P53 Polymorphism Research Articles

Association of Glutathione Transferase M1, T1, P1 and A1 Gene Polymorphism and Susceptibility to IgA Vasculitis.

Endothelial cell injury is a hallmark of IgA vasculitis (IgAV), possibly associated with various factors, including oxidative stress. Certain single nucleotide polymorphisms (SNPs) of glutathione S-transferases (GST) genes have been shown to increase susceptibility to oxidative stress. The objective of our study was to evaluate the gene polymorphisms of GSTM1, GSTT1, GSTP1, and GSTA1 in patients with IgAV. DNA was extracted from the blood of 124 children with IgAV and 168 age-matched healthy controls. A higher frequency of the GSTM1 null genotype was observed in patients with gastrointestinal (GI) system involvement compared to those without GI system involvement (51.5% vs. 28.6%, p = 0.011). Additionally, the GSTM1 null genotype was less prevalent (30.8% vs. 69.2%, p = 0.032), while the GSTP1 Val/Val genotype was significantly more prevalent in patients who developed urogenital complications (scrotal swelling) during the course of the disease (60% vs. 40%, p = 0.039). This study is the first to suggest an association between GSTM1 and GSTP1 polymorphisms and various phenotypes observed during the clinical course of IgAV in the pediatric population. However, it was performed on a national and likely single ethnic cohort, too small for definitive conclusions, so larger studies are needed to confirm this association.

Abstract PO3-15-02: TP53 GENE POLYMORPHISM AT CODON 72 AS A RESPONSE PREDICTOR FOR NEOADJUVANT CHEMOTHERAPY

Abstract Introduction: Breast cancer is one of the most prevalent in women in the world and has shown extensive changes in treatment in recent decades. More patients are undergoing neoadjuvant chemotherapy in order to achieve pathological complete response (CPR) and perform less aggressive surgeries. CPR increases overall and disease-free survival and the decrease in tumor size increases the chances of conservative surgery. We have numerous studies that propose to discover CPR markers. Predictive factors of response to chemotherapy are important for treatment planning and the P53 gene, apoptosis-inducing gene, plays a role in inducing response to chemotherapy drugs that act by inducing apoptosis. The presence of mutations and genetic polymorphisms act by modulating this response. Among these, the codon 72 polymorphism is one of the most studied, as its polymorphic variants Arg/Arg, Arg/Pro and Pro/Pro encode a p53 with different functioning at the cell level. So, individuals with different polymorphisms will have different apoptotic action and different response to chemotherapy treatments. Objectives: Based on this knowledge, the study sought to correlate the polymorphism variants at codon 72 with the complete pathological response to neoadjuvant chemotherapy. Casuistic and Methods: The study was carried out at an oncology center in the state of Sergipe, in northeastern Brazil. A total of 206 patients with breast cancer who underwent neoadjuvant chemotherapy and core needle biopsy of the breast at the beginning of treatment were included in the stud,in the period from 2019 to 2022. From these patients, oral swab samples were collected for PCR evaluation of the P53 polymorphism at codon 72. The polymorphisms were studied using the Sanger technique at the Sao Paulo School of Medicine of the Federal University of São Paulo (UNIFESP). Patients were prospectively evaluated after surgery to verify the surgical pathological response after chemotherapy. Pathologic response was assessed using the RECIST criteria. The study was evaluated and approved by the ethics and research committee of UNIFESP and all patients signed an informed consent form. Results: Of the 206, 18.4% met the exclusion criteria (did not undergo surgery, interrupted chemotherapy treatment, insufficient genetic material in the swab, loss of follow-up). Of the 168 patients analyzed, 44.6% were Arg/Arg, 17.3% Pro/Pro and 38.0% Arg/Pro. Complete pathological response (PCR) was obtained in 21.4% of the patients, 10.1% had progressive disease (PD), 13.7% had stable disease (SD) and 54.2% had partial pathological response (PPR). Of the patients who achieved RPC, 47.2% were Arg/Arg, 38.9% Arg/Pro and 13.9% Pro/Pro without statistical significance, among the variants of polymorphisms. The only predictor of CPR in multivariate regression was immunohistochemistry (p< 0.001). The only predictor of CPR in multivariate regression was immunohistochemistry (p< 0.001) Conclusion: The P53 polymorphism at codon 72 is not a predictor of complete pathological response, but the Arg/Pro and Pro/Pro polymorphisms increase the chances of stable disease after neoadjuvant chemotherapy. Citation Format: Jussane Vieira, Afonso Nazário, João Pesquero. TP53 GENE POLYMORPHISM AT CODON 72 AS A RESPONSE PREDICTOR FOR NEOADJUVANT CHEMOTHERAPY [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-15-02.

