A1298C Polymorphisms Research Articles

Pregnancy outcomes in patients with MTHFR gene polymorphism: A case series

Aim: Based on the literature, MTHFR polymorphism is common among the general population and is controversial in terms of treatment, as it is poorly associated with pregnancy complications. In this study, we aimed to investigate the relationship between treatment and pregnancy outcomes in patients with MTHFR polymorphism.Methods: The data of 48 patients who were diagnosed with MTHFR C677T and A1298C polymorphism between June 2012 and April 2020 and followed up during their pregnancy were reviewed retrospectively. Demographic and clinical features of patients, pregnancy history, diagnosis, and perinatal complications were examined. Pre- and post-treatment clinical features of the patients were compared.Results: Comparison of pre- and post-treatment pregnancy data of the patients revealed that live birth rates were significantly higher (pre-treatment: 9.4% post-treatment: 68.7%, P=0.001) and abortion rates were significantly lower after treatment (pre-treatment: 81.2%, post-treatment: 32.1%, P=0.001). Pregnancy complications were observed in 9 (18.3%) patients. It was observed that among patients with MTHFR gene mutation, live birth rates increased by 24.12-fold and by 3.76-fold for each year of decrease in the age of conception following treatment. Conclusion: In pregnant women with MTHFR polymorphism, methionine-poor diet and medical treatment had a positive effect on pregnancy outcomes. It was also observed that among those with MTHFR gene polymorphism, young patients with MTHFR A1298C heterozygotes had the best treatment results.

Effects of MTHFR genetic polymorphism on inflammatory protein osteopontin in RA patients: A gender based study in North Indian population

BackgroundRheumatoid arthritis (RA) is a systemic chronic inflammatory disease that ultimately damages bone and cartilage of joints leading to disability. Genetic polymorphism in methylene tetrahydrofolate reductase (MTHFR) gene has been identified as potential marker of susceptibility or disease severity in RA. Risk of RA is three times higher in women than men. Several cytokines and proteins play significant role in synovitis of RA patients. Osteopontin (OPN) is the pro-inflammatory cytokine reported to be associated with synovitis in RA, as it generates T-helper-1 (TH1)-mediated cellular immune response. ObjectiveTo study the impact of MTHFR gene polymorphism on the serum levels of OPN in RA patients and to investigate the cause of greater disease severity in women than men. Patients and methodsThe study included sixty RA patients (eleven men and forty-nine women) from different regions of Uttar Pradesh, North India. OPN was estimated by using enzyme-linked immunosorbent assay and other serological parameters such as Serum glutamic oxaloacetic transaminase (SGOT), Serum glutamic pyruvic transaminase (SGPT), C-reactive protein (CRP), triglycerides (TGA), cholesterol, uric acid, albumin and total protein were estimated using commercially available kits. MTHFR A1298C and C677T polymorphism was genotyped using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) based assays. Disease activity score and health questionnaire was assessed in all patients. ResultsMean age of patients was 44.53 ± 1.59 in women and 46.27 ± 4.22 in men with greater duration of morning stiffness in women than men. There were differences in TJC, SJC and DAS-28 score between men and women. OPN levels were found significantly higher in women than men. Other serological parameters were insignificantly higher in women than men. Genotypic study revealed that MTHFR genotypes are not associated with serum OPN levels. However, the disease activity scores (DAS-28), total joint count (TJC) and swollen joint count (SJC) were significantly associated with 1298CC genotype. Frequency distribution of MTHFR gene between men and women indicates that 1298CC genotype was more frequent in women than men and hence it might be one of the factors to cause disease severity more in women than men. ConclusionA1298C polymorphism is a predictor to the disease severity in RA patients. Patients with homozygous mutant CC genotype have a higher DAS-28 score along with TJC and SJC. The significantly higher OPN levels in female subjects suggest that disease severity is more in women than men. However, other parameters such as SGOT, SGPT, CRP, TGA, creatinine, uric acid, albumin and total protein were higher in women but the change was insignificant.

Influence of plasma methotrexate level and MTHFR genotype in Korean paediatric patients with acute lymphoblastic leukaemia

Whether plasma MTX concentrations and MTHFR C677T and A1298C polymorphisms could be used as a predictor of occurrence of MTX-related toxicities in Korean paediatric patients with acute lymphoblastic leukaemia (ALL) were assessed. HD-MTX related toxicities, MTHFR polymorphisms and MTX plasma concentrations following 337 HD-MTX cycles to 117 children with ALL on maintenance therapy were analyzed. A significantly higher frequency of hyperbilirubinemia (P = 0.0443) and renal toxicity (P = 0.0107) were associated with high MTX concentrations by Fisher’s exact test. Moreover, high MTX concentrations at 24 h, 48, and 72 h were significantly associated with increased frequency of vomiting (P < 0.05) and hyperbilirubinemia (P < 0.05) by Mann-Whitney U test. There was a significantly higher frequency of mucositis in patients with the MTHFR 677 TT genotype (P = 0.0273) and a significantly higher frequency of MTX dose reduction in patients with the 677 TT genotype (P = 0.0217), compared to the CC/CT genotype. Independently, plasma MTX concentrations and MTHFR C677T genotype could be useful markers for tailoring MTX dosing and monitoring adverse effects in childhood ALL HD-MTX therapy in Korean patients.

