Rs1799983 Polymorphism Research Articles

Clinical Relevance of VEGFA (rs3025039) +936 C>T Polymorphism in Primary Myelofibrosis: Susceptibility, Clinical Co-Variates, and Outcomes.

We evaluated the association of VEGFA rs3025039 polymorphism with clinical co-variates and outcomes in 849 subjects with primary myelofibrosis (PMF) and 250 healthy controls. Minor T-allele frequency was higher in subjects with JAK2V617F compared with those without JAK2V617F (18% vs. 13%; p = 0.014). In subjects with JAK2V617F, the TT genotype was associated at diagnosis with lower platelet concentrations (p = 0.033), higher plasma LDH concentration (p = 0.005), higher blood CD34-positive cells (p = 0.027), lower plasma cholesterol concentration (p = 0.046), and higher concentration of high-sensitivity C-reactive protein (p = 0.018). These associations were not found in subjects with PMF without JAK2V617F. In subjects with the TT genotype, risk of death was higher compared with subjects with CC/CT genotypes (HR = 2.12 [1.03, 4.35], p = 0.041). Finally, the TT genotype was associated with higher frequency of deep vein thrombosis in typical sites (12.5% vs. 2.5%; OR = 5.46 [1.51, 19.7], p = 0.009). In conclusion, in subjects with PMF, the VEGFA rs3025039 CT or TT genotypes are more common in those with JAK2V617F than in those without JAK2V67F mutation and are associated with disease severity, poor prognosis, and risk of deep vein thrombosis.

APOA-5 Genetic Variant rs662799: Role in Lipid Changes and Insulin Resistance after a Mediterranean Diet in Caucasian Obese Subjects.

Background and Aims This APOA5-1131C allele is related with a higher serum triglyceride levels and perhaps a different metabolic response to a dietary intervention. The aim of the present investigation was to evaluate SNP rs662799 in the APOA5 gene and its associations with metabolic effects after a hypocaloric diet with Mediterranean pattern. Methods A population of 363 Caucasian obese patients was enrolled. Anthropometric parameters and serum parameters (lipid profile, insulin, homeostasis model assessment (HOMA-IR), glucose, C reactive protein, adiponectin, resistin, and leptin levels) were measured, at basal time and after 3 months. All patients were genotyped in the rs662799 polymorphism. Results The APOA5 variant distribution was as follows: 89.3% (n = 324) (TT) were homozygous for the T allele, 10.5% (n = 38) (TC) were heterozygous, and 0.2% (n = 1) (CC) were homozygous for the C allele. Triglyceride levels were higher in patients with the C allele. After dietary intervention, BMI, weight, fat mass, waist circumference, systolic blood pressure, adiponectin, leptin, and adiponectin/leptin ratio improved significantly in both genotype groups TT and TC+CC. After dietary intervention, insulin levels (delta: −3.6 ± 0.8 UI/L vs. −1.5 ± 0.6 UI/L; P = 0.03), HOMA-IR (delta: −1.5 ± 0.4 units vs. −0.3 ± 0.2 units; P = 0.02), and triglyceride levels (delta: −19.3 ± 4.2 mg/dL vs. −3.2 ± 3.1 mg/dL; P = 0.02) decreased in non-C allele carriers. Conclusions C allele carriers of rs662799 of the APOA5 gene did not show an improvement in triglyceride, insulin, and HOMA-IR levels after a significant weight loss due to a hypocaloric diet with a Mediterranean pattern.

Association between eNOS rs1799983 polymorphism and hypertension: a meta-analysis involving 14,185 cases and 13,407 controls

