P53 Polymorphism Research Articles

Smoking and P53 polymorphism association with chromosomal aberration in lung cancer

Tobacco exposure is the primary leading cause for cancer of the oral cavity, the airways and lung. The carcinogens in cigarette smoke have been linked as an environmental risk factor for causing genetic mutations in tumor suppressor, including TP53 (p53) which has been linked as a causative for occurrence and progression in lung cancer. The aim of the current case-control study is to assess the presence and frequency of chromosomal aberrations between smokers and non-smokers in case and control group. Further, analysis was also extended to include the p53 codon 72 Arg/Pro mutation analysis between the groups of study cohort. In methods, the case-control epidemiological study included a total of 100 cases and controls who were further categorized as smokers and non-smokers for analysis. Chromosomal aberration assay was done on peripheral blood lymphocytes and studied using Geimsa stain, while analysis of the p53 codon 72 Arg/Pro mutation was done by allele-specific polymerase chain reaction assay. The chromosomal aberration assessed include structural abnormalities like breaks, fragment, dysenteric and gaps, as well as numerical aneuploidies. Results showing the number of chromosomal aberrations was higher among smoker cases as compared to controls, and numerical aneuploidy was also detected only among this cohort. The mean of chromosomal aberrations observed between cases and controls and smokers as well as non-smokers was significant at p < 0.0001. In case of the p53 genotyping result, the frequency of the Arg/Arg allele was higher among controls as compared to cases and the difference significant at p < 0.005. Among female participants, the difference between Arg/Arg and Pro/Arg was also found to be significant between cases and controls. Combined analysis of the p53 codon 72 alleles and mean of chromosomal aberrations between cases and controls was found to be significant at p < 0.005. Our study found an association between risk of lung cancer as well as occurrence of chromosomal aberrations. In case of the p53 polymorphism, the significance was detected only among females. In Conclusion, the studied p53 variant and chromosomal aberration along with smoking has shown significant association with increased risk of lung cancer.

Crosstalk of Cyclin-dependent kinase inhibitor 1A (CDKN1A) gene polymorphism with p53 and CCND1 polymorphism in breast cancer.

Mutations and polymorphisms in genes of cell- cycle and apoptosis regulatory pathway influence the breast cancer risk. Analysis of single low penetrance mutant alleles may not reflect the precise risk association when analyzed alone. A total of 115 DNA samples extracted from breast cancer patients and an equal number of age and sex-matched normal controls were used for polymorphic analysis. Genotyping for p21 rs1801270 and CCND1 rs603965 was done by PCR-RFLP method while AFLP method was used for p53 rs1042522 single nucleotide polymorphism detection. Statistical methods included simple mean±SD and correlation coefficient to analyze the risk of association of p21, p53 and CCND1 SNPs and breast cancer. Individuals harboring SNPs in p21, p53 and CCND1 genes namely rs1801270, rs1042522 and rs603965, respectively were rendered increasingly susceptible to developing breast cancer when compared with normal controls. Our report emphasizes the need of combinational analysis of low-penetrance mutant alleles to assess accurately their association with breast cancer risk. Future case-control studies analyzing gene-environment interactions across different populations may confirm reported risk associations of studied polymorphisms with developing breast cancer.

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.

Use of different approaches for the culture-independent typing of Mycoplasma pneumoniae from two geographically distinct regions

We used multi-locus variable-number of tandem repeat analysis (MLVA), p1, multi-locus sequence (MLS) and single nucleotide polymorphisms (SNP) typing to characterize a collection of Mycoplasma pneumoniae strains from Cuba and Germany. Among 67 strains, 5 p1, 7 MLVA, 11 MLS, and 11 SNP types were obtained.

Association of p53 (P72R) gene polymorphism with increased risk of diabetes mellitus in center of Iran (Tehran)

