressive disorder (MDD) using a case-control approach. The study sample comprised 97 individuals: 16 in the case group diagnosed with MDD and 81 in the control group. Genotyping was conducted using the PCR-RFLP technique, with the genotypic frequencies calculated by direct counting and statistical significance at 5% (P<0.05). Results indicated that the TP53 Arg72Pro polymorphism's Pro allele was significantly more frequent in the MDD case group. These findings suggest that the Pro allele is associated with an increased risk of developing major depressive disorder.

Abstract 7326: TP53 p.Pro47Ser polymorphism in breast cancer susceptibility in Mali

Abstract Background: The aim of this study was to assess the potential association of p.Pro47Ser polymorphisms of TP53 with the risk of developing breast cancer in the Malian population. Methods: We analyzed DNA samples from 72 breast cancer patients and 121 unrelated healthy, age-matched individuals to examine the presence of the polymorphisms. The genotyping of TP53 polymorphism was performed using PCR-RFLP and HRM (high-resolution melting) methods. Results: The genotypic frequencies of PP, PS, and SS were found to be 63.9% PP, 30.6% PS, and 5.6% SS in breast cancer patients, compared to 70.2% PP, 22.3% PS, and 7.4% SS in the control group. The frequencies of P and S alleles of TP53 p.P47S polymorphism were 79.2% vs 81.4%, 20.8% vs 18.6%, and 5% vs 4.5% in patients and controls, respectively. In this study, no significant correlation was observed between TP53 p.Pro47Ser polymorphism and breast cancer in the Malian population (Pro/Ser vs Pro/Pro: OR = 1.55, 95% CI = 0.80-3.05, P = 0.19; Ser/Ser vs Pro/Pro: OR = 1.27, 95% CI = 0.34-4.74, P = 0.71; and Ser vs Pro allele: OR = 1.39, 95% CI = 0.80-2.32, P = 0.24). Conclusion: Despite the absence of a genetic association between TP53 p.Pro47Ser and the risk of breast cancer in Malian patients, our findings suggest that individuals carrying at least one minor Ser allele are not protected against the disease. Citation Format: Brehima Diakite, Yaya Kassogue, Mamoudou Maiga, Oumar Kassogue, Kadidiatou Cisse, Fousseyni Diarra, Cheick Traore B. Traore, Bakarou Kamate, Jane L. Holl, Lifang Hou. TP53 p.Pro47Ser polymorphism in breast cancer susceptibility in Mali [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7326.

TP53 Arg72Pro Genetic Polymorphism and Young Women with Breast Cancer: Case-Control Study in Brazil

Introduction: Breast cancer is the most common cancer in women and incidence and mortality rates are increasing among young women worldwide, including Brazil. TP53 Arg72Pro polymorphism (rs1042522) has been associated with breast cancer, due to its important role in cell cycle that impacts the development of cancer. Objective: To determine the magnitude of the association between TP53 Arg72Pro polymorphism and breast cancer development in young Brazilian women. Method: Hospital-based case-control study conducted in Rio de Janeiro with 268 confirmed breast cancer cases and 277 controls with women enrolled among hospitalized patients without neoplastic diseases or their companions at three public hospitals. Results: The genotype frequency was 46.57% for Arg/Pro, 35.74% for Arg/Arg, and 17.69% for Pro/Pro among healthy controls and 41.04% for Arg/Pro, 46.64% for Arg/Arg, and 12.31% for Pro/Pro among breast cancer cases. The genotypes Pro/Pro (OR=0.46; 95% CI=0.27-0.80, in comparison with Arg/Arg genotype) and Pro allele in dominant model (OR=0.65; 95% CI=0.45-0.92, in comparison with Arg/Arg genotype) were statistically associated with a protective effect for breast cancer among young Brazilian women. Also, family history of breast or ovary cancer (OR=2.18; 95% CI=1.37-3.46) and tobacco use (OR=1.74; 95% CI=1.14-2.68) were statistically associated with breast cancer. Conclusion: Further studies are necessary to confirm that Arg72Pro polymorphism can be a protective factor for breast cancer development among young women, since ethnicity can influence genotypes frequencies and the risk of developing breast cancer.