BackgroundEssential hypertension is a complex disease determined by the interaction of genetic and environmental factors, eNOS is considered to be one of the susceptible genes for hypertension. Our study aimed to evaluate the association between eNOS rs1799983 polymorphism and hypertension, and to provide evidence for the etiology of hypertension.MethodsCase–control studies of eNOS rs1799983 polymorphism and hypertension were included by searching PubMed, Embase, Web of Science, Medline, Scopus, WanFang datebase, Vip datebase, and CNKI database according to PRISMA guideline. Eligible data were extracted and pooled, and were analyzed using R software based on five different genetic models.ResultsA total of 60 eligible articles involving 14,185 cases and 13,407 controls were finally selected. We found significant association between eNOS rs1799983 polymorphism and hypertension under any genetic model (T vs G: OR = 1.44, 95% CI 1.26–1.63; GT vs GG: OR 1.34, 95% CI 1.18–1.52; TT vs GG: OR 1.80, 95% CI 1.41–2.31; GT + TT vs GG: OR 1.42, 95% CI 1.25–1.63; TT vs GG + GT: OR 1.68, 95% CI 1.35–2.08; GT vs GG + TT: OR 1.24, 95% CI 1.11–1.40).ConclusionsWe found that eNOS rs1799983 polymorphism is associated with the increased risk of hypertension under any genetic model. Moreover, investigations of gene–gene and gene-environment interactions are needed to give more insight into the association between eNOS rs1799983 polymorphism and hypertension.

Association of PON1, LEP and LEPR Polymorphisms with Susceptibility to Breast Cancer: A Meta-Analysis.

Objective:Breast cancer is the most common cancer in American women, except for skin cancers. In this meta-analysis, the associations of polymorphisms within paraoxonase 1 (PON1), leptin (LEP) and leptin receptor (LEPR) genes with susceptibility to breast cancer were comprehensively evaluated. Methods:A universal search in PubMed, Scopus, CNKI, SID, Web of Knowledge and Google Scholar was performed to identify relevant studies up to 01 May, 2021. The strength of the associations was estimated by Odds ratios (ORs) with 95% confidence intervals (95% CIs). Results:A total of 39 case-control studies including 7 studies with 2005 cases and 2748 controls were on PON1 rs662, 6 studies with 2,031 cases and 1,973 controls on PON1 rs854560, 12 studies with 3,444 cases and 3,583 controls on LEP rs7799039, and 14 studies with 5,330 cases and 6,188 controls on LEPR rs1137101 were selected. Pooled data showed that PON1 rs662 and rs854560 polymorphisms were associated with risk of breast cancer in overall population, but not LEP rs7799039 and LEPR rs1137101. Conclusions:Our pooled data revealed that the PON1 rs662 and rs854560 polymorphisms were significantly associated with an increased risk of breast cancer in the overall population. However, LEP rs7799039 and LEPR rs1137101 polymorphisms were not associated.

PCSK9 Gene Polymorphisms Associated With the Risk of Myocardial Infarction in Iranian Patients

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulatory protein in lipid metabolism and a candidate gene in the etiology of cardiovascular diseases. The present study aimed to evaluate the prevalence and significance of PCSK9 rs505151 and rs11591147 variants with myocardial infarction (MI) risk in the Iranian population. Patients and Methods: The frequency of the PCSK9 rs505151 and rs11591147 variants were compared between 600 cases of MI and 600 healthy age- and sex-matched individuals. Tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS PCR) was used for rs505151, and amplification refractory mutation system-polymerase chain (ARMS-PCR) was utilized to detect the rs11591147 polymorphism. Finally, SPSS and SHEsis software were applied for data analysis. Results: Carriers of the GG genotype of rs505151 polymorphism (OR: 1.57, 95% CI: 1.05–2.35, P = 0.02; age-adjusted; OR: 1.54, 95% CI: 1.03–2.32, P = 0.03) and at least one G-allele including GG+AG vs. AA (OR: 1.54, 95% CI: 1.04–2.28, P = 0.03; age-adjusted; OR: 1.51, 95% CI: 1.01–2.24, P = 0.04) have an increased risk of MI. No association between PCSK9 rs505151 alleles and MI risk was observed. The ratio of individuals with the rs11591147GT variant was higher in healthy individuals vs. patients with MI (48.6% vs. 41.7%), indicating a reduced risk of developing MI (OR: 0.75; 95% CI: 0.59–0.95; P = 0.01; age-adjusted; OR: 0.74; 95% CI: 0.58–0.95; P = 0.01). The carriers of at least one T allele (TT+GT vs. GG) (OR: 0.78; 95% CI: 0.62–0.98; P = 0.03; age-adjusted; OR: 0.78; 95% CI: 0.62–0.98; P = 0.03) showed a significant reduction in MI risk. The allelic frequencies at this polymorphic site did not differ between MI patients and healthy counterparts. No association was found between the haplotypes constructed from the alleles of these two polymorphisms. Conclusion: Our study provides the first evidence that PCSK9 gene polymorphisms may serve as independent prognostic markers for MI patients in Iran.