BackgroundDiabetes mellitus (DM) is increasingly recognized as a serious worldwide public health concern. P53 has a significant effect on glucose metabolism pathways and insulin secretion. The major objective of this study was to investigate association between rs1042522 polymorphism in p53 and the risk of developing DM in Iranian population. MethodsDiabetic patients (T1DM = 142 patients, T2DM = 200) admitted to the endocrine center of Artesh Hospital in Tehran and 322 healthy individuals were genotyped for the rs1042522 polymorphism (TP53 gene) by the polymerase chain reaction-restriction fragment length polymorphism technique. The χ2 test and Student's t-test were applied to compare genotype and allele distributions and clinical characteristics between the two groups. ResultsA significant difference was found between the genotype frequencies of p53 -1042522C/G SNP in T1DM patients with their controls (χ2 = 8.62, df = 2, P = 0.013) and T2DM patients with their controls (χ2 = 19.9, df = 2, P < 0.001). Significant associations of the G allele [T1DM: OR = 0.860 (0.531–1.395, P = 0.542), T2DM: OR = 0.384 (0.253–0.581, P < 0.001)] and CG + GG genotype [T1DM: OR = 1.973 (0.982–3.963, P = 0.056), T2DM: OR = 3.88 (2.096–7.185, P < 0.001)] with DM were identified. ConclusionThis paper has argued that individuals with G allele of SNPrs1042522 (TP53 gene) have an increased risk of developing T2DM.

Role of glutathione S-transferase P1 polymorphism in early transplant complications in patients undergoing allogeneic stem cell transplantation.

Complications in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) cause serious morbidity and mortality. Predicting patients at risk in advance and changing the symptomatic care and/or preparation regimen according to this risk assessment have been emphasized recently. Several single-nucleotide polymorphisms have been studied, and some were found to be responsible for early complications. Glutathione S-transferase P1 (GSTP1) is an enzyme involved in the detoxification process that reduces oxidative stress by reducing the number of free oxygen radicals. This study aimed to investigate the relationship between GSTP1 polymorphism and early complications of allo-HSCT, iron parameters, overall survival (OS), and transplantation-related mortality (TRM). A total of 50 patients diagnosed with acute myeloid leukemia (n = 23) or acute lymphoblastic leukemia (n = 27) who underwent allo-HSCT between May 2008 and February 2011 at Gazi University Faculty of Medicine, Stem Cell Transplantation Unit, were included. Of the 50 patients, 24 (48%) were women and 26 (52%) were men. The median age of the patients was 26 (16-74) years. GSTP1 polymorphism was detected in 23 (46%) patients, and 27 (54%) had no polymorphism (wild type). The two groups were compared in terms of early toxicity after transplantation, according to the preparation regimen. The group with GSTP1 polymorphism was found to have a high transferrin saturation index (P < 0.05). Patients with no GSTP1 polymorphism showed a high grade III-IV anemia ratio (P < 0.05). The presence of sinusoidal obstruction syndrome and graft-versus-host disease was similar in both groups (P > 0.05). OS and TRM were higher in the GSTP1 polymorphism group, but no statistical difference was found between the two groups (P > 0.05). TSI was higher in the GSTP1 polymorphism group. GSTP1 polymorphism had no effect on early transplantation complications. Although the OS and TRM ratios were higher in the GSTP1 polymorphism group, no statistically significant difference was found between the groups. Further studies with larger sample size are needed.

Title: Association of p53 and p21 gene polymorphism and risk of gastrointestinal cancer in rural population of south western Maharashtra: A hospital based case-control study.

Title: Association of p53 and p21 gene polymorphism and risk of gastrointestinal cancer in rural population of south western Maharashtra: A hospital based case-control study.

Association between p53 and p21 genes polymorphisms and ulcerative colitis in an Iranian population

Ulcerative colitis is an inflammatory disease characterized by ongoing mucosal and submucosal changes, starting from the rectum and spreading to proximal regions. The p53 gene is considered as the most important tumor suppressor gene, encoding for a 53 k Dalton phosphoprotein, whose natural function is to protect the genome against damages by activation of the P21 protein. The P21 protein, in turn, causes cell cycle arrestment at the G1/S phase through inhibition of the CDK1 and CDK2 activity, and thus, permits DNA repair.In this study, we investigated the association of the p53 codon 72 and p21 codon 31 polymorphisms with ulcerative colitis in the north of Iran using RFLP-PCR assay. A total number of 174 patients with intestinal ulcers and 82 healthy controls were genotyped for p53 codon 72 and p21 codon 31 polymorphisms.The Arg/Arg genotype of p53 gene codon 72 was associated with an increased risk for ulcerative colitis (OR, 4.074; 95% CI,5.874–1.800), compared with the Pro/Pro genotype. Also, the Ser/Ser genotype of p21 gene codon 31 was associated with an increased risk of ulcerative colitis (OR, 3.175; 95% CI, 4.875–1.700), compared with the Arg/Arg genotype. Also, we found a significant relationship between ulcerative colitis with age, metastasis, and cancer stage, but no relationship with gender was found )Chi-Square p < 0.05).The findings suggest that genetic polymorphisms of the p53 gene codon 72 and p21 gene codon 31 were significantly associated with ulcerative colitis and could be used as a prognostic marker for ulcerative colitis and gastrointestinal malignancies.