Glutathione S-transferase M1, T1, and P1 polymorphisms and periodontitis in a Caucasian population: a case-control study

BackgroundGlutathione S-transferases (GSTs) play important roles in protecting cells against oxidative stress and toxic chemicals. This study aimed to investigate the distribution of GSTM1, GSTT1, and GSTP1 variants and their roles in periodontitis susceptibility in a Caucasian population.MethodsWe analyzed 406 participants, including 204 healthy controls and 203 periodontitis patients. A multiplex polymerase chain reaction (PCR) approach was used to analyze GSTM1 and GSTT1 loci. GSTP1 variants were detected by PCR-haplotyping method in a subgroup of participants (N = 350). Chi-square or Fisher´s exact tests were used to compare genotypic and allelic differences. The Bonferroni method was applied to correct for multiple comparisons (pcorr).ResultsThe GSTM1 genotype distribution did not differ significantly between controls and periodontitis patients (p = 0.44). Additionally, the wild/null genotypes of GSTT1, Ile105Val and Ala114Val frequencies of GSTP1 were not significantly different between the two groups after correction for multiple comparisons (p = 0.05, p = 0.55, p = 0.02, pcorr>0.05, respectively). The GSTM1 and GSTP1 Ile105Val gene variants were similarly distributed between non-smokers and smokers in both groups (p = 0.38, p = 0.20, and p = 0.14, p = 0.35, respectively). However, the wild genotype of the GSTT1 and Ala114Ala variant of the GSTP1 genes were present more frequently in non-smoking periodontitis patients than in non-smoking controls (p = 0.03, pcorr>0.05, and p = 0.009, pcorr>0.05, respectively) although their frequencies did not differ between smoking periodontitis patients and smoking controls (p = 0.23, p = 0.68, respectively).ConclusionsThis study in a Czech Caucasian population did not confirm a highly significant association between GST gene variants and susceptibility to periodontitis, as previously reported by Arshad and colleagues in Pakistanis. However, a weak relationship between GSTT1 and GSTP1 rs1138272 polymorphisms and periodontitis in non-smokers was observed.

Adipocyte p53 coordinates the response to intermittent fasting by regulating adipose tissue immune cell landscape

In obesity, sustained adipose tissue (AT) inflammation constitutes a cellular memory that limits the effectiveness of weight loss interventions. Yet, the impact of fasting regimens on the regulation of AT immune infiltration is still elusive. Here we show that intermittent fasting (IF) exacerbates the lipid-associated macrophage (LAM) inflammatory phenotype of visceral AT in obese mice. Importantly, this increase in LAM abundance is strongly p53 dependent and partly mediated by p53-driven adipocyte apoptosis. Adipocyte-specific deletion of p53 prevents LAM accumulation during IF, increases the catabolic state of adipocytes, and enhances systemic metabolic flexibility and insulin sensitivity. Finally, in cohorts of obese/diabetic patients, we describe a p53 polymorphism that links to efficacy of a fasting-mimicking diet and that the expression of p53 and TREM2 in AT negatively correlates with maintaining weight loss after bariatric surgery. Overall, our results demonstrate that p53 signalling in adipocytes dictates LAM accumulation in AT under IF and modulates fasting effectiveness in mice and humans.

Unveiling the etiological impact of GST-M1, GST-T1, and P53 genotypic variations on brain carcinogenesis.