Interrelation between the rs2200733 polymorphism of the ATFB5 gene and atrial fibrillation in Uzbek patients.

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias and a major predictor of morbidity and mortality. AF is a polygenic and polyetiological disease. In various ethnic groups, the strongest and most independent relationship with the development of AF was found with the 4q25 locus, where the ATFB5 gene is located. An analysis of the literature data showed that the carriage of the TT genotype of the rs2200733 ATFB5 gene polymorphism is the most unfavorable genotype for the development of AF. The purpose of the study was to identify the prevalence of genotypes and alleles of the rs2200733 polymorphism of the ATFB5 gene in Uzbek patients with AF. The study included 69 Uzbek patients with paroxysmal (n=20) and persistent AF (n=49). The control group (n=30) was composed of Uzbek patients without AF. Genotyping for the carriage of allelic variants of the rs2200733 polymorphism of the ATFB5 gene was performed using the Polymerase Chain Reaction-Restriction Length Polymorphism (PCR-RFLP) method. The distribution of the C and T alleles and the CC, CT, and TT genotypes of the rs2200733 polymorphism of the ATFB5 gene in patients with AF and controls were compared. After genotyping 69 patients with AF, the following distribution of the ATFB5 gene polymorphism rs2200733 was revealed: the CC genotype was detected in 35 (50.72%) patients, the CT genotype in 25 (36.23%) patients, and the TT genotype in 9 (13.05%) patients (p<0.001, χ²=22.435). Moreover, the C allele was detected in 95 (68.8%) patients, and the T allele was detected in 43 (31.2%) patients (p<0.001, χ²=37.696). The distribution of genotypes in the control group was as follows: the CC genotype was detected in 17 individuals (56.7%), the CT genotype was detected in 12 individuals (40%), and the TT genotype was detected in 1 individual (3.3%) (p<0.001, χ²=20.100). Moreover, the C allele was detected in 46 (76.7%) patients, and the T allele was detected in 14 (23.3%) patients (p<0.001, χ²=32.033). The TT genotype of the ATFB5 gene was found to be significantly more prevalent in patients with AF than in controls (13.1% vs 3.3%, p=0.0001). The TT genotype of the rs2200733 polymorphism of the ATFB5 gene was found to be significantly more prevalent in Uzbek patients with AF than in controls.

APOA5 Variant rs662799, Role in Cardiovascular Traits and Serum Adipokine Levels in Caucasian Obese Subjects

Background and Aims: This ApoA5-1131C allele of rs662799 variant is related with a higher serum triglyceride levels, and it contributes to increase risk of cardiovascular disease. The aim of the present investigation was to evaluate single nucleotide polymorphism rs662799 in APOA5 gene and its associations with cardiovascular risk factors, MS, and serum adipokine levels. Methods: The study involved a population of 1,002 Caucasian obese subjects. Measurements of body weight, waist circumference, fat mass, arterial blood pressure, blood glucose, C-reactive protein, insulin levels, insulin resistance (HOMA-IR), lipid profile, and adipokines levels were recorded. Genotype of ApoA5 gene polymorphism (rs662799) and prevalence of metabolic syndrome (MS) were evaluated. Results: The distribution of the rs662799 polymorphism in this adult population (n = 1,002) was 88.3% (n = 885) (TT), 11.4% (n = 114) (TC), and 0.3% (n = 3) (CC). No significant differences were found between the 2 genotypes in the anthropometric data, MS, or blood pressure. Triglyceride levels were higher in C-allele carriers (delta total group: 19.7 ± 2.1 mg/dL: p = 0.02) than non C-allele carriers. HDL-cholesterol levels were lower in C-allele carriers (delta total group: −6.7 ± 1.1 mg/dL: p = 0.02) than non C-allele carriers. Adiponectin levels were lower in C-allele carriers (delta total group: −11.6 ± 1.0 mg/dL: p = 0.02) too. In C-allele carriers, logistic regression analysis showed an increased risk of hypertriglyceridemia (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.2–3.4, p = 0.001) and percentage of low-HDL-C (OR = 2.2, 95% CI = 1.3–3.7, p = 0.002) after adjusting by body mass index and age. Conclusions: C-allele carriers of rs662799 of APOA5 gene showed high rates of low levels of HDL and hypertriglyceridemia, with differences in triglyceride, HDL cholesterol, and adiponectin levels in Caucasian obese subjects.