Impact of Arg72Pro polymorphism in P53 gene in cancer susceptibility in Algerian population

TP53 is a tumor suppressor gene involved in the development of several types of cancer. It has been reported that single nucleotide polymorphism in codon 72 of this gene, causing substitution of a Proline for an Arginine, may increase the risk of carcinogenesis. The objective of this study was to assess the frequency of the Arg72Pro polymorphism and to look for a possible association between this polymorphism and the occurrence of cancer. Our study concerned 82 DNA samples collected from the DNA bank of the Laboratory of Biology and Molecular Genetics of the Constantine University 3, and grouped 2 populations: 41 controls and 41 patients with one of three types of cancer: breast cancer, cervical cancer and lung cancer. This polymorphism was detected with PCR / RFLP. The results obtained in our study revealed a significant difference between the two patient and control groups for the heterozygous CG genotype (OR = 0.13, P = 0.001), which makes it possible to conclude that the CG genotype constitutes a risk factor in the occurrence cancer. However, the study showed that there is no difference between the Pro allele and the Arg allele in the patients compared to the controls (OR = 0.95, P = 0.87), which could rule out the possible association between the Arg72Pro polymorphism and the onset of cancer.

TP53 Codon 72 Polymorphism and the Risk of Colorectal Cancer in an Azerbaijani Population.

We aimed to evaluate the association between the TP53 Arg72Pro gene polymorphism and risk of colorectal cancer in an Azerbaijani population. A total of 141 patients with colorectal cancer and 150 gender- and age-matched controls were involved in the study. The genotypes of the TP53 gene Arg72Pro polymorphism were detected by polymerase chain reaction-based restriction fragment length polymorphism analysis. We found that the heterozygous genotypes Arg/Pro (odds ratio, 1.128; 95% CI, 0.657-1.937) and mutant Pro/Pro (odds ratio, 1.274; 95% CI, 0.648-2.504) were more frequent in colorectal cancer patients compared to healthy controls. The frequency of the mutant Pro allele (odds ratio, 1.122; 95% CI, 0.809-1.554) was revealed in 47.5% of colorectal cancer patients and in 44.7% of healthy controls. There was no association observed between TP53 Arg72Pro polymorphism and risk of colorectal cancer in an Azerbaijani population (P > .05). Our findings indicate a lack of relationship between TP53 Arg72Pro polymorphism and risk of colorectal cancer. Furthermore, we have found no statistical differences in the frequency of genotype and allele by sex, age, histological grade, tumor stage, smoking status, and alcohol consumption in this study.

Low-Cost Genetic and Clinical Predictors of Response and Toxicity of Platinum-Based Chemotherapy in Advanced Non-Small Cell Lung Cancer.

BackgroundThis study aimed to evaluate for the first time whether certain genetic and clinical factors could serve as minimally invasive predictors of survival and toxicity to platinum-based chemotherapy in advanced lung adenocarcinoma.MethodsThe study included 121 advanced lung adenocarcinoma patients treated with platinum-based dublets until progression or unacceptable toxicity. Response was evaluated using standard radiological methods and toxicity graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Genotyping was performed using PCR-RFLP. Statistical significance was set at P < .05.ResultsNo significant influence of the examined polymorphisms on the occurrence of high-grade toxicity was detected. However, TP53 72Pro allele carriers were more prone to nausea (P = .037) and thrombocytopenia (P = .051). Anemia and neuropathy occurred more frequently in XRCC1 399Arg allele carriers (Pearson χ2 test, P = .025 and P = .004 respectively). RAD51 135CC carriers were significantly more prone to neutropenia (P = .027).ConclusionsA set of easily determined genetic and clinical predictors of survival and specific toxicity profiles of platinum-based chemotherapy in advanced lung adenocarcinoma were determined in this study, which might be useful for the construction of population-specific, time- and cost-efficient prognostic and predictive algorithms.