Measurement of the Gene Expression and Polymorphisms of c-myc and p53 Genes in HBV Infected Patients

This study explained the c-myc and p53 gene expression and polymorphisms in chronic (40), cirrhosis (30) and Hepatocellular Carcinoma, (HCC) (30) patients related to Hepatitis B Virus (HBV) infection and healthy control (50) in Egypt. Where, c-myc (intron 8) and p53 (codon 72) gene expression and polymorphisms were determined using qRT-PCR and PCR-RFLP techniques. The results showed that c-myc gene expression (2-ddct) was significantly increased in chronic (1.38), cirrhosis (1.47) and HCC (5.59) compared to the control group (1.00), while p53 gene expression (2-ddct) was significantly decreased compared to the control group (0.82, 0.65, 0.33 and 1.00, respectively). In HCC group, c-myc genotype (CC) was predominant (90%) more than cirrhosis, chronic and control (73.33, 22.5 and 6%, respectively), GG genotype was predominant in control (70%) more than chronic, cirrhosis and HCC groups (67.5, 6.66 and 6.66%, respectively) and GC genotype was high in control (24%) more than cirrhosis, chronic and HCC groups (20, 10 and 3.33%, respectively). p53 PP (88%) genotype was predominant in control more than chronic, cirrhosis and HCC groups (30, 30 and 6.66%, respectively), AA genotype was predominant in HCC group (73.33%) more than chronic, cirrhosis and control (50, 10 and 4%, respectively) and genotype PA was predominant in cirrhosis (60%) more than chronic, HCC and control (20, 20 and 8%, respectively). These results suggest clearly that both c-myc and p53 gene expression and polymorphisms influence clinical outcome and progression of HBV infection and then considered an accurate genetic biomarker to determine and predict the progression of HBV infection.

Evaluation of 40-bp deletion/insertion polymorphism of mdm2 and 16-bp deletion/insertion polymorphism of p53 gene in patients with lymphoma in a Persian population

Considering the importance of lymphoma and its prevalence in communities as well as its relationship with genetic factors (P53 &amp; MDM2) as well as contradictory results about the possible role of deletion/insertion of polymorphisms in different types of cancer. The aim of this study was to investigate the deletion/insertion of 40 bp of mdm2 polymorphism and 16-bp of p53 polymorphism in patients with lymphoma. In this case-control study, 152 non-Hodgkin's lymphoma patients and 155 healthy individuals were selected by convenience sampling method. MDM2 and P53 polymorphisms were examined by PCR. SPSS V22 software was used to interpret the results. The results of the study showed that rs3730485 species was associated with the risk of lymphoma. The Ins / Del and Del / Del genotypes reduce the risk of lymphoma compared to the Ins / Ins genotype (OR = 0.41,95% CI = 0.25-0.65 P &lt;0.001 and OR = 0.33.95% CI = 0.12). 0.96, P = 0.035 In relation to Ins / Del + Del / Del and Ins / Del, the results also showed that they reduce the risk of lymphoma (OR = 0.40,95% CI = 0.25-0.63, P &lt;0.001). Results indicated that Ins / Del, Del / Del, Ins / Del + Del / Del and D alleles genotypes had a statistically significant relationship with lymphoma risk. Due to the fact that the OR genotypes of this site are less than one step away, it is a protective factor for lymphoma, so that these alleles and the mentioned genotype reduce the risk of lymphoma.

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.

