Polymorphisms In Different Genes Research Articles

Unveiling the microevolution of antimicrobial resistance in selected Pseudomonas aeruginosa isolates from Egyptian healthcare settings: A genomic approach

The incidence of Pseudomonas aeruginosa infections in healthcare environments, particularly in low-and middle-income countries, is on the rise. The purpose of this study was to provide comprehensive genomic insights into thirteen P. aeruginosa isolates obtained from Egyptian healthcare settings. Phenotypic analysis of the antimicrobial resistance profile and biofilm formation were performed using minimum inhibitory concentration and microtiter plate assay, respectively. Whole genome sequencing was employed to identify sequence typing, resistome, virulome, and mobile genetic elements. Our findings indicate that 92.3% of the isolates were classified as extensively drug-resistant, with 53.85% of these demonstrating strong biofilm production capabilities. The predominant clone observed in the study was ST773, followed by ST235, both of which were associated with the O11 serotype. Core genome multi-locus sequence typing comparison of these clones with global isolates suggested their potential global expansion and adaptation. A significant portion of the isolates harbored Col plasmids and various MGEs, all of which were linked to antimicrobial resistance genes. Single nucleotide polymorphisms in different genes were associated with the development of antimicrobial resistance in these isolates. In conclusion, this pilot study underscores the prevalence of extensively drug-resistant P. aeruginosa isolates and emphasizes the role of horizontal gene transfer facilitated by a diverse array of mobile genetic elements within various clones. Furthermore, specific insertion sequences and mutations were found to be associated with antibiotic resistance.

Los Polimorfismos en la Uteroglobina y en IL2R están asociados con el daño articular y/o la Cirugía articular en pacientes con Artritis Reumatoide

Introduction and Objectives. Of all clinical manifestations that mark prognosis of a patient with RA, radiological damaged is considered one of the most important variables. In addition to clinical and laboratory markers are increasingly studying the influence of genetic factors in the predictive ability of the RA forecast. Previous studies have reported misleading results about polymorphisms in different genes associated with radiological damage in RA. The aim of this study was to assess the involvement of the clinical, analytical and genetic variables in the radiological damage in a Spanish RA population. Methods. Six hundred thirty-two Spanish RA patients were included. SNP genotyping was performed using an oligonucleotide microarray. Allele and genotype association analyses with articular damage and a haplotype association test were performed. Results. This study includes retrospectively 604 Spanish RA patients with articular erosions and 616 with surgery due to RA. The A587G polymorphism (rs3741240) in uteroglobin gene was associated with increased radiological damage defined by phenotypes RX2 (multiple erosions on hands and feet) and surgery due to RA (OR 1.6 and 1.7 respectively). IL2R polymorphism was associated with RX2 phenotype (OR 2.95). Disease duration, painful joints, ESR, RF and ACPA are the analytical and clinical variables significantly associated with articular damage. Conclusions. These results demonstrate that the A587G and C4599T polymorphism in uteroglobin and IL2R genes respectively are associated with radiological damage in a Spanish RA population.

Molecular Tools for Typing Mycoplasma pneumoniae and Mycoplasma genitalium

Mycoplasma pneumoniae and Mycoplasma genitalium are cell wall-less bacteria with strongly reduced genome content and close phylogenetic relatedness. In humans, the only known natural host, the microorganisms colonize the respiratory or genitourinary mucosa and may cause a broad range of clinical presentations. Besides fundamental differences in their tissue specificity, transmission route, and ability to cause prevalence peaks, both species share similarities such as the occurrence of asymptomatic carriers, preferred populations for infection, and problems with high rates of antimicrobial resistance. To further understand the epidemiology of these practically challenging bacteria, typing of strains is necessary. Since the cultivation of both pathogens is difficult and not performed outside of specialized laboratories, molecular typing methods with adequate discriminatory power, stability, and reproducibility have been developed. These include the characterization of genes containing repetitive sequences, of variable genome regions without the presence of repetitive sequences, determination of single and multi-locus variable-number tandem repeats, and detection of single nucleotide polymorphisms in different genes, respectively. The current repertoire of procedures allows reliable differentiation of strains circulating in different populations and in different time periods as well as comparison of strains occurring subsequently in individual patients. In this review, the methods for typing M. pneumoniae and M. genitalium, including the results of their application in different studies, are summarized and current knowledge regarding the association of typing data with the clinical characteristics of infections is presented.