Functional variants of glutathione-S-transferase (GST)-M1, GST-T1, p53 might modulate brain cancer risk by altering the rate of metabolism and clearance of carcinogens from the brain tissue. In this study, the role of GST-M1, GST-T1, p53 polymorphisms on brain tumor was investigated. Brain tumor tissues of 143 patients were obtained from the Gulhane Training and Research Hospital, Department of Neurosurgery between 2019 and 2020. In the xenobiotic mechanism, the null allele frequency in the GST-T1, GST-M1 gene regions of Phase II enzymes by qPCR method were investigated. Single nucleotide polymorphism encoding Arg/Pro conversion in the p53 gene region was analyzed in 120 cases by sequence analysis method. The data were analyzed statistically with patient's demographic and clinical data. GST-M1, GST-T1, p53 genotypes of the patient group were determined. The most frequent genotype was null genotype (0/0) for GST-M1 (χ2 = 39.756, p < 0.001). GST-M1 genotype frequencies were 30.8%, 23.1%, 44.3% for 1/1, 1/0, 0/0, respectively. The most frequent genotype was GST-T1 1/1 following by GST-T1 1/0 (χ2 = 0.335, p = 0.846). GST-T1 genotype frequencies were 64.3%, 30.8%, 4.9% for 1/1, 1/0, 0/0, respectively. GST-M1 null genotype might be associated with the development of brain tumors. Genotype distribution obtained in p53 exon 4 codon 72; Arg/Arg was determined as 31 (25.8%), Arg/Pro 70 (58.3%), and Pro/Pro 19 (15.8%) in the case group, while there were 18 (38.3%), 23 (48.9%), and 6 (12.8%) respectively in the control group. However, the genotype distribution of p53 exon 4 codon 72 among tumorous tissue did not significantly vary from healthy control tissues (χ²=2.536, p = 0.281). The null allele frequency encountered in the GST-M1, GST-T1 gene regions is consistent with the rates in the gene pool called Caucasian in the literature. GST-M1 gene polymorphism may play a crucial role in brain carcinogenesis in Turkish patients. This study based on clinical data is thought to help to understand the important epidemiological features of brain tumors.

TP53 and p21 (CDKN1A) polymorphisms and the risk of systemic lupus erythematosus

BackgroundThe p53 and p21 proteins are important regulators of cell cycle and apoptosis and may contribute to autoimmune diseases, such as systemic lupus erythematosus (SLE). As genetic polymorphisms may cause changes in protein levels and functions, we investigated associations of TP53 and p21 (CDKN1A) polymorphisms (p53 72 G > C—rs1042522; p53 PIN3—rs17878362; p21 31 C > A—rs1801270; p21 70 C > T—rs1059234) with the development of systemic lupus erythematosus (SLE) in a Southeastern Brazilian population.MethodsGenotyping of 353 female volunteers (cases, n = 145; controls, n = 208) was performed by polymerase chain reaction, restriction fragment length polymorphism and/or DNA sequencing. Associations between TP53 and p21 polymorphisms and SLE susceptibility and clinical manifestations of SLE patients were assessed by logistic regression analysis.ResultsProtective effect was observed for the genotype combinations p53 PIN3 A1/A1-p21 31 C/A, in the total study population (OR 0.45), and p53 PIN3 A1/A2-p21 31 C/C, in non-white women (OR 0.28). In Whites, p53 72 C-containing (OR 3.06) and p53 PIN3 A2-containing (OR 6.93) genotypes were associated with SLE risk, and higher OR value was observed for the combined genotype p53 72 G/C-p53 PIN3 A1/A2 (OR 9.00). Further, p53 PIN3 A1/A2 genotype was associated with serositis (OR 2.82), while p53 PIN3 A2/A2 and p53 72 C/C genotypes were associated with neurological disorders (OR 4.69 and OR 3.34, respectively).ConclusionsOur findings showed that the TP53 and p21 polymorphisms included in this study may have potential to emerge as SLE susceptibility markers for specific groups of patients. Significant interactions of the TP53 polymorphisms with serositis and neurological disorders were also observed in SLE patients.

TP53 (rs1042522, rs28934571) and TP21 (rs1801270, rs1059234) Polymorphisms and Risk of Breast Cancer among Rural Women of Maharashtra: Findings from a Hospital Based Case- Control Study.