Assessment of the role of the leu28pro polymorphic marker of the apoe gene in diabetic nephropathy

The aim of this study was to study 129 patients with type 2 diabetes and 110 healthy people to determine whether the Leu28Pro polymorphic markers of the APOE gene are associated with the development of diabetic nephropathy (DN). Patients in the main group: 65 patients with a disease duration of up to 10 years, without diabetic nephropathy (33 patients) and with diabetic nephropathy (32 patients), 64 patients with diabetes lasting more than 10–20 years, with no diabetic nephropathy (31 patients) and diabetic nephropathy (33 patients). Genotyping was carried out by polymerase chain reaction. The study showed that the association of the Pro allele and the Leu/Pro genotype of the ENOS3 gene play a role in the development of diabetic nephropathy in patients with type 2 diabetes mellitus in the studied Uzbek nation.

Polymorphism of TP53 gene and the risk of high human papillomavirus load in cervical epithelial cells

BackgroundCervical cancer is mostly caused by persistent human papillomavirus infection. Host genetic variables, such as polymorphisms, may play a role in the development of cervical cancer and may be a risk factor for HPV-induced carcinogenesis. AimsTo investigate the association between TP53 Pro72Arg polymorphism and the high HPV loads in cervical epithelial cells of women older than 30 years. Subjects and methods154 women infected with HPV and 156 healthy women were recruited into a case–control study. Total DNA was isolated from scrapings of epithelial cells from the cervical canal. Genotyping of the TP53 Pro72Arg polymorphism was carried out using allele-specific PCR. Quantitative analysis of human papillomavirus DNA was performed by the AmpliSens®HPV HCR screen- titre-FRT test system. ResultsNo statistically significant difference was detected between allele and genotype frequencies (p = 0.54 and p = 0.67 respectively) in either women with a medium viral load (3–4 log HPV genomes per 100 thousand human cells) or the control group. The frequencies of the ТР53 Arg72 allele and ТР53 72Arg/Arg genotype were significantly higher in women with a high viral load (above 4 log HPV genomes per 100 thousand human cells) than in the control group (OR = 2.36, p = 0.001 and OR = 2.63, p = 0.002 respectively). The ТР53 Pro72 allele and ТР53 72Pro/Pro genotype are associated with a decreased risk of high HPV load group (OR = 0.42, p = 0.001 and OR = 0.14, p = 0.002 respectively). ConclusionThe risk of developing a high viral load in cervical epithelial cells is associated with the TP53 72Arg allele and the TP53 72Arg/Arg genotype in HPV-positive women.

Features of the distribution of polymorphic variants of candidate genes and clinical presentation of long-term period in patients with myocardial infarction and diabetic nephropathy