Discrimination of Patients with Prostate Cancer from Healthy Persons Using a Set of Single Nucleotide Polymorphisms.

Prostate cancer is the second cancer diagnosed in males. It accounts for about 4% of cancer-related mortality in men. Several genetic polymorphisms in different genes have been identified that alter the risk of this kind of malignancy. We used the random forest (RF) algorithm for prediction of prostate cancer risk in Iranian population using 13 different single nucleotide polymorphisms (SNPs) in four genes (ANRIL, HOTAIR, IL-6 and IL-8). The samples were divided into a training set (n=320) and a test set (n=80) to evaluate the generalization power for training algorithm. For hyper-parameters tuning, we used randomized search with 5-fold cross-validation for the following hyper-parameters: (1) Number of trees or estimators in the forest (set from 3 to 500); (2) The maximum number of leaf nodes (set from 2 to 32); (3) The maximum number of features used for the best split (set from 5 to 13); and (4) Using bootstrap samples in the trees building (True or False). Accuracy, sensitivity, specificity, and F1-score in both training and test sets were reported. The most important SNP was ANRIL-rs1333048: A/A (Gini index= 0.096) followed by ANRIL- rs10757278: G/G (Gini index= 0.059). Training Dataset Outcomes were as follow: Accuracy: 0.896, Sensitivity: 0.85, Specificity: 0.944 and F1 Score: 0.891. Test Dataset Outcomes were as follow: Accuracy: 0.787, Sensitivity: 0.775, Specificity: 0.800 and F1 Score: 0.784. The AUC Scores were 0.966 and 0.841 for training and test datasets, respectively. The proposed panels of SNPs can predict risk of prostate cancer in Iranian population with appropriate accuracy.

Pharmacogenetics Update on Biologic Therapy in Psoriasis.

Background and objectives: Psoriasis is a chronic immune-mediated skin disease caused by several complex factors, both environmental and genetic, many of which are still not fully understood. Nowadays, several groups of biological drugs are being used for psoriasis treatment. Although these therapies are very effective, they show significant variability in efficacy among individuals. Therefore, there is a need for biomarkers to predict treatment outcomes in order to guide personalized therapeutic decisions. Pharmacogenetics is the study of variations in DNA sequences related to drug response. Materials and Methods: In this article, we review pharmacogenetics studies on the treatment of moderate-to-severe psoriasis focusing on anti-interleukin (IL) 12/23 (ustekinumab) and anti-IL17 drugs (secukinumab and ixekizumab), as well as recent studies concerning anti-TNF drugs. Results: Several polymorphisms have been studied over the years in reference to anti-TNF drugs; some of the most recent studies included the performance of a genome-wide association study (GWAS) and pharmacogenetics studies focused on the optimization of a treatment regimen. Various polymorphisms in different genes have been related to ustekinumab response; among them, the most commonly studied is the HLA-C*06:02 allele. Conclusions: Although not confirmed in some studies, most studies have shown that patients carrying this allele present a significantly higher response rate to ustekinumab. Some polymorphisms have been studied in patients treated with anti-IL17 drugs, mostly related to secukinumab; however, up to now, no association has been found between any of these polymorphisms and response. Nevertheless, further studies involving larger cohorts are needed in order to confirm these results before the implementation of this biomarker in clinical practice.

POLYMORPHISMS OF ENDOTHELIAL DYSFUNCTION GENES NOS3 AND CYBA IN YAKUT POPULATION

Polymorphisms of different genes can predispose people to various diseases. They can influence the body's physiological response to exogenous risk factors. Polymorphisms of the endothelial dysfunction genes NOS3 and CYBA contribute to the development of socially significant diseases, such as acute coronary syndrome, stroke, as well as diseases accompanied by fibrotic changes (cirrhosis of the liver, pulmonary fibrosis, etc.). Therefore, the study of these genes in the Yakut population seems relevant. The present study involved 124 healthy volunteers, their ethnicity is Yakuts (including Yakuts in the third generation, living in the Republic of Sakha (Yakutia)). Genetic analysis of polymorphisms was performed by the method of polymerase chain reaction of restriction fragment length polymorphisms (PCR-RFLP). The study found that healthy Yakuts have GG homozygote of rs1799983 of the NOS3 gene in 83.87%, GT - 15.32%, TT - 0.81%. The frequency of the G allele was 91.53%, the T allele - 8.47%. The study found that healthy Yakuts have CC homozygote of rs4673 of the CYBA gene in 75.0%, CT - 21.77%, TT - 3.23%. The frequency of C allele was 91.44%, T - 8.56%. These results are consistent with the literature data. Thus, the research of the polymorphism rs1799983 of the NOS3 gene and rs4673 of the CYBA gene in various ethnic groups could have encouraging prospects in the personalized medicine for predicting pathological conditions associated with endothelial dysfunction: liver fibrosis, cardiovascular diseases, obstetric and gynecological pathologies, dysfunctions of various organs and systems.