Various studies all around the world depicted the relationship of polymorphisms in tumor suppressor genes with risk of various cancers, but there are unambiguous conclusions on this association. A hospital based case-control study was designed to review the association of polymorphism of tumor suppressor genes p21 and p53 with breast cancer risk in women residing in rural Maharashtra. Two single nucleotide polymorphisms (SNPs) a C>A transversion (Ser>Arg) at codon 31 of exon 2 (rs1801270), C>T transition occurring 20bp upstream from stop codon of exon 3 (rs1059234) in p21 gene and G>C (Arg>Pro) transition at codon 72 of exon 4 (rs1042522), G>T (Arg>Ser) transition at codon 249 in exon 7 (rs28934571) in p53 gene were studied. To precise the quantitative assessment, we enrolled 800 subjects sorted into 400 clinically confirmed breast cancer patients and 400 healthy women from a tertiary care hospital (Krishna Hospital and Medical Research Centre) of south-western Maharashtra. The genetic polymorphisms in p21 and p53 genes was studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method using blood genomic DNA isolated from breast cancer patients and controls. The level of association of polymorphisms was assessed using Odds ratio (OR) with 95% confidence interval and p-value identified using logistic regression model. After the analysis of SNPs (rs1801270, rs1059234) of p21 and (rs1042522, rs28934571) in p53 gene our analysis suggested that heterozygote Ser/Arg genotype with OR=0.66; 95% CI: 0.47- 0.91; p=0.0003 and homozygote variant Arg/Arg genotype with OR=0.23; 95% CI: 0.13- 0.40; p<0.0001of rs1801270 of p21 was negatively associated with risk of breast cancer in studied population. The findings from this study supported that rs1801270 SNP of p21 was inversely associated with breast cancer risk in the studied rural women population.

Association of Interactions between Metabolic 'Caretaker' Genes, p53, MDM2, and Tobacco Use with the Risk of Oral Cancer: A Multifactor Dimensionality Reduction Approach.

The present study investigated the association of interactions between gene polymorphisms in metabolic 'caretaker' genes (Phase I: CYP1A1, CYP2E1; Phase II: GSTM1, GSTT1), the cell cycle regulatory gene, p53, along with its negative controller, MDM-2, and the environment variable (tobacco). A nonparametric model, multifactor dimensionality reduction (MDR), was applied to analyse these interactions. This case-control study was carried out on 242 subjects. Genomic DNA was extracted from peripheral blood lymphocytes.11 gene variants with an exposure variable (tobacco use) were analysed using MDR to identify the best locus model for gene-gene and gene-environment interactions. Statistical significance was evaluated using a 1000-fold permutation test using MDR permutation testing software (version 1.0 beta 2). The value of p<0.05 was considered statistically significant. The best three-locus model for gene-gene interaction included two of the p53 gene polymorphisms; rs17878362 (intron 3) and rs1042522 (exon 4) and rs6413432 in the Phase I gene, CYP2E1(DraI). The three-locus model to evaluate the gene-environment interaction included two intronic polymorphisms of the p53 gene, that is, rs17878362 (intron 3) and rs1625895 (intron 6), and rs4646903 in the Phase I gene CYP1A1*2C. The interaction graphs revealed independent main effects of the tobacco and p53 polymorphism, rs1042522 (exon 4), and a significant additive interaction effect between rs17878362 (intron 3) and rs1042522 (exon 4). The nonparametric approach highlighted the potential role of tobacco use and variations in the p53 gene as significant contributors to oral cancer risk. The findings of the present study will help implement preventive strategies in both tobacco use and screening using a molecular pathology approach.

Targeting PSAT1 to mitigate metastasis in tumors with p53-72Pro variant

The single-nucleotide polymorphism (SNP) of p53, in particular the codon 72 variants, has recently been implicated as a critical regulator in tumor progression. However, the underlying mechanism remains elusive. Here we found that cancer cells carrying codon 72-Pro variant of p53 showed impaired metastatic potential upon serine supplementation. Proteome-wide mapping of p53-interacting proteins uncovered a specific interaction of the codon 72 proline variant (but not p5372R) with phosphoserine aminotransferase 1 (PSAT1). Interestingly, p5372P-PSAT1 interaction resulted in dissociation of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) that otherwise bound to p5372P, leading to subsequent nuclear translocation of PGC-1α and activation of oxidative phosphorylation (OXPHOS) and tricarboxylic acid (TCA) cycle. Depletion of PSAT1 restored p5372P-PGC-1α interaction and impeded the OXPHOS and TCA function, resulting in mitochondrial dysfunction and metastasis suppression. Notably, pharmacological targeting the PSAT1-p5372P interaction by aminooxyacetic acid (AOA) crippled the growth of liver cancer cells carrying the p5372P variant in both in vitro and patient-derived xenograft models. Moreover, AOA plus regorafenib, an FDA-proved drug for hepatocellular carcinoma and colorectal cancer, achieved a better anti-tumor effect on tumors carrying the p5372P variant. Therefore, our findings identified a gain of function of the p5372P variant on mitochondrial function and provided a promising precision strategy to treat tumors vulnerable to p5372P-PSAT1 perturbation.