Abstract Objective To evaluate rate of distribution of the NOS3, APOE, SLCO1B1 and CYP2C19 genes and features of clinical presentation of the long-term period (12 months) in patients with myocardial infarction (MI) and diabetic nephropathy (DN). Materials and methods Examined 160 patients treated for MI (Males – 58,2%; 41,8% – females, average age 67,1±4,2 years). Patients were divided into 2 groups: the first (I) – 84 patients with MI and DN, the second (II) – 76 persons with MI without DN. The samples were comparable by sex and age. Determination of genotypic accessories genes NOS3 (rs2070744), APOE (rs769452), CYP2C19 (rs4986893 and rs4244285) and SLCO1B1 (rs4149056) were based on the analysis of genomic human DNA by polymerase chain reaction. The long-term follow-up period was 1 year. Results Analysis of the distribution of alleles of the gene NOS3 (T786C), affecting the synthesis of nitric oxide showed that polymorphic allele C 2 times more often detected in the group with MI and DN– 38,7%, compared to the comparison group 17,1%, p&amp;lt;0,05. T- allele was statistically more frequent in II-82,9% than in I-61,3%, p&amp;lt;0,05. Polymorphism (Leu28Pro) of the APOE gene, potentiating hyperlipoproteinemia, the Pro allele was more often detected in group I – 8,9%, than in group II – 1,3%, p&amp;lt;0,05. Analysis of allele expression features of the SLCO1B1 gene polymorphism (Val174Ala), which affects the metabolism of statins, did not revealed a significant difference between the groups, p&amp;gt;0,05. Polymorphic variants (G681A and Trp212Ter) of CYP2C19 gene, determining sensitivity to clopidogrel, had the following characteristics: allele *1 was more frequently detected in the control group – 96,7%, relative to the Ist – 88,7%, p&amp;lt;0,05. Allele *2 was leader in patients with MI and DN – 8,9%, compared to control 2,0%, p&amp;lt;0.05. Distribution of allele *3 between groups did not differ statistically in I – 2,4%, II – 1,3%, p&amp;gt;0,05. Clinical presentation of the long-term period (12 months): hospitalizations of patients due to decompensated chronic heart failure (CHF) in I – 19,1%, in II – 6,6%, p&amp;lt;0,05. Recurrences of acute coronary syndrome (ACS) met 3 times more often in group I – 15,5%, versus 5,3% in the second group, p&amp;lt;0,05. Stent thrombosis: 6 times more frequent in the group with MI and DN, compared to the control group of 1,3%, p&amp;lt;0,05. Long-term mortality: I – 15,5%, II – 4,0%, p&amp;lt;0,05. Conclusions In patients with MI and DN, polymorphic alleles of the NOS3, APOE, and CYP2C19 genes are statistically more common, which probably has an additional aggravating effect on the course of disease in the long-term period (1 year). In the group of patients with MI and DN, for a long-term period (1 year), it is statistically more often complicated by CHF decompensation, recurrent ACS, and stent thrombosis, which finally led to fatal outcomes with mortality rate 14,7%. Funding Acknowledgement Type of funding sources: None. Distribution of genetic variantsPresentation of the long-term period

Genetic variants in the p53 pathway influence implantation and pregnancy maintenance in IVF treatments using donor oocytes

PurposeSingle-nucleotide polymorphisms (SNPs) in the p53 pathways have shown to play a role in endometrial receptivity and implantation in infertile women undergoing in vitro fertilization (IVF). The present study aimed to assess the influence of these gene variants over pregnancy success through a receptivity model in recipients of egg donation treatments, when factors such as age and quality of the oocytes are standardized.MethodsA nested case–control study was performed on 234 female patients undergoing their first fresh IVF treatment as recipients of donor oocytes. Genotyping of TP53 Arg72Pro (rs1042522), LIF (rs929271), MDM4 (rs1563828), and USP7 (rs1529916) SNPs in the recipients allowed comparison of allele and genotype frequencies and their association with the IVF treatment outcome.ResultsGrouped by genotypes, patients showed differences in IVF outcomes after the embryo transfer. Arg72Pro (rs1042522) gene variant was associated to changes in implantation and clinical pregnancy rates. The polymorphisms USP7 (rs1529916) and MDM4 (rs1563828) were associated to differential ongoing pregnancy rates and variable miscarriage events, respectively.ConclusionsThis study highlights the association between gene polymorphisms related to P53 function and their influence over IVF reproductive outcomes. Arg72Pro variant may influence early events, as lower implantation rates were found in homozygous for Pro72 allele. By contrast, MDM4 (rs1563828) and USP7 (rs1529916) gene variants were associated with the later maintenance of pregnancy.