Association between endothelial nitric oxide synthase and the renin-angiotensin-aldosterone system polymorphisms, blood pressure and training status in normotensive/pre-hypertension and hypertensive older adults: a pilot study

ABSTRACT Introduction:Variations in blood pressure (BP) are, in part, genetically determined and some polymorphisms of renin-angiotensin- aldosterone system (RAAS) and synthase of endothelial nitric oxide (eNOS) have been related to hypertension (HT). Conversely, physical exercise is considered a non-pharmacological tool for HT control, treatment, and prevention. Objective: The purpose of this study is to investigate the relationship between eNOS and RAAS polymorphisms, their epistatic interaction, and the respective humoral factors in the BP control in normotensive/pre-hypertension and hypertensive older adults and how this relationship can be modulated by training status (TS) level. Methods:A total of 155 older adults (66.94 ± 6.83 years old) performed the following evaluations: AAHPERD battery test to determine the general functional fitness index (GFFI), systolic and diastolic blood pressure (SBP and DBP), blood collection for DNA extraction, analysis of eNOS gene polymorphisms rs2070744; rs61722009 and rs1799983 and RAAS polymorphisms rs699; rs1799752 and rs5186, and quantification of ACE activity (Fluorimetric Assay) and nitrite concentration (Chemiluminescence Method). Results and Conclusion:Good TS level appears to exert greater influence on SBP for G2 and G3 (G1: 125.79 ± 14.03/ G2: 119.91 ± 11.72/G3: 119.71 ± 10.85) and on NO2 for G3 (G1: 0.42 ± 0.25/ G2: 0.54 ± 0.45/ G3: 0.71 ± 0.52). No associations were observed between eNOS and RAAS polymorphisms, but the epistasis was identified between eNOS polymorphism, rs2070744, and RAAS polymorphism, rs699, revealing a statistically significant interaction (p = .0235) with training score of 0.63, a training test accuracy of 0.61 and a cross-validation consistency of 10/10. This result suggests an increased risk of hypertension.

MMP-2 and MMP-9 Polymorphisms and Preeclampsia Risk in Tunisian Arabs: A Case-Control Study

The abnormal production of matrix metalloproteinases (MMPs), especially MMP-9 and MMP-2, plays a pivotal role in hypertensive disorders of pregnancy, and as such, can influence the development of preeclampsia. These alterations may result from functional genetic polymorphisms in the promoter region of MMP-9 and MMP-2 genes, which modify MMP-9 and MMP-2 expression. We investigated the association of MMP-9 polymorphism rs3918242 (-1562 C>T) and MMP-2 polymorphism rs2285053 (-735 C>T) with the risk of preeclampsia. This case–control study was conducted on 345 women with preeclampsia and 281 age-matched women with normal pregnancies from Tunisian hospitals. Genomic DNA was extracted from whole blood collected at delivery. Genotypes for -1562 C>T and -735 C>T polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). An increased frequency of heterozygous MMP-9 -1562 C/T genotype carriers was observed in women with preeclampsia compared to healthy controls (p = 0.03). In contrast, the MMP-2 -735 C>T polymorphism was not significantly different regarding frequency distribution of the allele and genotype between healthy pregnant women and women with preeclampsia. Our study suggests that the MMP-9 -1562 C/T variant, associated with high MMP-9 production, could be a genetic risk factor for preeclampsia in Tunisian women.

Genetic Association of rs10757278 on Chromosome 9p21 and Coronary Artery Disease in a Saudi Population.