TRAILR1 (rs20576) and GRIA3 (rs12557782) are not associated with interferon-β response in multiple sclerosis patients.

Multiple sclerosis (MS) is an autoimmune-type inflammatory disorder in human central nervous system. Recombinant interferon beta (IFN-β) decreases the number of relapses and postpones disability progression in MS. However, up to 50% of patients treated with interferon beta continue experiencing relapses and/or worsening disability. Single nucleotide polymorphisms in different genes have been known to show significant associations with response to IFN-β in MS patients. In the present work, we examined the potential role of TRAILR1 and GRIA3 genes polymorphisms on response to IFN-β therapy in Iranian MS patients. The DNA was extracted from blood samples by standard procedures from 73 patients diagnosed with Multiple Sclerosis that were either responded to IFN-β or did not. We carried out RFLP -PCR and tetra-primer ARMS-PCR methods to study of rs20576 and rs12557782, respectively. All results were analyzed using the SPSS software. TRAILR1 rs20576 genotype frequencies in responders and non-responders were similar (χ2 = 0.26, P = 0.87, Fisher, s Exact test). Our results showed that response to IFN-β has not association with sex (p = 0.73). Also, genotypic frequencies of GRIA3 rs12557782 had no significant differences between two groups of female population (χ2 = 3.75, p = 0.15). Furthermore, it had not been any statistical differences between responder and non-responder males (χ2 = 0.7, p = 0.4) related to the SNP. Our results analysis revealed no significant association between the studied SNPs (TRAILR1 rs20576 and GRIA3rs 12,557,782) and response to IFN-β in Iranian MS patients.

Are the genes CA6, TAS2R38, TCF7L2, FTO, TAS1R2, TAS1R3, GNAT3 receptor polymorphisms involved on exceptional longevity and risk of sarcopenia? A cross sectional study in Italian aging population

This study hypothesized that genetic polymorphisms of different genes could modulate the lifespan and muscle health or sarcopenia. We investigated the possible associations between longevity and the common genetic variation polymorphism such as rs713598, rs7903146, rs9939609, rs35874116, rs2274333, rs7792845, rs35744813 in a population of 360 Italian elderly aged 65- 100 years. The polymorphism rs9939609, of the FTO gene, shows an association (p< 0.001) with longevity. In particular, the frequency of T/T homozygotes increases gradually from 35% in subjects aged 65-80 ys up to 80% in centenarians. The polymorphism of rs2274333 (CA6) gene shows that A/G frequency increases continuously through older classes reaching the 80% in (95-100) (p trend <0.05). Another important founding regards the polymorphism of rs35744813 of TAS1R3 gene. The C/C genotype frequency is over 80% in all classes (65-95 years) but appears increase in oldest old and reach 100% (95-100 ys). While T allele frequency decrease continuously through older classes reaching the 0% in T/T and 5% in C/T in (95-100) (p-trend <0.05). These data provide suggestive evidence on the possible correlation between longevity and FTO gene (obesity related), CA6 gene (the gustin- bitter taste related) and TAS1R3 (umami taste stimulus related). None associations with sarcopenia were detected.

Genetic risk factors of Alzheimer’s disease

Introduction. Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases, which is a serious health problem for societies that live longer. Spontaneous dominant mutations and polymorphisms of selected genes play an important role in development of AD. Aim. Several polymorphisms in selected genes strongly associated with development of Alzheimer’s disease were highlighted in this review: APOE, CYP46, APP, PSEN1, PSEN2, UBQLN1, BACE1, PRND, APBB2, TOMM 40. These gene polymorphisms have a significant role in the development of Alzheimer’s disease and they have potential to be biomarkers. Researchers combine efforts to find significant polymorphisms that would ensure that a person is predisposed to the occurrence of disease symptoms. This topic is often taken up by scientists seeking to develop effective genetic tests for diagnosing AD. Material and methods. Analysis of literature from web of knowledge: Web of Science (all database), NCBI and PubMed. Results. We reviewed the selected important genes and polymorphisms which are most often associated with development of AD. Conclusion. It should be noted that nowadays scientists strive not to focus on only one polymorphism in the gene but on several polymorphisms in different genes concomitantly and above all on interactions between them to the diagnosis of this disease. Only this approach to AD will contribute to the creation of appropriate identification methods. Moreover, we should use the new generation tools - the platform for collecting data and personalized medicine.