Allele expression of Peroxisome-gamma2 proliferation activator receptor gene in overweight eldery patients with ischemic heart disease

It is known that about a third of the world's population suffers from obesity. Peroxisome activation receptors, namely, the γ2 promoter, is abundantly locatein adipose tissue, regulating adipogenesis, lipid accumulation, and glucose homeostasis. The aim of this investigations was to study the expression features of the PPARγ2 gene alleles in elderly patients with comorbid conditions such as obesity and ischemic heart disease. From 2017 to 2019 in "Clinical Hospital № 29 named. N.E. Bauman” (Moscow) 140 patients of both sexes (54.3% men and 45.7% women) aged 60-89 years were examined by us. The main group included 70 pts with ischemic heart disease, and the control group included 70 pts without it. Pro12 allele carriage in the main group had 85%, and the Ala12 allele - 15%. Pro12Ala and Ala12Ala genotypes, Ala12 allele were detected more often in patients with ischemic heart disease than in the control group (p=0.0008 and p=0.0003, respectively). Pro12Ala genotypes carriage (OR=2.02, CI = 1.28-3.19, p=0.003) and Ala12Ala (OR=2.002, CI = 1.32-3.04, p=0.0006) of the Ala12 gene PPARγ2 increases the risk of developing ischemic heart disease by 2 times. The revealed features of the expression of PPARγ2 gene alleles in elderly patients with obesity and ischemic heart disease e confirm the ability of nuclear PPARs to control development, differentiation, metabolic homeostasis and reproduction. To clarify the role of various genotypes of the PPARy2 gene in the regulation of lipid metabolism and angiogenesis in the discussed comorbid conditions in elderly patients may help to identify new methods of it treatment.

Polymorphisms in P53 and VEGFA genes in different subtypes of periorbital hyperpigmentation

A black eye circle or periorbital hyperpigmentation affects men and women alike. The periocular area is affected by a poorly defined lesion that appears as round or semicircular brown or dark brown pigmented macules. VEGFA (rs833061) and P53 (rs1042522) polymorphisms were detected in various periorbital hyperpigmentation types. Methods: Thirty patients with periorbital hyperpigmentation were included in this prospective case-control research, along with twenty seemingly healthy control individuals of the same age and gender. The distribution of p53 and VEGFA genotypes in patients and controls did not vary significantly. Cases with POH were more likely to have p53 genotypes Pro/Pro and Arg/Pro+Pro/Pro than controls. A greater frequency of the VEGFA TC, CC, TC+CC genotypes, and the C allele were found in patients compared to the control group with POH risk. The VEGFA TC genotype was associated with the pigmented subtype. Periorbital hyperpigmentation was more likely to occur in those with the p53-pro/pro and arg/pro+pro/pro genotypes, the pro allele, VEGFA-TC, TC+CC, and C allele genotypes. There was a strong association between the VEGFA TC genotype and the pigment subtype. Otherwise. There was no relationship between VEGFA rs833061 and any of the VEGFA variants (p53 rs1042522 or p53 rs1042522). For orbital hyperpigmentation susceptibility, P53 and VEGFA genotypes have been proposed as risk factors.

In Vivo and In Vitro Study of the Genetic Effects of Cabergoline Drug

This study aimed to stand on genetic effects important of cabergoline drug. This toxic effect was evaluated for three different doses (0.05, 0.1, 0.5 mg/ml) in comparison with control (PBS/ phosphate buffer saline) both in vivo and in vitro. In vivo study involved the cytogenetic evaluation of cabergoline in mice by examination of mitotic index percentage (MI), micronucleus formation (MN) and chromosomal aberrations. Result indicated that all the tested doses cause significant reduction in MI percentage, while significant rise was seen with both MN formation and all studied chromosomal aberrations. While in vitro study involved measuring the effect of cabergoline on normal cell line (REF/ Rat embryonic fibroblast) by studing cell viability through MTT assay and a TP53 codon 72 polymorphism (rs1042522) through (PCR-RFLP). Results recorded that cabergoline caused high proliferation of normal cells at all doses and p53 polymorphism showed that the Arg allele yielding two fragments 213 and 140 bp after cleaving with BstuI,, while the Pro allele had a single 353 bp band because it did not cleaved by BstuI. In conclusion and according to the results care should be taken while obtaining cabergoline as a results of its genetic side effects.