Artificial Intelligence Based Study Association between p53 Gene Polymorphism and Endometriosis: A Systematic Review and Meta-analysis.

The P53 gene is critical to the onset and progression of cancers. Currently, relevant study findings indicate that the p53 gene may have a strong association with the risk of endometriosis, but these findings have not been united. To gather more statistically meaningful clinical data, we used meta-analysis to examine the relationship between the rs1042522 single nucleotide polymorphism of the tumor suppressor gene p53 and the incidence of endometriosis. Through a comprehensive literature survey of PubMed, MEDLINE, EMBASE, Springer, and Web of Science literature databases, we obtained a clinical control case study on the relationship between p53 gene polymorphism and the prevalence of female endometriosis and finally traced the relevant references included. The quality of the literature included in this study was evaluated, and Revman5.3 was used to complete the meta-analysis. This research includes eight publications. The total number of cases in the study group was 1551, whereas the total number of cases in the control group was 1440. The findings of the sensitivity analyses of each omitted piece of the literature revealed no significant difference. The results of the meta-analysis showed that there were significant differences in the GG gene frequency (OR = 0.56, 95%CI (0.38, 0.92), P = 0.003), allele G (OR = 2.46, 95%CI (1.41,4.29), P = 0.002), and allele C (OR = 0.62, 95%CI (0.46, 0.84), P = 0.002) between the study group and the control group (P < 0.01), but there was no significant difference in the GC gene frequency (OR = 1.17, 95%CI (1.01,1.36), P = 0.03), and the CC gene frequency (OR = 1.25, 95%CI (0.85,1.82), P = 0.26) (P > 0.01). Our study results show that there is a significant correlation between the single nucleotide of the p53 gene and the incidence rate of female endometriosis, in which the decrease of the GG gene frequency and the increase of allele C are likely to increase the risk of such diseases.

Alterations in p53 Influence hTERT, VEGF and MMPs Expression in Oral Cancer Patients.

Mutant p53 is the crucial molecule in the etiopathogenesis of oral cancer. Therefore, we aimed to evaluate the impact of alterations of the p53 gene and its negative feedback regulator, MDM2, on the expression of hTERT, VEGF, and MMPs; the critical genes involved in oral cancer progression. p53 and MDM2 genotyping were done by PCR-RFLP. p53 mutation analysis was performed using PCR-SSCP and sequencing. hTERT, VEGFA isoforms, MMP2, and MMP9 mRNA levels were analyzed by semi-quantitative Reverse Transcriptase PCR. Arg allele at p53 exon 4 was significantly associated with overexpression of hTERT, MMP2, and MMP9 individually. Expression of hTERT, VEGF A isoforms, MMP2 and MMP9 were significantly altered in the presence of p53 and MDM2 polymorphisms and p53 mutations in a specific combination. Mutant p53, Arg allele at p53 exon 4 locus, and G/G/or T/T genotype at MDM2revealed increased expression of hTERT, VEGF A isoforms, and MMP2/9. This study provides evidence that apart from mutant p53, naturally occurring sequence variants in p53codon 72 (Arg72Pro) (rs1042522) and MDM2 (rs2279744) significantly alter the expression of hTERT, VEGF-A isoforms, and MMP2/9 in a specific combination. The differential interaction of codon 72 variants with MDM2, hTERT, VEGF-A isoforms and MMP2/9 play a role in the aggressiveness of oral cancer. The results have important implications for oral cancer progression and should be explored for innovative treatment options.

P53 Polymorphism in Oral Lichen Planus

Oral lichen planus (OLP) is a chronic relapsing inflammatory disease. It involves T-lymphocyte aggression targeted to the basal layer of the oral mucosa.p53 plays a central role in the prevention of normal cells from the development of the malignant phenotype. Somatic alterations in p53 cause defects in normal p53 function. Wild type p53 plays an important role in repairable damage of the cell due to cellular stresses. Over-expression, as well as polymorphic variants of Mouse double minute 2(MDM2), have effects on p53 disturbances. In addition, degradation of p53 by E6 protein of high-risk human papillomavirus is also suggested as one of the mechanisms which attenuate p53 responses in oral carcinogenesis. Polymorphisms in p53 are anticipated to cause measurable disturbance in p53 function. Polymorphism of the codon 72 on exon 4 of the gene p53 is the first and most commonly known polymorphism of this gene. The presence of p53 has been demonstrated as an early marker of dysplasia in Oral Potentially Malignant Disorders. This review discusses about p53 polymorphism as an early indicator of genetic predisposition to neoplastic transformation in OLP.