Host genetics and tuberculosis: Theory of genetic polymorphism and tuberculosis.

Background and Objective:Tuberculosis (TB), the leading cause of morbidity and mortality by a single infectious agent, Mycobacterium tuberculosis, is still a major health problem in the world. To date, many studies have shown evidence of association between host genetic polymorphisms and TB susceptibility, including chemokine (C-C motif) ligand 2 (CCL-2)/monocyte chemoattractant protein1 (MCP-1), natural resistance-associated macrophage protein 1 (NRAMP-1)/solute carrier protein 11A1 (SLC11A1), Immunity-related GTPase family M protein (IRGMI), interleukin (IL)-8, toll-like receptor (TLR), and nucleotide-binding oligomerization domain containing protein-2 (NOD-2) genes. Most of these genes participate in immune response, and their polymorphism can alter immunity and lead to genetic susceptibility to TB.Materials and Methods:This is a special article compiled with reference to various case-control studies, meta-analysis, and other research work on different genes and TB. The genes selected and a number of studies from different countries and ethnic groups for this article are shown below. The genes selected for the study are: NRAMP-1 (SLC11 A1), Vitamin D receptor, low molecular weight polypeptide/transporter with antigen processing, CCL-2/MCP-1, IRGM-1, IL-1, IL-8, IL-10, IL-12, TLR, NOD-2, human leukocyte antigen, mannose-binding lectin, major histocompatibility complex, tumor necrosis factor, P2X 7, epiregulin, SP110, and interferon gamma (IFN-gamma).Results:Genetic polymorphisms in different genes showed variable levels of significance in relation to TB. All these were proved by the researchers using appropriate statistical methods and tools.Conclusions:Based on different research works across the world, there is sufficient evidence to prove that TB is a genetically primed and determined infectious disease caused by M. tuberculosis and the genetic polymorphism is the mechanism that leads to progression from infection to TB disease. Why only 10–15% of the people infected with M. tuberculosis progress toward TB disease has continued to be an unresolved debate. Hence, for provoking thoughts and encouraging more research in the field of genetics and TB I formulated hypothesis and algorithms, and theory. Genetic susceptibility to TB has been substantiated based on the extensive literature review and the research findings that are well narrated.

Genetic variation in bone morphogenetic proteins family members (BMPs 2 and 4) and hypertension risk in middle-aged men

Bone morphogenetic proteins (BMPs) are important regulators of iron metabolism affecting hepcidin expression. We have previously shown that 2 genetic polymorphisms in different genes (histocompatibility complex class I-like transmembrane protein, hemojuvelin) involved in the regulation of hepcidin expression pathways are associated with hypertension. In this study, we analyzed genetic variation sites in BMP2 (rs235756, rs235768) and BMP4 (rs4901474) to get more evidence linking iron metabolism to hypertension risk in the Finnish population.The study included 321 hypertensive cases and 463 controls from the Tampere Adult Population Cardiovascular Risk study cohort. Genotyping of polymorphisms was done by polymerase chain reaction using DNAs extracted from buccal swabs.We found that men carrying the GG genotype of BMP2 rs235756 (A>G) polymorphic site had a 4.09-fold risk (confidence interval [CI] 1.61–10.39, P = .003) for hypertension at the age of 50 years compared with A-allele carriers. The risk was significant in the age groups of 45 and 40 years as well. In addition, the 15-year follow-up period of the same individuals showed that carriers of the GG-genotype had also significantly higher readings of both systolic (P < .001) and diastolic (P = .01) blood pressure during the follow-up time. No significant association between BMP2 rs235768 (A>T) and hypertension was found. BMP4 polymorphic site rs4901474 (T>C) also had an effect on hypertension. CC genotype carriers had a 1.48-fold risk (CI 1.03–2.13, P = .033) for hypertension at the age of 50 years when compared with T-allele carriers.In conclusion, BMP2 polymorphic site rs235756 was associated with hypertension in Finnish men. An effect of BMP4 polymorphic site on hypertension was also found.