Meta-analysis of the association between PPARγ2 gene Pro12Ala polymorphism and obesity in Chinese population

To explore the relationship between the peroxisome proliferator-activated receptor γ(PPARγ) 2 gene Pro12 Ala polymorphism and the risk of obesity in the Chinese population. Take "peroxisome proliferator activated receptor gamma2", "PPAR gamma2", "pparg2", "peroxisome proliferator-activated receptor gamma2", "obesity", "Pro12 Ala", "gene polymorphism", "Chinese" as searchable words, Chinese people were selected as study subjects from Chinese databases such as CNKI, Wanfang Database, VIP and foreign language databases such as PubMed, Embase, Cochrane Library and Web of Science, which were published from the establishment of the database until December 31, 2019. RevMan 5. 3 software was used for Meta-analysis of the literature with literature score ≥ 5 points. A total of 12 articles were included, including 2233 cases and 1795 healthy controls. Meta-analysis showed that:(1) Dominant gene model: the risk of obesity for those carrying Ala/Ala+Pro/Ala was 1. 86 times that of those carrying Pro/Pro(OR=1. 86, 95%CI 1. 07-3. 21). (2) Additive gene model: the risk of obesity for those carrying Pro/Ala was 1. 79 times that of those carrying Pro/Pro(OR=1. 79, 95% CI 1. 04-3. 08). (3) Allelic model: the risk of obesity in those carrying the allele Ala was 1. 75 times that of those carrying the allele Pro(OR=1. 75, 95% CI 1. 11-2. 78). The subgroup analysis of different regions showed that the combined OR(95% CI) values of the dominant gene model, additive gene model and allelic model in the southern region were 1. 96(1. 12-3. 42), 2. 02(1. 14-3. 56) and 1. 79(1. 06-3. 03), the combined OR(95% CI) values of the dominant gene model, additive gene model and allele model in the northern region were 1. 89(0. 90-3. 97), 1. 77(0. 85-3. 67) and 1. 80(0. 97-3. 36). The polymorphic allele Ala or genotype Ala/Ala or Pro/Ala of PPARγ2 gene may increase the risk of obesity in Chinese population. The correlation between the PPARγ2 gene Pro12 Ala polymorphism and the risk of obesity in the southern population is more obvious.

Human glutathione peroxidase codon 198 variant increases nasopharyngeal carcinoma risk and progression.

Glutathione peroxidase 1 (GPx-1) is a selenium-dependent detoxifying enzyme involved in the protection of cells against oxidative damage. Some genetic association studies reported significant associations between GPx-1 Pro198Leu variant and carcinogenesis across different populations; however, the impact of this variant on nasopharyngeal carcinoma (NPC) has not been explored. Therefore, the present study was planned to evaluate the potential involvement of the GPx-1 Pro198Leu variant and plasma GPx activity in the risk of developing NPC in a Tunisian population. The GPx-1 Pro198Leu genotype was determined in 327 NPC patients and 150 healthy controls by the RFLP-PCR analysis. The correlation between the GPx-1 variant and the clinicopathological parameters was examined. GPx activity was assessed in the plasma of 119 NPC patients and 58 healthy control subjects and according to GPx-1 genotypes and clinicopathological characteristics of NPC patients. A significant association was found between GPx-1 Pro198Leu variant and NPC risk in a Tunisian population. The allelic frequencies of Pro and Leu alleles were 32% versus 68% and 41% versus 59% in NPC cases and controls, respectively. Thus, the minor 198 Leu allele increased significantly in NPC patients and appeared as a potential risk factor for NPC occurrence (OR = 1.48, CI 95% = 1.14-1.91, p = 0.002). The plasma GPx activity was significantly higher in NPC patients than in controls (p = 0.03). According to the clinicopathological characteristics of NPC patients, GPx activity decreased significantly in patients with lymph node metastasis (p = 0.004). This is the first study showing a strong association between GPx-1 Pro198Leu genetic variant and NPC risk. GPx-1 Pro198Leu variant increased the development of regional lymph node metastasis. Plasma GPx activity was higher in NPC patients. Thus, GPx-1 gene could be considered as a determinant factor influencing NPC risk and progression.