The morbidity and mortality of COVID-19 are correlated with the Ile105Val glutathione S-transferase P1 polymorphism

BackgroundOxidative stress is an important issue in coronavirus disease 2019 (COVID-19). Considering that glutathione S-transferase P1 (GSTP1) is involved in cellular detoxification, it may play an important role in susceptibility to infection with SARS-CoV-2 and/or its outcome. In the present study, the association between the Ile105Val GSTP1 polymorphism (rs1695) and susceptibility to SARS-CoV-2 infection, as well as its outcome was investigated. Data on the prevalence (per 106 people), case-fatality (per 100 infected cases), and mortality (per 106 people) of COVID-19 and various potential confounders (the life expectancy at birth, density of medical doctors, density of nursing and midwifery personnel, and the gross national income per capita) were used. The latest data available for 45 countries were used for the study.ResultsIn multivariate linear regression analyses, the Val105 allelic frequency showed positive association with the log-prevalence (partial r = 0.308, p = 0.042) and log-mortality of COVID-19 (partial r = 0.316, p = 0.037). The log-fatality did not show association with the allelic frequency. In the next step, only countries with the gross national income per capita more than $15,000 were included in the analysis. In the selected countries, the frequency of Val105 was positively associated with the log-prevalence (partial r = 0.456, p = 0.009) and log-mortality of COVID-19 (partial r = 0.544, p = 0.001).ConclusionsThe present findings indicate that countries with higher Val105 allelic frequency of the rs1695 polymorphism showed higher prevalence and mortality of COVID-19.

Exploring the p53 connection of cervical cancer pathogenesis involving north-east Indian patients.

As per WHO, Cervical cancer (CaCx) is a global issue, being the fourth common cancer in women with incidence rate of 13.1 per 1 lakh women globally and accounting for 311000 deaths in the year 2018 itself globally. The molecular pathogenesis in Human papillomavirus (HPV) infected cases is inconclusive. The detection of molecular factors leading to progression of CaCx can be important in the diagnosis and management of the disease. p53 a known tumor suppressor gene having a regulative role in cell cycle has been highlighted as key factor in the prevention of cancer but its significance in CaCx cases has been variably documented. The present study therefore targeted to evaluate the significance of p53 profile in CaCx cases in ethnically distinct northeast Indian population. Blood and Tissue samples (N = 85) of cervical cancer patients were collected and screening for HPV was performed using PCR. Thereafter the differential mRNA expression(qPCR), Immunohistochemistry, Mutation (PCR direct sequencing method) of p53 was studied. Further p53 epigenetic profiling was done by Methylation specific PCR (MS-PCR) and western blotting by using p53 acetylation specific antibodies. Our findings revealed that the downregulation of p53 was associated with the progression of disease and the variation in downregulation based on p53 polymorphism was observed. Further hypermethylation and deacetylation of p53 was also found to be associated with the pathogenesis of CaCx. The downregulated expression and hypermethylation of p53 in lower grade of CaCx, together established its association with the progression of CaCx from lower to severe grade. Therefore, in CaCx patients of northeast Indian population, malfunctioning of p53 is found to have significant role in cervical cancer progression.

Correlation between P53 Arg72Pro and MDM4 gene rs4245739 polymorphisms in breast cancer

BackgroundMDM4 is a negative regulator of p53 tumor suppression pathway. Various studies reveal the fact that the rs4245739A>C polymorphism of MDM4 in 3′-untranslated region is targeted by miR-191 which leads to lower MDM4 expression. On the other hand, the importance of Arg72Pro polymorphism of p53 in breast cancer is proven. The aim of this study is to present the correlation between the aforementioned SNPs and the risk of breast cancer. The statistical society of the study includes 199 healthy women as the control group and 206 women suffering from breast cancer included from Turkish population of the East Azarbaijan. ResultsAlleles of both positions are detected through Tetra-ARMS PCR while SPSS and the SHEsis, online software was exerted for allele typing, genotyping, and haplotype analysis. Different alleles of both MDM4 rs4245739 and p53 Arg72Pro had no significant frequency in patients (P > 0.05). Furthermore, genotypes of neither MDM4 rs4245739 nor p53 Arg72Pro could increase or decrease the risk of breast cancer in patients compared to healthy women. Additionally, a significant factor affecting the risk of breast cancer is gene-gene interaction. The results of the ongoing study revealed that two genetic variants, MDM4 rs4245739 and p53 Arg72Pro polymorphisms, failed to be associated, individually and combined together, with the risk of breast cancer. However, additional well-designed studies on large populations are required to validate such an association. ConclusionVarious alleles of both SNPs had no significant frequency difference between patients and controls. Moreover, genotypes of neither MDM4 nor p53 were significantly distributed in women with breast cancer compared to the healthy controls. Meanwhile, haplotype analysis failed to be significant. Last but not least, all clinical manifestations, other than association between tumor size and MDM4 genotypes could not be correlated with either various alleles or genotypes.