Genetic Perspective of Hepatocellular Carcinoma (HCC) in Asian population - A Review

Hepatocellular Carcinoma (HCC) is the fifth most common cancer which causes thousands of death worldwide and the majority of the HCC sufferers are from Asia. Infection of Hepatitis B Virus and Hepatitis C Virus are major reasons for the development of HCC. The factors which add to its persistence are both environmental and genetic. Asia being a vast continent has a huge diversity of both. Polymorphisms in different genes linked with HCC lead to either increase or decrease in its risk. In this review we have focused on genetic factors responsible for HCC, with a special perspective based on the geography. According to the UN geo-scheme Asia is split into Eastern, Southeastern, Southern, Western and Central Asia. Here we have discussed on various genetic mutations which may or may not be the risk factor for HCC. The maximum HCC linked genetic mutations were observed in the Eastern region especially in China. *

Association Analysis of Polymorphisms in TOMM40, CR1, PVRL2, SORL1, PICALM, and 14q32.13 Regions in Colombian Alzheimer Disease Patients.

We evaluated the association of several single-nucleotide polymorphisms in different genes including APOE, TOMM40, CR1, PVRL2, SORL1, PICALM, and GWA_14q32.13 in a Colombian sample of Late-Onset Alzheimer disease (LOAD) patients. A case-control study was conducted in 362 individuals (181 LOADs and 181 controls) to determine the association of single-nucleotide polymorphisms in APOE (e2, e3, and e4), TOMM40 (rs2075650), CR1 (rs665640), PVRL2 (rs6859), SORL1 (rs11218304), PICALM (rs3851179), and GWA_14q32.13 (rs11622883) with LOAD in a sample from Colombia. We were able to confirm the previously reported association of the APOE4 allele with AD. In addition, we report a new significant association with rs2075650 of TOMM40 for LOAD in our sample. We did not detect any significant interaction between TOMM40 and APOE4 carriers (heterozygous or homozygous) for disease risk development. However, Kaplan-Meier survival analyses suggest that AD patients with TOMM40 allele rs2075650-G have an average age of disease onset of 6 years earlier compared with carriers of the A allele. In addition, the age of disease onset is earlier if APOE4/4 is present. Our findings suggest that rs2075650 of TOMM40 could be involved in earlier presentation of LOAD in the Colombian population.

The TYMS-TSER polymorphism is associated with toxicity of low-dose capecitabine in patients with advanced gastrointestinal cancer.

Low doses of drugs delivered at close, regular intervals are increasingly being used to manage patients with different neoplasms. Despite the good tolerability, treatment-related adverse events still occur following metronomic protocols. The aim of this study was to retrospectively investigate whether polymorphisms of different genes involved in fluoropyrimidine metabolism and 5-fluorouracil (5-FU) degradation rate were associated with the outcome of a low-dose capecitabine schedule. Genotyping of DPYD IVS14+1 G>A, MTHFR C677T, and A1298C single-nucleotide polymorphisms was performed by pyrosequencing technology. A PCR technique was used for genotyping TYMS-TSER. Using peripheral blood mononuclear cells, we also evaluated the 5-FU degradation rate, which determines the net result of all the enzymatic transformation of 5-FU, in terms of the amount of drug consumed by the cells in a time unit. The association of these variables with clinical outcome was evaluated using multivariate logistic regression analysis. Eighty-four patients with metastatic gastrointestinal cancer, who had been treated with a low-dose fluoropyrimidine schedule, as a rescue therapy were included in the study. The TSER 2R/2R genotype was significantly associated with both hematologic (odds ratio=7.90, P=0.002) and gastrointestinal toxicity (odds ratio=3.24, P=0.009). Because DPYD IVS14 G>A single-nucleotide polymorphism was not observed in the cohort, it was excluded from the statistical analysis. No significant association was detected between clinical outcome and both MTHFR polymorphisms and the 5-FU degradation rate. In the advanced setting of cancer care, high attention should be paid toward avoiding toxicity and worsening of quality of life. Although metronomic chemotherapy is generally well tolerated, treatment toxicity nonetheless does occur. Our data suggest a possible role of the TSER 2R/2R polymorphism as a predictive marker of toxicity in patients treated with low-dose capecitabine.