Associations of TP53 codon 72 polymorphism with complications and comorbidities in patients with type 1 diabetes

Wild-type TP53 plays an important role in the regulation of immune response and systemic inflammation. In type 1 diabetes (T1D), TP53 pathways are upregulated and an increased susceptibility to apoptosis is observed. We hypothesize that TP53 codon 72 polymorphism could be associated with complications and comorbidities in patients with T1D. We have investigated the associations of the TP53 codon 72 polymorphism with the T1D complications and comorbidities (retinopathy, nephropathy, hypertension, dyslipidemia, autoimmune thyroiditis, and celiac disease) in 350 patients. The key results of our approach are as follows: (1) In diabetic subjects, the Pro/Pro genotype is associated with an increased risk of microvascular complications, dyslipidemia, and celiac disease; (2) the Arg/Arg variant is associated with a decreased risk of autoimmune thyroiditis and celiac disease; (3) the Pro allele is associated with an increased risk of dyslipidemia, autoimmune thyroiditis, and celiac disease. Although further studies are required, our results for the first time indicate that the TP53 codon 72 polymorphism could be considered a genetic marker to predict the increased susceptibility to some T1D complications and comorbidities.Key messagesWe analyzed the TP53 codon 72 polymorphism in patients with T1D.Pro/Pro genotype is associated with an increased risk of microvascular complications, dyslipidemia, and celiac disease.The Arg/Arg variant is associated with a decreased risk of autoimmune thyroiditis and celiac disease.The Pro allele is associated with an increased risk of dyslipidemia, autoimmune thyroiditis, and celiac disease.

P.Arg72Pro polymorphism of P53 and breast cancer risk: a meta-analysis of case-control studies

BackgroundThe effect of the p.Arg72Pro variant of the P53 gene on the risk of development ofbreast cancer remains variable in populations. However, the use ofstrategies such aspoolingage-matched controls with disease may provide a consistent meta-analysis. Our goal was to perform a meta-analysis in order to assess the association of p.Arg72Pro variant of P53 gene with the risk of breast cancer.MethodsDatabases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Case-control studies with age-matched on breast cancer havingevaluated the genotype frequencies of the TP53 p.Arg72Pro polymorphism were selected. The fixed and random effects (Mantel-Haenszel) were calculated using pooled odds ratio of 95% CI to determine the risk of disease. Inconsistency was calculated to determine heterogeneity among the studies. The publication bias was estimated using the funnel plot.ResultsTwenty-one publications with 7841 cases and 8876 controls were evaluated in this meta-analysis. Overall, our results suggested that TP53 p.Arg72Pro was associated with the risk of breast cancer for the dominant model (OR = 1.09, 95% CI = 1.02–1.16, P = 0.01) and the additive model (OR = 1.09, 95% CI = 1.01–1.17, P = 0.03), but not for the recessive model (OR = 1.07, 95% CI = 0.97–1.18, P = 0.19). According to the ethnic group analysis, Pro allele was associated with the risk of breast cancer in Caucasians for the dominant model and additive model (P = 0.02), and Africans for the recessive model and additive model (P = 0.03).ConclusionsThis meta-analysis found a significant association between TP53 p.Arg72Pro polymorphism and the risk of breast cancer. Individuals carrying at least one Pro allele were more likely to have breast cancer than individuals harboring the Arg allele.