PurposeCoronary artery disease (CAD) is one of the most important leading causes of morbidity and mortality worldwide. Few studies have been carried out in the Saudi population regarding the association of rs10757278 polymorphism with CAD. This study aimed to investigate the association of the rs10757278 polymorphism with CAD in Saudi population.Materials and MethodsIn this case-control study, we recruited 437 patients with CAD and 251 cross-matched healthy controls and performed polymorphism genotyping for rs10757278 using a polymerase chain reaction followed by a restriction fragment length polymorphism analysis.ResultsThe G allele (OR-1.44; 95% CI: 1.15–1.80; p=0.001), as GG (OR-2.13; 95% CI: 1.35–3.36; p=0.0009), in the dominant (OR-1.47; 95% CI: 1.03–2.10; p=0.03) and recessive mode (OR-1.84; 95% CI: 1.26–2.70; p=0.001) of inheritance showed a high-risk association. A disease stratified risk analysis was conducted and comparisons were made using an ANOVA analysis. Diabetes showed a risk association (p=0.001). However, a regression analysis confirmed that for the CAD cases, there was an association between the GG genotype and diabetes (p=0.005).ConclusionThe results of this study suggest that the polymorphism rs10757278 is related to a high risk of CAD in a Saudi population.

Role of VEGF Polymorphisms in the Susceptibility and Severity of Interstitial Lung Disease.

The search for biomarkers that can help to establish an early diagnosis and prognosis of interstitial lung disease (ILD) is of potential interest. VEGF polymorphisms have been implicated in the development of several lung disorders. Consequently, we assessed, for the first time, the role of VEGF polymorphisms in the susceptibility and severity of ILD. A total of 436 Caucasian ILD patients (244 with idiopathic interstitial pneumonias (IIPs) and 192 with non-IIP) and 536 ethnically-matched healthy controls were genotyped for VEGF rs833061, rs1570360, rs2010963, rs3025020, and rs3025039 polymorphisms by TaqMan assays. Pulmonary function tests were collected from all the patients. VEGF serum levels were determined by ELISA in a subgroup of patients. No VEGF genotype, allele, carrier, or haplotype differences were found between ILD patients and controls as well as between IIP and non-IIP patients. However, an association of rs1570360 with IIP in women and also with lung function in IIP patients was found. None of the VEGF polymorphisms were associated with VEGF levels. In conclusion, our results suggest that VEGF does not seem to play a relevant role in ILD, although rs1570360 may influence the severity of ILD in women and a worse outcome in IIP patients.

Glu298Asp (rs1799983) Polymorphism Influences Postprandial Vascular Reactivity and the Insulin Response to Meals of Varying Fat Composition in Postmenopausal Women: Findings from the Randomized, Controlled Dietary Intervention and VAScular function (DIVAS)-2 Study

Previous acute studies suggest the Glu298Asp polymorphism (rs1799983) may influence vascular reactivity in response to long-chain n-3 PUFA intake. However, the effects of this genotype on postprandial vascular function after meals rich in SFAs, n-6 PUFAs, and MUFAs are unclear. This study determined the impact of the Glu298Asp polymorphism on changes in vascular function and cardiometabolic risk biomarkers in response to sequential meals of varying fat composition. In a randomized, double-blind, crossover, acute study, 32 postmenopausal women (mean±SD age: 58±5y; BMI: 25.9±4.1kg/m2) consumed mixed meals (breakfast: 0min, 50g fat; lunch: 330min, 30g fat) containing SFAs, n-6 PUFAs, or MUFAs on 3 occasions. Blood samples for cardiometabolic disease risk markers and real-time measures of vascular reactivity [including flow-mediated dilatation (FMD; primary outcome)] were collected/performed before and regularly for 480min after breakfast. Participants were retrospectively genotyped for the Glu298Asp (rs1799983) polymorphism. Data were analyzed using linear mixed models. For the postprandial %FMD response, a test fat × genotype interaction was observed for the AUC (P=0.019) but not incremental AUC (IAUC), with the AUC being ∼24% greater after MUFA- than after SFA- and n-6 PUFA-rich meals in the Glu298 homozygotes (P≤0.026). Test fat × genotype interactions were also evident for postprandial insulin (P≤0.005), with the MUFA-rich meals demonstrating significantly higher AUC (12.8%/14.9%), IAUC (14.6%/20.0%), and maximum concentration (20.0%/34.5%) than the SFA- and n-6 PUFA-rich meals, respectively, in Asp298 carriers (P<0.05). Genotype did not influence other study outcome measures in response to the test fats. Our findings suggest the Glu298Asp polymorphism may represent a potential determinant of the inter-individual variability in postprandial responsiveness of %FMD and insulin to acute meal fat composition in postmenopausal women. Further studies are required to confirm these observations.This trial was registered at clinicaltrials.gov as NCT02144454.