A Case-Control Study on the p73 G4A Gene Polymorphism and Susceptibility to Breast Cancer in an Iranian Population

The tumor protein p73 (TP73) is a homolog of TP53 family. Ectopic p73 overexpression largely mimics p53 activities as a tumor suppressor and activates the transcription of p53-responsive genes and as a result induce apoptosis. This study aimed to investigate the association between p73 G4A polymorphism and the risk of breast cancer in a northeastern Iranian population. This case-control study was performed on 105 patients who admitted in educational hospitals of Mashhad University of Medical Sciences, Iran during 2013-2015, with breast cancer as case group and 120 healthy women as the control group. PCR-CTPP method was used to investigate the relationship between the p73 G4A polymorphism and the risk of breast cancer. There was no significant association between the AA genotype of the p73 G4A polymorphism and breast cancer in case and control groups. Although G allele frequency was higher in the case group, the abundance of this allele between case and control groups was not statistically meaningful and, as a result, not associated with the risk of breast cancer in this study group. There was no association between G4A p73 polymorphism and the risk of breast cancer in a northeastern Iranian population.

Estimating the Effect of Single-Point Mutations on Protein Thermodynamic Stability and Analyzing the Mutation Landscape of the p53 Protein.

Nonsynonymous single-nucleotide polymorphisms often result in altered protein stability while playing crucial roles both in the evolution process and in the development of human diseases. Prediction of change in the thermodynamic stability due to such missense mutations will help in protein engineering endeavors and will contribute to a better understanding of different disease conditions. Here, we develop a machine-learning-based framework, viz., ProTSPoM, to estimate the change in protein thermodynamic stability arising out of single-point mutations (SPMs). ProTSPoM outperforms existing methods on the S2648 and S1925 databases and reports a Pearson correlation coefficient of 0.82 (0.88) and a root-mean-squared-error of 0.92 (1.06) kcal/mol between the predicted and experimental ΔΔG values on the long-established S350 (tumor suppressor p53 protein) data set. Further, we estimate the change in thermodynamic stability for all possible SPMs in the DNA binding domain of the p53 protein. We identify single-nucleotide polymorphisms in p53 which are plausibly detrimental to its structural integrity and interaction affinity with the DNA molecule. ProTSPoM with its reliable estimates and time-efficient prediction is well suited to be integrated with existing protein engineering techniques. The ProTSPoM web server is accessible at http://cosmos.iitkgp.ac.in/ProTSPoM/.

Glutathione S-Transferase P1 Polymorphism on Exon 6 and Risk of Hepatocellular Carcinoma in Thai Male Patients

Introduction: Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the fourth leading cause of cancer-related deaths worldwide. HCC cases are two to four times more common in males than in females, and the highest incidence is found in Asia and Sub-Saharan Africa. This gender disparity is the result of different behavioral risk factors, such as smoking and drinking alcohol. Glutathione S-Transferase P1 (GSTP1) is an enzyme that is involved in the detoxification of carcinogenic electrophiles. GSTP1 codon 105 in exon 5 and codon 114 in exon 6 polymorphisms result in decreased enzyme detoxification activity, which is the cause of many cancers. Objectives: This study aims to investigate the associations between GSTP1 polymorphism, HCC patients, and the risk factors for HCC. It is hoped that this research will provide useful knowledge on the effects of genetic GSTP1 polymorphism in Thai HCC patients. Methods: DNA from 44 Thai HCC patients and 52 healthy controls was analyzed for GSTP1 exon 5 and exon 6 polymorphisms by PCR-RFLP. The associations between GSTP1 polymorphism, the control group, and clinicopathological parameters were determined. Results:The results show that GSTP1 exon 6 polymorphism genotypes (C/T) were correlated with an increased risk of HCC susceptibility (OR = 4.40). Moreover, exon 6 polymorphism genotypes (C/T) were associated with the gender of patients (p = 0.015), but no relationships were found between GSTP1 exon 5 polymorphism and the clinicopathological data of patients. Conclusions: The results suggest that the GSTP1 exon 6 polymorphism genotype was associated with an increase in the risk of HCC in male patients and that it tended to be related to cancer differentiation. No association was found between GSTP1 exon 5 polymorphism and the risk of HCC.