Serum Derivatives of Reactive Oxygen Metabolites are Associated with Severity of Chronic Obstructive Pulmonary Disease and Affected by a p53 Gene Polymorphism.

PurposeOxidative stress is known to activate tumor suppressor p53, which inhibits cell cycle progression and induces apoptosis. Levels of p53 in lung tissues from patients with chronic obstructive pulmonary disease (COPD) are increased compared with levels in nonsmokers or smokers without emphysema. A polymorphism in p53 codon 72 (rs1042522) is associated with emphysematous changes in patients with COPD. However, whether oxidative stress in the serum is associated with the p53 polymorphism and disease severity in COPD patients is unclear.Patients and MethodsA total of 251 patients with a history of smoking more than 10 pack-years were enrolled in this study, and serum levels of derivatives of reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), and d-ROMs/BAP ratio (oxidative stress index; OSI) were measured. The percent low-attenuation area (LAA%) and cross-sectional area of the erector spinae muscles (ESMCSA) at the Th12 level were calculated from chest high-resolution computed tomography images. p53 codon 72 C/G genotyping was performed using polymerase chain reaction–restriction fragment length polymorphism analysis.ResultsIn patients carrying the p53 GG genotype, LAA% was significantly higher than in those carrying the CC genotype. d-ROM levels and OSI were associated with COPD severity and correlated with airflow limitation and markers of muscle atrophy (ESMCSA and creatinine/cystatin C ratio). Associations between markers of oxidative stress and COPD severity were observed primarily in patients carrying the p53 codon 72 GG genotype.ConclusionSusceptibility to pulmonary emphysema and responses to oxidative stress may be affected by the p53 gene polymorphism.

Miyelodisplastik sendrom hastalığında P53 polimorfizmlerinin önemi

Amaç: Miyelodisplastik sendrom (MDS) akut miyeloid lösemiye dönüşüm riski yüksek olan, artmış apoptozis ve azalmış hematopoez oranlarıyla karakterize klonal bir hastalıktır. MDS patogenezi tam olarak açıklanabilmiş değildir. Olguların ~%50' si anormal karyotiptedir ve bu oran ikincil MDS' de %80 civarındadır. P53 proteini kök hücre homeostazının önemli düzenleyicisidir ve hücre döngüsünün düzenlenmesi, apoptotik ile enflamatuar yanıt gibi bir dizi hücresel olayda yer alır. Genomik bütünlüğün korunmasında da önemli görevleri bulunan TP53 geni kanserlerde sıklıkla mutasyona uğramaktadır; ancak, mutasyonlarının yanında bazı gen polimorfizmlerinin de kanserle ilişkili oldukları bilinmektedir. Çalışmadaki amacımız, dört yaygın p53 tek nükleotid polimorfizminin MDS’ deki yaygınlıklarını ve hastalık gelişimi üzerine etkilerini belirlemektir. Bu amaçla, Ege Üniversitesi Tıp Fakültesi Dahiliye Anabilim Dalı Hematoloji Bilim Dalı' nda MDS tanısı ile takip edilen ya da yeni tanı almış 100 olgu çalışmaya dahil edildi. Gereç ve Yöntem: MDS’li olguların periferik kan lökositlerinden izole edilen DNA’lar gerçek-zamanlı PCR yöntemiyle çalışılarak, p53 polimorfizmleri (rs35163653, rs35993958, rs1800371, rs1042522) uygun probların kullanımıyla ve erime eğrisi analizleriyle belirlendi. Bulgular: İncelenen dört yaygın p53 polimorfizmin arasında özellikle rs1042522 polimorfizmindeki atasal olmayan G alelinin MDS’li olgularda artmış olduğu gözlenmiştir (C:%30.3; G:%69.7). Fonksiyonel olduğu, yani sentez edilen proteinin fonksiyonunu etkilediği bilinen bu polimorfizmde 417. pozisyonundaki C nukleotidinin G’ye transisyonu (C&amp;gt;G), proteinin 72. pozisyonundaki prolin amino asidinin arjinine (P72R) kodlanmasına yol açmaktadır. Sonuç: Çalışmamız, MDS hastalık grubunda rs35163653, rs35993958, rs1800371 ve rs1042522 p53 polimorfizmlerinin araştırıldığı ilk çalışmadır. Bunlardan, rs1042522 polimorfizminin kansere yatkınlık ve duyarlılıkla ilişkili olduğu yapılan diğer bazı çalışmalarla gösterilmiş olması nedeniyle, MDS hastalığı için de yüksek risk oluşturabileceği düşünülmektedir. Sonuç olarak, MDS hastalığı için gerçekleştirilen bu çalışmanın daha geniş bir olgu grubuyla tekrarlanmasıyla rs1042522 polimorfizmi ileride MDS teşhisinde belirteç olarak kullanılabilecektir.