The role of VEGF rs699947 polymorphism in End-Stage Renal Disease: A preliminary study

Aim: End-Stage Renal Disease (ESRD) is an important public health problem worldwide with an increasing incidence and prevalence. There are many environmental and genetic factors which contribute to the development of ESRD. Vascular endothelial growth factor (VEGF) has been suggested to play an important role in renal pathophysiology. The aim of this study was to determine the probable relation between ESRD and VEGF gene rs699947 polymorphism in Turkish population. Material and Method: Genotyping of rs699947 was carried out in 50 ESRD patients on dialysis treatment and 30 healthy controls, using a Kompetitive Allelic-Specific PCR (KASP) method following DNA isolation. Demographic and clinical characteristics of the patients were recorded. Results: The prevalance of rs699947 AA genotype was found to be higher in the control group, but it was not statistically significant (p&gt;0.05) . Conclusion: Although statistically insignificant, the frequency of AA genotype was higher in the control group compared to the case group, therefore we concluded that AA genotype may be a protective factor for ESRD in Turkish population. However, this conclusion needs to be further verified by future studies performed in larger study groups.

Association of the MMP-3, MMP-9 and MMP-12 gene polymorphisms with COPD risk: a meta-analysis.

Given the evidence that the matrix metalloproteinases (MMPs) play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD), a number of case-control studies have attempted to assess the relationship between genetic polymorphisms in MMP genes and COPD risk. However, reliable measures of these results are lacking. We assessed the published evidence for association of the MMP-3, MMP-9 and MMP-12 polymorphisms with COPD risk using meta-analytic techniques. The odds ratio (OR) and 95% confidence interval (CI) were calculated for each study using fixed or random effect models. A total of 23 case-control studies were included in the meta-analysis. No significant association was observed between the MMP-9 rs3918242 polymorphism and COPD risk in the overall populations under the dominant (T/T + C/T vs. C/C: OR = 1.30, 95% CI: 1.00-1.69, p = 0.054) and allele contrast (T allele vs. C allele: OR = 1.22, 95% CI: 0.97-1.53, p = 0.088) models. However, in sub-group analysis the polymorphism rs3918242 was significant in Asians under the dominant model (T/T + C/T vs. C/C: OR = 1.66, 95% CI: 1.02-2.72, p = 0.043). The results for MMP-12 rs2276109 showed an association with COPD only in mixed populations (G/G + A/G vs. A/A: OR = 1.57, 95% CI: 1.10-2.24, p = 0.013; G allele vs. A allele: OR = 1.52, 95% CI: 1.09-2.14, p = 0.015). We did not find any significant association of the MMP-12 rs652438 and MMP-3 rs35068180 polymorphisms with COPD. The findings of this meta-analysis suggest that there is a risk of COPD associated with the MMP-9 rs3918242 and MMP-12 rs2276109 polymorphisms in certain ethnic groups.

Renalase: Gene polymorphism and its association with hypertension in some diseases

Hypertension is a significant public health problem due to its high prevalence and association with increased risk of cardiovascular disease (CVD), and thus the major cause of death in developed countries. Most of diabetes mellitus and hemodialysis patients are expected to have hypertension and of around 10% of pregnant women have hypertension, which increases preeclampsia; the most important medical problem that threatened the life of maternal and neonatal. Previous studies showed that genetic factors could play an important role in predicting hypertension. Recently, a novel soluble flavin adenine dinucleotide (FAD)-dependent amine oxidase, called renalase, found to decrease blood pressure by degrading catecholamines. It is secreted by the kidney and is found in the heart, small intestine, skeletal muscle, endothelium, and nervous system. Renalase polymorphism of the renalase gene may affect the renalase activity and increase susceptibility to some diseases. This review highlights the structure, function, polymorphisms of renalase, and its association with hypertension in hemodialysis, cardiovascular, preeclampsia, and diabetes mellitus patients. As a conclusion, the rs10887800, rs2576178, and rs2296545 renalase gene polymorphism could thus be a risk factor for hypertension.