Association of Lipid Peroxidation/Antioxidant System Activity with Glutathione S-Transferase P1 Polymorphisms in Infertile Men

Association of Lipid Peroxidation/Antioxidant System Activity with Glutathione S-Transferase P1 Polymorphisms in Infertile Men

Analysis of polymorphisms, promoter methylation, and mRNA expression profile of maternal and placental P53 and P21 genes in preeclamptic and normotensive pregnant women

BackgroundPreeclampsia (PE), as a multisystem disorder, is associated with maternal hypertension and proteinuria. Apoptosis seems to be involved in the pathophysiology of PE, although its precise pathogenic mechanisms are not well established. In this study, we aimed to identify the association between maternal TP53-rs1042522, P21-rs1801270, and P21-rs1059234 polymorphisms and PE. In addition, we examined the effects of promoter methylation and TP53 and P21 polymorphisms on placental mRNA expression in PE women.MethodsThe blood of 226 PE women and 228 normotensive pregnant women was examined in this study. In addition, the placentas were genotyped in 109 PE and 112 control women. The methylation status was assessed by a methylation-specific PCR assay, while mRNA expression was examined via Quantitative Real Time PCR.ResultsThe maternal and placental P21-rs1801270 CA genotype had a significant association with the reduced risk of PE. In the dominant, recessive, and allelic models, maternal/placental P21-rs1059234 polymorphism had no statistically significant association with the risk of PE. On the other hand, the reduced risk of PE was associated with maternal, but not placental TP53-rs1042522 polymorphism in the dominant and recessive models. The maternal and placental P21-rs1801270 polymorphism was associated with PE risk. The maternal P21 Trs1059234Crs1801270 haplotype was associated with 3.4-fold increase in PE risk, However the maternal P21 Trs1059234Ars 1801270 haplotype and placental Crs1059234CA rs1801270 haplotype led to 0.5 and 0.4-fold decrease in PE risk, respectively. PE women showed 5.6 times higher levels of placental mRNA expression of TP53 gene, although it was not associated with rs1042522 polymorphism. The relative placental mRNA expression of P21 gene was 0.2 in PE women. It was also 2.4 times higher in individuals with rs1801270CA genotype than those with AA genotype. The hyper-methylation of P21 and TP53 genes in the promoter region was associated with a 3.4-fold and 3-fold increase in PE risk, respectively. However, no association was found between P21 and TP53 mRNA expression and promoter methylation.ConclusionIn conclusion, P21-rs1801270 and TP53-rs1042522 polymorphisms were involved in reduced risk of PE. P21-rs1801270 was associated with decreased P21 mRNA expression. The hyper-methylation of P21 and TP53 genes in the promoter region was associated with a higher PE risk.

Association between host TNF-α, TGF-β1, p53 polymorphisms, HBV X gene mutation, HBV viral load and the progression of HBV-associated chronic liver disease in Indonesian patients.

In developing countries, including Indonesia, there is a high mortality rate associated with the progression of hepatitis B virus (HBV)-associated chronic liver disease (CLD). The pathogenesis of HBV infection is influenced by viral and host factors. To determine potential associations between these factors, host single nucleotide polymorphisms (SNPs) on TNF-α, TGF-β1 and p53, HBV X gene mutation and HBV viral load were investigated in patients with HBV-associated CLD in Surabaya, Indonesia. Sera were collected from 87 CLD patients with HBV infection. TNF-α, TGF-β1 and p53 SNPs were genotyped by PCR restriction fragment length polymorphism. The HBV X gene was sequenced and compared with reference strains to determine mutations and the viral load was measured using reverse transcription-quantitative PCR. In Indonesian patients, no association between TNF-α, TGF-β1 and p53 SNPs and CLD or X gene mutation were identified. A total of 23% (20/87) of samples had HBV X gene mutations, including ten substitution types, one deletion and one insertion. Multinomial regression analysis revealed that the K130M/V131I mutations were correlated with CLD progression (OR, 7.629; 95% CI, 1.578-36.884). Significant differences in viral load were found in HBV-infected patients who had X gene mutations, such as R87W/G, I127L/T/N/S and K130M/V131I mutations (P<0.05). The presence of K130M and V131I mutations may be predictive for the progression of HBV-associated CLD in Indonesia.