Study the Role of Tp53 in the Development of Hepatocellular Carcinoma in HCV Infected Patients

Background: Hepatocellular carcinoma (HCC) is considered as the primary malignancy of the liver that usually occurs on top of chronic viral hepatitis. The TP53 (tumor protein 53) is a tumor suppressor gene which is the 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. Objectives: to determine the association of the TP53 Arg72Pro polymorphism with the risk of HCC development in Hepatitis C virus (HCV) infected Egyptian patients. Methodology: This is a case control study conducted in Sohag University Hospital on 100 participants (20 HCC, 20 CHCV, 40 LC and 20 control). TP53 gene polymorphism was identified by Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP), serum level of TP53 was measured by quantitative ELISA. Results: The GG genotype / G allele has the highest frequency in the controls, while the CC genotype/ C allele was more frequently found in the HCC patients. Carriage of TP53 CC genotype and TP53 serum level have a statistical significant association with HCC development. Conclusion: the CC genotype and the Pro (C) allele of TP53, codon 72 are risk factors for HCC in patients infected with HCV and the serum TP53 level is overexpressed in HCC patients.

Association of Molecular Genetic Markers of TP53, MDM2, and CDKN1A Genes with Progression-Free Survival of Patients with Ovarian Cancer after Platinum-Based Chemotherapy.

We studied the association of polymorphic markers of cell cycle control genes (Arg72Pro of the TP53 gene, T(-410)G of the MDM2 gene, and Ser31Arg of the CDKN1A gene) in ovarian cancer and progression-free survival following platinum-based chemotherapy. Tumor tissue samples obtained from 49 patients who had undergone chemotherapy were examined. Patients received standard platinum-based chemotherapy and were observed until disease progression. Polymorphic markers of genes were evaluated by PCR-RFLP and real-time PCR. In patients carrying the G allele of the T(-410)G marker of the MDM2 gene, a decreasing trend was observed in median progression-free survival. An increase in the median progression-free survival was observed in carriers of the Pro allele of the TP53 gene (p=0.045). Furthermore, a stronger association was noted with carriers of the minor Pro/Pro homozygous genotype relative to the Arg/Arg genotype (p=0.007). In the subgroup of patients who underwent optimal or complete cytoreductive surgery, carriage of the minor Arg allele of the Ser31Arg marker (CDN1A gene) was associated with a decrease in the median progression-free survival time (p=0.004).

Association of TP53 Codon 72 Arg>Pro Polymorphism with Breast and Lung Cancer Risk in the South Asian Population: A Meta-Analysis.

Background:A transversion missense polymorphism of the TP53 tumor suppressor gene at the codon 72 codes proline instead of arginine causes an altered p53 protein expression and has been found to be associated with an elevated risk of various cancer; especially breast and lung cancer. As the previous case-control studies on the South Asian population have shown controversial results, we performed a meta-analysis to evaluate a precise estimation of the relationship between the TP53 Arg72Pro polymorphism with breast and lung cancer. Methods:A total of 12 related studies on the South Asian population have been included through comprehensive database searching. Six studies were selected for breast cancer meta-analysis involving 950 cases and 882 controls; the other six studies were for lung cancer meta-analysis including 975 cases and 1397 controls. The results have been determined by using the Review Manager (RevMan) 5.3. Additionally, the stability of our analysis was assessed by heterogeneity, publication bias analysis and sensitivity testing. Results:A significantly increased risk of breast cancer was found in Pro allele (Pro vs. Arg), co-dominant model 2 (Pro/Pro vs. Arg/Arg), dominant model (Pro/Pro + Arg/Pro vs. Arg/Arg). In case of lung cancer, significantly increased risk was found in the allele, co-dominant 1, co-dominant 2, co-dominant 3, dominant, and recessive models. No association with other genetic models with breast and lung cancer risk was found in the South Asian population. Conclusions:Our results indicate that TP53 Arg72Pro polymorphism is a risk factor for the development of breast cancer and lung cancer in the South Asian population.