Immune system parameters in chronic opisthorchiasis patients related to genes polymorphisms associated with developing ischemic heart disease

The aim of the study was to identify a relationship between gene polymorphisms associated with developing coronary heart disease and pathogenetic features of opisthorchiasis invasion. There were compared laboratory parameters assessing the immune system functioning (lymphocyte immunophenotyping evaluated by flow cytometry, serum immunoglobulin and cytokine concentrations, non-specific resistance indices) in patients with chronic opisthorchiasis (caused by Opisthorchis felineus) of various genotypes with/without mutations in loci associated with predisposition to developing coronary heart disease. It was found that opisthorchiasis invasion leads to altered immune response in patients bearing mutations in genes encoding adenosine monophosphate deaminase 1, hypoxia induced factor 1 alpha, and apolipoprotein E affecting relevant protein functions compared to those without minor alleles. Upon that, patients carrying mutation in the adenosine monophosphate deaminase 1 gene, turned out to have lowered cellular (decreased count of cytotoxic lymphocytes) and humoral immunity (decreased immunoglobulin A level). Patients with opisthorchiasis bearing a rare allele in the hypoxia-induced factor 1 alpha gene were featured with activated adaptive immunity and reduced activation of innate immunity. Moreover, mutated apolipoprotein E gene was coupled to decreased activity of cellular immune response, which exacerbates the course of opisthorchiasis invasion, whereas minor allele of the rs1333049 polymorphism in the cyclin-dependent kinase inhibitor gene results in no significantly altered immune response. Thus, gene-related dysfunction of certain proteins may allow opisthorchiasis invasion to elicit multidirectional changes in immune response, so that approaching the normal range of diverse immune-related parameters during chronic parasitic invasion may not necessarily be interpreted as a “protective” effect exerted by any of gene polymorphisms. The most prominent changes in immune response of patients with chronic opisthorchiasis were detected in case of polymorphism in the factor-induced hypoxia-1 alpha gene. The data obtained suggest that the aforementioned genetic polymorphisms may predispose to manifestation of certain opisthorchiasis clinical forms.

Variants in TNF and NOS3 (eNOS) genes associated with sepsis in adult patients.

Sepsis is a life-threatening condition caused by a dysregulated host response to infections and is a leading cause of death in hospitalized patients. The present study aimed to elucidate the possible association between sepsis and the tumor necrosis factor (TNF) gene -308G/A (rs1800629) polymorphism, as well as endothelial nitric oxide synthase (eNOS, NOS3) gene -786T/C (rs2070744), 4a/4b (27 bp-VNTR in intron 4, rs61722009) and 894G/T (Glu298Asp, rs1799983) polymorphisms. In total, 188 septic adult cases and 188 healthy controls were enrolled. Genomic DNAs from the controls and patients were analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. There were significant associations between the G/G genotype and G allele of the TNF -308G/A (rs1800629) polymorphism in the sepsis group (p < 0.001). The presence of the T/C genotype (p = 0.002) and C allele (p = 0.001) of the -786T/C (rs2070744) was markedly associated with an increased risk of sepsis. However, no significant associations were found with 4a/4b (27 bp-VNTR in intron 4, rs61722009) and 894G/T (Glu298Asp, rs1799983) polymorphisms. Higher 4bGC and lower 4bTT haplotype frequencies were associated with sepsis. Our results strongly suggest that TNF gene (-308G/A, rs1800629) and NOS3 gene -786T/C (rs2070744) polymorphisms may modify individual susceptibility to sepsis in the Turkish population.

