Polymorphisms in the 5′-UTR of PTEN and other gene polymorphisms in normal Japanese individuals

Polymorphisms are distributed differently in populations, including those of regions, ethnic groups, and diseased patients. In order to investigate variation in nucleotide sequences in normal individuals, we isolated genomic DNA from the blood of healthy Japanese individuals and sequenced the 5'-untranslated region (5'- UTR) of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene and the gene promoter, intron, and exon nucleotides of p53, p14ARF, murine double minute 2 (MDM2), and the β2- and β3-adrenoceptor (-AR). We found polymorphisms in these regions, including a deletion at positions –465 to –463 and a substitution at position –404 in PTEN and a substitution at position –4924 in p14ARF, in normal individuals. Individuals with or without the PTEN polymorphism harbored a different distribution of polymorphisms, including simultaneous alterations in nucleotides of p53, MDM2, and β3-AR, and also harbored some polymorphic nucleotides located in the same set of associatively altered nucleotides. Our results show that multiple nucleotides, including the PTEN nucleotides, are altered in normal Japanese individuals and provide useful information for genotyping studies in individuals and populations.Полиморфизмы широко распространены в популяциях, включая регионы, этнические группы и больных пациентов. Для исследования изменчивости нуклеотидных последовательностей у нормальных индивидов , мы выделили геномную ДНК из крови здоровых японцев и секвенировали 5′-нетранслируемый участок (5′-UTR) гена фосфатазы и гомолога тензина (PTEN), промоторные последовательности, интроны и экзоны генов p53 и p14ARF, ингибитора супрессора опухолевого роста p53 (MDM2) и генов β2- and β3-адренореце (-AR). Мы обнаружили полиморфизм по этим участкам, включая делецию в положении с −465 to −463 и замену в положении −404 в PTEN и замену в положении −4924 в p14ARF у нормальных индивидов. Индивиды с и без полиморфизма PTEN имели различное распределение полиморфизма, включая одновременные изменения в нуклеотидах p53, MDM2 и 3-AR, и также имели полиморфные нуклеотиды, локализованные в том же наборе совместно измененных нуклеотидов. Наши результаты показывают, что множественные нуклеотиды, включая нуклеотиды PTEN, изменены у нормальных японских индивидов и дают полезную информацию для исследований по генотипированию индивидов и популяций

Polymorphisms in P21 (CODON 31) and P53 (CODON 72) : association with breast cancer susceptibility in the Turkish and Greek populations

Cataloged from PDF version of article.The aim of this study was to investigate the potential association of p53 codon 72 and/or p21 codon 31 polymorphisms with increased susceptibility for breast cancer either independently or combined in the Turkish and Greek populations. A case-control study was conducted for both populations and the genotypes of the subjects were determined by PCR-RFLP (Turkish; p53 genotypes for 274 cases and 221 controls, p21 genotypes for 322 cases and 246 controls, Greek; p53 genotypes for 138 cases and 138 controls, p21 genotypes for 156 cases and 136 controls were obtained). Binary logistic regression was used to analyze the data. Although the Greek study population alone did not give statistically significant results, the p53 codon 72 Arg/Arg inheritance was found to be significantly associated with breast cancer susceptibility in the Turkish study population (OR=2.16; 95% CI=1.08-4.31) as well as in the combined population of Turkish and Greek subjects (OR=2.35; 95% CI=1.25-4.41). This association was further increased with increased BMI (OR=3.86; 95% CI=1.12-13.26) in the Turkish population but the result should be treated with caution because of the wide confidence interval. The inheritance of the combined p21 codon 31 Arg/Arg or Ser/Arg genotypes increased breast cancer susceptibility in the Turkish study population (OR=1.15; 95% CI=0.75-1.76) although the result is not statistically significant. The most prominent result of this study is that there is an interaction between the p53 Arg72Arg and p21 Arg31Arg or Ser31Arg genotypes for breast cancer susceptibility (OR=2.66; 95% CI=1.06- 6.66). These results let us to conclude that there is a strong association between the p53 Arg72Arg genotype and breast cancer risk in the Turkish population and that the combination of high-risk allelic variants of both p53 and its downstream effector protein p21 may have a role as a risk factor for breast cancer development.Çolakoğlu, GülsenM.S

Analysis of GSTM1, GSTT1, GSTP1, and TP53 polymorphisms as genetic risk factors for bladder cancer in the Turkish population

Ankara : The Department of Molecular Biology and Genetics and the Institute of Engineering and Science of Bilkent University, 2001.Thesis (Ph.D.) -- Bilkent University, 2001.Includes bibliographical references.The effect of the GSTM1 and GSTT1 null genotypes, the GSTP1 Ile105Val, and TP53 Arg72Pro polymorphism on bladder cancer susceptibility was investigated in a case control study of 121 bladder cancer patients, and 121 age-sex matched controls in the Turkish population. The adjusted odds ratio (for age, sex, and smoking status) for the GSTM1 null genotype is 1.94 (95% CI 1.15- 3.26) and for the GSTP1 105 Ile/Val or Val/Val genotypes is 1.75 (95% CI 1.03- 2.99). GSTT1, and TP53 loci was not shown to be associated with bladder cancer. Combination of the two high risk genotypes, GSTM1 null and GSTP1 105 Ile/Val or Val/Val, revealed that the risk increases by 3.91 times (95% CI 1.88-8.13) when compared with the combination of the low risk genotypes of these loci. In individuals with a combined risk of cigarette smoking and the GSTM1 null genotype, bladder cancer risk is 2.81 (95% CI 1.23-6.35) relative to persons who do not smoke and carry the GSTM1 present genotype. The same risk for the GSTP1 105 Ile/Val or Val/Val genotypes is 2.38 (95% CI 1.12-4.95). These findings support the role for the GSTM1 null and the GSTP1 105 Ile/Val or Val/Val genotypes in the development of bladder cancer. Furthermore, gene-gene (GSTM1- GSTP1) and gene-environment (GSTM1-smoking, GSTP1-smoking) interactions increase this risk substantially.Törüner, Gökçe AltayPh.D