Association between miR-196a-2 Gene Polymorphism and Ovarian Cancer Prognosis in Egyptian Females.

Background:Ovarian cancer is the fifth leading cause of cancer-related deaths among women worldwide. Unfortunately, early detection tests are relatively lacking. Diagnosis in the late stages of the disease carries a poor prognosis. Objective:To evaluate the relationship between miR-196a-2 rs11614913 polymorphism and ovarian cancer risk and prognosis in Egyptian females. Methods: In this case-control study, the participants were classified into 2 groups. Group A is the control group which included 50 healthy females. Group B included 50 patients newly diagnosed with ovarian carcinoma confirmed by histopathological analysis. Immunohistochemistry for P53 and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for miR-196a-2 genotypes detection were performed. Results:There was a statistically significant difference among ovarian cancer cases and controls regarding genotypes (P = 0.003). However, the distribution of the T and C alleles in both studied groups showed no significant difference (P = 0.17). There was a statistically significant increase of CA 125 levels among CT and CC genotypes carriers of ovarian cancer cases (p = 0.04). Besides, there was a statistically significant correlation between miR-196a-2 polymorphism and each of tumor grade (P <0.001), p53 immunohistochemical expression (P= 0.002), and Figo classification (P <0.001). Conclusion:There was a statistically significant increase of CA 125 levels among C allele carriers of ovarian cancer cases. Besides, there was a statistically significant association between the miR-196a-2 polymorphism and each of tumor grade, p53 immunohistochemical expression, and Figo classification. So, miR-196a-2 polymorphism can be a possible prognostic factor in ovarian cancer.

Association of p73 G4C14-A4T14 and p53 codon 72 polymorphism with cervical cancer in Chinese population.

Cervical cancer is known to be the fourth most common cancer among women globally. In various factors, genetic factors have been considered as one major risk factor for cervical cancer. The research of genetic susceptibility to cervical cancer can be greatly helpful in studying the complex mechanism. This study was conducted to identify whether polymorphic variants of p73 G4C14-A4T14 and tumor protein p53 (p53) codon 72, either independently or jointly, might be associated with the risk of cervical cancer. The genotypes of p73 G4C14-A4T14 and p53 codon 72 polymorphisms of peripheral blood DNA from 190 cervical cancer patients and 210 controls were investigated using polymerase chain reaction with confronting two-pair primers and polymerase chain reaction-restriction fragment length polymorphism, respectively. The frequency of p73 G4C14-A4T14 AT/AT (P = 0.013) or p53 codon 72 GG (P = 0.026) genotype was associated with an increased risk of cervical cancer by comparing with the p73 G4C14-A4T14 GC/GC or p53 codon 72 CC genotype, respectively. In addition, the interaction between the p73 G4C14-A4T14 and p53 codon 72 polymorphisms increased the risk of cervical cancer in a multiply manner, with the odds ratio being 3.692 (95% confidence interval =2.106-6.473) for subjects carrying both p73 G4C14-A4T14 GC/AT+AT/AT and p53 codon 72 GG genotypes. These results suggest that there is a statistical difference between p73 and p53 gene polymorphism and the risk of cervical cancer in Chinese women, and there is a potential gene-gene interaction in the incidence of cervical cancer.