How matrix metalloproteinase (MMP)-9 (rs3918242) polymorphism affects MMP-9 serum concentration and associates with autism spectrum disorders: A case-control study in Iranian population

The aim of this project was to evaluate the relationship of matrix metalloproteinase-9 (MMP-9) genetic variation and its serum concentration with autism spectrum disorder (ASD). One hundred ASD and 120 controls were enrolled in this study. Genomic DNA was extracted from blood and MMP-9 polymorphism was determined by polymerase chain reaction restriction fragment length polymorphism and serum levels were measured by enzyme-linked immunosorbent assay. The frequencies of CC, CT, and TT genotypes were 72%, 26%, and 2% in controls and 31%, 57%, and 12% in ASD, respectively. The frequencies of C and T alleles in ASD were 59.5% and 40.5%, and controls were 86% and 14%, respectively. There is a significant increase in serum MMP-9 levels in ASD as compared to controls. We have also shown that TT genotype is significantly associated with increase serum MMP-9 levels in patients (TT, CT, and CC serum levels were 91.77 ± 10.53, 70.66 ± 7.21, and 38.66 ± 5.52 and in controls were 55.55 ± 11.39, 42.66 ± 7.85, and 30.55 ± 6.34 ng/ml, respectively). It is concluded that there is a significant association between rs3918242 MMP-9 polymorphism and its serum concentration with autism. We also suggest that TT genotype is associated with increased MMP9 expression and may be a risk factor for ASD.

Increased prevalence of the CVD-associated ANRIL allele in the Roma/Gypsy population in comparison with the majority Czech population.

Cardiovascular disease (CVD) is a major cause of death around the world, with highest prevalence reported in minority Roma/Gypsy populations living in developed countries. Whether these differences are caused by unhealthy lifestyles or genetic factors remain unknown. The aim of our study was to examine the genotype frequencies of the rs10757274 polymorphism in the 9p.21 locus within ANRIL (antisense non-coding RNA in the INK4 locus), a long non-coding RNA located in the vicinity of the CDKN2A/2B inhibitors loci. ANRIL is understood to be the strongest genetic determinant of CVD in Caucasians. Using PCR-RFLP, we analysed the ANRIL rs10757274 polymorphism in 298 non-Roma (50% male) and 302 Roma/Gypsy (50% male) adult (39.5 ± 15.1 years and 39.2 ± 12.8 years, respectively) subjects. We found that frequencies of the ANRIL GG, GA and AA genotypes were 20.1%, 52.4% and 27.5% in the majority population and 32.9%, 47.9% and 19.2% in Roma/Gypsy subjects, respectively. The distribution of genotypes was deemed significantly different at P < 0.001. Within the Roma/Gypsy population, we detected increased prevalence of the CVD-associated GG genotype. Increased prevalence of CVD among Roma/Gypsies subjects may be significantly linked to genetic background.

Impact of PCSK9, WDR12, CDKN2A, and CXCL12 Polymorphisms in Jordanian Cardiovascular Patients on Warfarin Responsiveness and Sensitivity.

BackgroundThe main objective of this study is sought to determine the impacts of PCSK9, WDR12, CDKN2A, and CXCL12 polymorphisms on warfarin sensitivity and responsiveness in Jordanian cardiovascular patients during the initiation and stabilization phases of therapy.MethodsThis study took place at the anticoagulation clinic at Queen Alia Heart Institute (QAHI) in Jordan. DNA samples were collected from 212 cardiovascular patients and 213 healthy controls. Genomic SNPs genotyping was conducted using the MassARRAY System at the Australian Genome Research Facility.ResultsThis study assessed 10 polymorphisms (rs11206510 within the PCSK9 gene, rs6725887 and rs7582720 within the WDR12 gene, rs4977574, rs10757278, and rs1333049 within the CDKN2A gene, rs2862116, rs7906426, rs1746048, and rs268322 within the CXCL12 gene) in 212 Jordanian cardiovascular patients. Carriers of CDKN2A rs1333049, rs10757278, and PCSK9 rs11206510 polymorphisms had an increased risk of resistance during the initiation phase of warfarin therapy compared to those who do not carry it, or those who are carrying one polymorphism only (P < 0.05), while carriers of CXCL12 rs7906426 polymorphism had similar increased risk but during the stabilization phase of warfarin therapy (P < 0.05).ConclusionCarriers of CXCL12 rs2862116 polymorphism had an increased risk to be warfarin extensive responders compared to those with no or only one polymorphism (P = 0.01). However, the presence of PCSK9 rs11206510 polymorphism affects the warfarin maintenance doses (P ˃ 0.0001).