Gene polymorphisms and risk of head and neck squamous cell carcinoma: a systematic review

Background: Exposure to the same environmental factors in different people have resulted in different susceptibility to head and neck squamous cell carcinoma (HNSCC), which suggests genetic variation may be a risk factor for the development of HNSCC. So, the aim was to review literatures on the association between gene polymorphisms and risk of HNSCCs. Materials and methods: This systematic review included all articles on the impact of gene polymorphisms on risk and susceptibility to HNSCC published till September 2021 using PubMed, Web of science, SCOPUS, Google Scholar and Cochrane library databases. Results: Of 1163 initial searched articles, 77 articles were eligible to include in this review. Studies were categorized based on gene functions. In each category, studied gene polymorphisms related to growth control genes, cell cycle control, apoptosis, DNA repair genes, carcinogen-metabolizing enzymes, alcohol-metabolizing genes, antioxidant gene, inflammatory cytokine, transcription factor, tumor immunity, folate metabolism, and tumor suppressor gene were discussed separately. Among the polymorphisms that are often significantly associated with HNSCC risk are: GSTM1 null, GSTT1 null, CYP2D6 *4, XRCC1 Arg194Trp and Arg399Gln, ERCC1 C8092A, XPD  Lys751Gln, XRCC3 Thr241Met, P53 codon 72 and MTHFR C677T polymorphisms. Conclusion: Varied and contradictory results have been reported in different studies regarding the association of gene polymorphisms with HNSCC risk. To conclude about this association and to overcome these contradictions, it is necessary to use the results of existing meta-analyses or to perform new or updated meta-analyses.

Double-Edged Sword of Tumour Suppressor Genes in Schizophrenia

Schizophrenia (SCZ) is a common psychiatric disorder with polygenetic pathogenesis. Among the many identified candidate genes and loci, the group of tumour suppressor genes has drawn our interest. In this mini-review article, we describe evidence of a correlation between major tumour suppressor genes and SCZ development. Genetic mutations ranging from single nucleotide polymorphisms to large structural alterations have been found in tumour-related genes in patients with SCZ. Epigenetic mechanisms, including DNA methylation/acetylation and microRNA regulation of tumour suppressor genes, have also been implicated in SCZ. Beyond genetic correlations, we hope to establish causal relationships between tumour suppressor gene function and SCZ risk. Accumulating evidence shows that tumour suppressor genes may mediate cell survival and neural development, both of which contribute to SCZ aetiology. Moreover, converging intracellular signalling pathways indicate a role of tumour suppressor genes in SCZ pathogenesis. Tumour suppressor gene function may mediate a direct link between neural development and function and psychiatric disorders, including SCZ. A deeper understanding of how neural cell development is affected by tumour suppressors may lead to improved anti-psychotic drugs

Novel TMC8 splice site mutation in epidermodysplasia verruciformis and review of HPV infections in patients with the disease

Epidermodysplasia verruciformis (EV) is a genodermatosis leading to infections with cutaneous HPV, persistent plane warts and a high rate of non-melanoma skin cancer (NMSC). Biallelic loss-of-function mutations in TMC6 and TMC8 are known to be causative.; The aim of this study was to report EV-causing mutations in four patients with EV and to give an overview of all described patients with EV.; We investigated four patients with classical features of EV from two families. All patients were affected by plane warts with typical EV histology since early childhood, and β-HPVs were detected on their skin. One patient had recurring cutaneous squamous cell carcinomas (cSCC) and carcinomas in situ (Bowen type). We sequenced both TMC6/8 for disease-causing mutations and quantified levels of gene expression. We also performed a systematic literature review to discuss these patients in the context of previously reported cases, mutations already identified, as well as HPV types.; Three patients of one family carried a homozygous splice site mutation in TMC8 resulting in aberrantly spliced transcripts that were not degraded. By contrast, no TMC6/8 mutation was detected in the patient from the other family. A systematic literature review revealed 501 described patients with EV. Around 40% of patients with EV analysed for genetic alterations carried no mutation in TMC6/8. While β-HPVs were identified in the majority of cases, α-HPVs were detected in several individuals.; The relatively high proportion of EV patients without mutation in TMC6/8 indicates the existence of EV-causing mutations in additional, presently unknown gene(s). However, a homozygous TMC8 splice site mutation in our patients resulted in aberrant transcripts which cannot retain the healthy phenotype. The literature review revealed that HPV-5 is the most commonly identified HPV in patients with EV, but HPV-3, HPV-14 and HPV-20 were unexpectedly identified more frequently than HPV-8