The Association of Glutathione S-Transferase P1 Polymorphism to Imatinib Mesylate Resistance in Chronic Myelogenous Leukemia Patients According to Haematology Response at General Hospital Haji Adam Malik and Branch Hospital in Kota Medan

Objective: Variations in the genes coding for drug metabolism enzymes may explain the variability response to treatment. Previous studies reported that GSTP1 polymorphism was associated with the incidence of Imatinib Mesylate resistance as first-line therapy in CML patients. This study aims to determine the association between GSTP1 polymorphism and Imatinib Mesylate resistance in CML patients according to haematology response. Methods: Total of 46 people (consisting of 23 CML patients with Imatinib Mesilat resistance and 23 CML patients without Imatinib Mesilat resistance) at General Hospital H. Adam Malik and branch hospital in Medan City, Indonesia was analyzed in this study. Blood samples were taken for examination of GSTP1 polymorphism through Polymerase Chain Reaction (PCR). Resistance status was taken from medical records based on ELN criteria. Data were analyzed using Fisher's Exact test; p value &lt;0,05 was applied to each statistical test as significant. Result: The distribution of research subjects characteristic was divided into imatinib resistance and non-imatinib resistance groups. In both cases, the highest frequency was found in male (65,2% and 69,6%) in 35-44 years old group (34,8% and 39,1%). In the imatinib resistance group, the highest frequency was found in Javanese (39,1%) and GSTP1 polymorphism Ile/Ile (65,2%). In the non-imatinib-resistant group, the highest frequency was found in Batak tribe (43,5%) and GSTP1 polymorphism Ile/Val (52,2%). This study found 11 cases of leukocytosis and 7 cases of thrombocytosis in the imatinib resistance group. According to statistical measurement, p value was 0,142 (p&gt;0,05). Conclusion: The association of GSTP1 polymorphism to imatinib mesylate resistance in chronic myelogenous leukemia patients according to haematology response was not significant. Keywords: Chronic Myeloid Leukemia, GSTP1 Polymorphism, Imatinib Mesylate Resistance.

SARS-CoV-2: Understanding the Transcriptional Regulation of ACE2 and TMPRSS2 and the Role of Single Nucleotide Polymorphism (SNP) at Codon 72 of p53 in the Innate Immune Response against Virus Infection.

Human ACE2 and the serine protease TMPRSS2 of novel SARS-CoV-2 are primary entry receptors in host cells. Expression of these genes at the transcriptional level has not been much discussed in detail. The ISRE elements of the ACE2 promoter are a binding site for the ISGF3 complex of the JAK/STAT signaling pathway. TMPRSS2, including IFNβ, STAT1, and STAT2, has the PARP1 binding site near to TSS either up or downstream promoter region. It is well documented that PARP1 regulates gene expression at the transcription level. Therefore, to curb virus infection, both promoting type I IFN signaling to boost innate immunity and prevention of virus entry by inhibiting PARP1, ACE2 or TMPRSS2 are safe options. Most importantly, our aim is to attract the attention of the global scientific community towards the codon 72 Single Nucleotide Polymorphism (SNP) of p53 and its underneath role in the innate immune response against SARS-CoV-2. Here, we discuss codon 72 SNP of human p53′s role in the different innate immune response to restrict virus-mediated mortality rate only in specific parts of the world. In addition, we discuss potential targets and emerging therapies using bioengineered bacteriophage, anti-sense, or CRISPR strategies.

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.

Association of VEGF and p53 Polymorphisms and Spiral Artery Remodeling in Recurrent Pregnancy Loss: A Systematic Review and Meta-Analysis.

Many studies have reported the association of VEGF-1154G/A, VEGF 936C/T, and p53 Arg72Pro polymorphisms with recurrent pregnancy loss (RPL), but the outcomes are inconsistent. We have used a meta-analysis to associate these polymorphisms with RPL, having the spiral artery remodeling as a major risk factor. The studies were identified from three different reputed databases, namely ScienceDirect, PubMed/Medline, and Scopus. The eligible studies of VEGF-1154G/A, VEGF 936C/T, and p53Arg72Pro polymorphisms associated with the RPL were selected for the analysis. They were segregated into three different ethnic groups as Asians, Caucasians, and mixed population. For the analysis, the overall prevalence, odds ratio, risk ratio, relative risk ratio, and p-values were calculated. A total of 3,241 RPL cases and 3,205 healthy controls from 21 different case-control studies were analyzed. RPL was highly prevalent in the mixed population with VEGF-1154G/A and p53 Arg72Pro polymorphisms (70.04 and 66.46%, respectively) and in the Asian population with VEGF 936C/T polymorphism (53.58%). The homozygous recessive genotypes of VEGF and p53 exhibited significant association between the respective polymorphisms and RPL along with the increased risk of outcome. The current analysis conclusively reports the geographic distribution of the different genetic polymorphisms which shows high association with the progression of RPL. Understanding the spectrum of polymorphisms on different populations with the spiral artery remodeling as a risk factor encloses the importance of the vasculature during the pregnancy.