GENETIC PREDICTORS OF ATRIAL FIBRILLATION

Atrial fibrillation (AF) is the most common heart rhythm disturbance. It is believed that the primary form of AF is genetically determined in most cases, but the genetic component cannot be excluded in the secondary form of AF. AF is a heterogeneous disease and many authors proved its relationship with other genetic heart disease. In most cases, certain combinations of polymorphisms of different genes promote the development of AF. The study of genes of renin-angiotensin-aldosterone system (RAAS) is especially important, because the role of this system in AF pathogenesis is currently studding most intensively. These studies are of great practical interest, as associative effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in the prevention of AF is revealed. RAAS blockers are able not only to reduce the risk of new-onset AF in hypertensive and normotensive patients but also prevent recurrence of AF. Furthermore, experimental studies showed that RAAS blockers prevent not only the remodeling of the left ventricle, and also the left atrium, pointing to the pathogenesis of AF. So, screening for susceptibility genes and the study of their polymorphism is currently an important focus in the study of AF.

Association Between Combined Presence of Hepatitis C Virus and Polymorphisms in Different Genes With Toxicities of Methotrexate and 6-Mercaptopurine in Children With Acute Lymphoblastic Leukemia.

The aim of the present study is to determine the correlation of hepatitis C virus (HCV) infection and polymorphisms in different genes with toxicity of either methotrexate (MTX) or 6-mercaptopurine (6-MP) administered to children with acute lymphoblastic leukemia (ALL). One hundred children with low-risk ALL, who were treated according to the St. Jude Total therapy XV, were recruited. The recruited children were receiving MTX and 6-MP during maintenance phase. Patients were excluded from the study if they had other types of leukemia. Genotyping analyses for the thiopurine methyltransferase (TPMT), methylenetetrahydrofolate reductase (MTHFR), and glutathione S-transferase (GST) genes were performed using a combination of polymerase chain reaction (PCR) and PCR-RFLP (where RFLP is restriction fragment length polymorphism) protocols. Relevant clinical data on adverse drug reactions were collected objectively (blinded to genotypes) from the patient medical records. There was a significant correlation between the combined presence of HCV and TPMT*3B G460A gene polymorphisms and grades 2-4 hepatotoxicity as aspartate aminotransferase (AST) elevation (P < 0.04). The same observation was seen when comparing either the presence of HCV alone or the presence of the gene polymorphism alone. A significant association between the combined presence of HCV and MTHFR C677T polymorphism and grades 2-4 hepatotoxicity as alanine aminotransferase (ALT), AST, and alkaline phosphatase (ALP) elevation was observed (P values <0.001, 0.02, and 0.001, respectively). The presence of HCV infection had a significant negative effect on hepatic transaminases. The present data support a role for combining analysis of genetic variation in drug-metabolizing enzymes and the presence of HCV in the assessment of specific drugs toxicities in multiagent chemotherapeutic treatment regimens.

Association between Gene Polymorphisms and Pain Sensitivity Assessed in a Multi-Modal Multi-Tissue Human Experimental Model - An Explorative Study.

The genetic influence on sensitivity to noxious stimuli (pain sensitivity) remains controversial and needs further investigation. In the present study, the possible influence of polymorphisms in three opioid receptor (OPRM, OPRD and OPRK) genes and the catechol-O-methyltransferase (COMT) gene on pain sensitivity in healthy participants was investigated. Catechol-O-methyltransferase has an indirect effect on the mu opioid receptor by changing its activity through an altered endogenous ligand effect. Blood samples for genetic analysis were withdrawn in a multi-modal and multi-tissue experimental pain model in 40 healthy participants aged 20-65. Seventeen different single nucleotide polymorphisms in different genes (OPRM, OPRK, OPRD and COMT) were included in the analysis. Experimental pain tests included thermal skin stimulation, mechanical muscle and bone stimulation and mechanical, electrical and thermal visceral stimulations. A cold pressor test was also conducted. DNA was available from 38 of 40 participants. Compared to non-carriers of the COMT rs4680A allele, carriers reported higher bone pressure pain tolerance threshold (i.e. less pain) by up to 23.8% (p < 0.015). Additionally, carriers of the C allele (CC/CT) of OPRK rs6473799 reported a 30.4% higher mechanical visceral pain tolerance threshold than non-carriers (TT; p < 0.019). For the other polymorphisms and stimulations, no associations were found (all p > 0.05). In conclusion, COMT rs4680 and OPRK rs6473799 polymorphisms seem to be associated with pain sensitivity. Thus, the findings support a possible genetic influence on pain sensitivity.

Association between Vascular Endothelial Growth Factor Polymorphisms and Age-Related Macular Degeneration: An Updated Meta-Analysis.

Age-related macular degeneration (AMD) is the most common cause of blindness in elderly people worldwide and the major degenerative disease of the retina that leads to progressive impairment of central vision. Several polymorphisms in different genes have been proposed as factors that increase the disease susceptibility. The aim of the present study is to carry out a systematic review and an updated meta-analysis in order to summarize the current published studies and to evaluate the associations between four common vascular endothelial growth factor (VEGF) polymorphisms (rs833061, rs1413711, rs3025039, and rs2010963) and AMD risk, also stratifying for AMD subtypes and ethnicity. A systematic literature search in the Medline database, using PubMed, was carried out for epidemiological studies, published before June 2016. Associations of VEGF polymorphisms with AMD were estimated by calculating pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) based on different models. Twelve articles were included in the analysis. The present meta-analysis constitutes a useful guide for readers to study AMD and adds new evidence to the growing literature on the role of VEGF polymorphisms in the risk of AMD. Significant associations with AMD risk were showed for rs833061, rs1413711, and rs3025039 polymorphisms but not for rs2010963.

Genetic polymorphisms of CYP3A4 1B of cervical cancer patients in Bangladeshi population, Bangladesh

Background: Cervical cancer incidence rate in Bangladesh is 15.9 and age-standardized incidence rate is 19.2 (rates per 1,00,000 women per year). Polymorphisms of different genes have been affirmed to be associated with cervical cancer. Our prime purpose is to observe whether CYP3A4*1B polymorphisms are related with increasing cervical cancer risk in Bangladeshi population. The compilation of precise clinical information allows the clarity of different clinical phenotypes, which play a vital role in genetic studies of cervical cancer. Methods: The study was a case-control study carried out between patients and volunteers matched by age, sex, height, weight and smoking status. Daly’s chemical method was used to isolate genomic DNA from venous blood. The demographic variables of cases and controls were put side by side using chi-square tests and Student’s t tests. Results: Odds ratio and 95 % confidence interval were assigned to estimate the risk of cervical cancer. CYP3A4*1B polymorphisms and cervical cancer risk do not show any considerable relationship. The polymorphic frequencies of CYP3A4*1B allele (normal homozygote, heterozygote and mutant homozygote ) in cervical cancer were 60%, 40% and 0% respectively; frequencies in control were 66.67%, 33.33% and 0% respectively (p<0.05). Finally, we conclude that CYP3A4*1B polymorphisms is not associated in susceptibility to developing cervical cancer, at least in Bangladeshi population. Conclusions: In brief, the consequences of our study demonstrated that CYP3A4*1B polymorphism is not allied in susceptibility to develop cervical cancer, at least in Bangladeshi women.

Association of VDR FokI and ApaI genetic polymorphisms with parkinson's disease risk in South Western Iranian population

Background: Parkinson's disease comes second comparing to Alzheimer's disease being responsible for nerve destructing diseases; it is a complex and multifactorial disease. Gene associated studies help to identify the genetic factors that introduce the Single Nucleotide Polymorphisms in different genes as genetic risk factors for non-Mendelian Parkinson's disease in diverse populations. We intended to study the association of VDR (Vitamin D Receptor) gene polymorphisms with Parkinson's disease in south western Iranian population. Results: In the present study 150 patients with Parkinson's disease and 160 Healthy controls from an Iranian population were genotyped for two polymorphic sites. The prevalence of VDR polymorphisms in two restriction fragment length polymorphism sites including FokI and ApaI were analyzed in patients and controls. Our data demonstrated no significant association between VDR FokI polymorphism and PD, whereas the ApaI polymorphism showed a significant association with PD in Iranian patient. Also no association between the age at onset, the male-female ratio and the VDR polymorphism in the PD group was detected. Conclusions: In conclusion these results determined that VDR ApaI (TG and GG) genotype might affect development of PD in our study population. There was no association between FokI polymorphism and the risk of PD. Our results were analogous only with American/Hungarian Caucasian race.