Association of MTHFR A1298C Polymorphism with Preterm Birth: A Meta-Analysis

Background: A few studies have been conducted to explore the association of MTHFR A1298C (rs1801131) polymorphism with preterm birth risk, the results remain inconsistent. Therefore, we conducted a meta-analysis to derive a more systematic estimation of the association. Method: Relevant studies were searched by PubMed, EMBASE, CNKI, and Google Scholar up to June 2018. The strength of the association of MTHFR A1298C polymorphism with preterm birth was calculated by odds ratios (OR) with 95% confidence interval (95%CI). Results: A total of nine case-control studies with 1,609 cases and 14,981 controls were included. Pooled results showed that there was no significant association between MTHFR A1298C polymorphism and preterm birth risk under all five genetic models in overall. However, in the stratified analysis of ethnicity, a significant association between MTHFR A1298C polymorphism and preterm birth risk was observed in the Asians under four genetic models, i.e., allele (C vs. A: OR = 0.960, 95% CI 0.543-0.871, P = 0.002), heterozygote (CA vs. AA: OR = 0.887, 95% CI 0.024-0.457, P = 0.003), dominant (CC+CA vs. AA: OR = 0.965, 95% CI 0.534 -0.935, P = 0.015) and recessive (CC vs. CA+AA: OR = 0.923, 95% CI 0.026-0491, P = 0.004), but not in Caucasians. Conclusion: This meta-analysis suggested that MTHFR A1298C polymorphism is not associated with preterm birth risk in overall population. However, MTHFR A1298C polymorphism plays an important role in preterm birth development in Asian population.

Влияние полиморфизмов С677Т и А1298С гена MTHFR на репродуктивную функцию мужчин

the distribution of C677T (rs1801133) and A1298C (rs1801131) polymorphisms of the MTHFR gene among infertile and fertile men in the Moscow region and to identify a possible Association of these polymorphisms with the risk of pathospermia. the study included 127 infertile men with different forms of pathospermia and 68 fertile men (with one or more children). Genotyping of polymorphisms (C677T and A1298C) gene MTHFR was performed by real-time polymerase chain reaction (PCR-RV). Analysis of the distribution of MTHFR genotypes (C677T and A1298C) revealed no significant differences in the distribution of genotypes in groups of infertile and fertile men. The frequency of minor allele 1298S in asthenospermia was 52%, in teratospermia was 36% and in men with azzospermia - 33% (2=8.67; p=0.003). To date, there are no published results on the study of the Association of polymorphisms of folate-metabolizing enzyme genes with the development of pathospermia among men in the Moscow region. The results of our study demonstrate that 1298 polymorphism of the MTHFR gene may be involved in the etiology of male infertility in patients of the Moscow region. Comparative analysis of gene and genotype frequencies by the studied polymorphisms in infertile men with different forms of pathospermia showed an associative relationship of allele 1298C of MTHFR gene with the risk of asthenozoospermia (p<0.05).

Methylenetetrahydrofolate reductase polymorphism and capecitabine-induced toxicity in patients with gastric cancer

Purpose: To evaluate the effect of methylenetetrahydrofolate reductase (MTHFR) polymorphism on toxicity in gastric cancer (GC) patients treated with capecitabine.&#x0D; Methods: One hundred and twenty-six GC patients were treated with capecitabine in the study. DNA from GC patients was genotyped for MTHFR A1298C using direct sequencing. Toxicity evaluations were graded. Clinical response was assessed.&#x0D; Results: In 87.3 % of the patients, capecitabine toxicity was observed. As for MTHFR A1298C polymorphism, 55.6 % patients who exhibited it were associated with reduced MTHFR activity. MTHFR A1298C was associated with capecitabine-related toxicity (p = 0.008); in addition, MTHFR A1298C was significantly associated with gastrointestinal toxicity (p = 0.026), but not with other types of toxicity.&#x0D; Conclusion: The findings suggest that MTHFR A1298C may be useful for predicting toxicity in GC patients receiving capecitabine treatment, especially gastrointestinal toxicity.&#x0D; Keywords: MTHFR, Polymorphism, Gastric cancer, Toxicity

Impact of MTHFR C677T and A1298C gene polymorphisms on MTX drug toxicity and efficacy profile of RA patients in North India

ObjectiveTo investigate the effect of two different methylenetetrahydrofolate (MTHFR) gene loci C677T and A1298C polymorphisms on Rheumatoid arthritis (RA) and their association in response to methotrexate (MTX) therapy. Subjects and methods110 individuals (60 RA patients and 50 healthy controls) were enrolled from different regions of north India. MTX drug response was evaluated by questionnaire data analysis, disease activity score (DAS-28) and analysis of hepatic, renal and other serological parameters. MTHFR C677T and A1298C polymorphisms were genotyped using restriction fragment length polymorphism- polymerase chain reaction (RFLP-PCR). Independent t-test was applied to compare the means and ANOVA with Bonferroni correction for multiple comparison of genotypically classified groups. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by applying χ2 test, p-value < .05 was considered significant. ResultsThe study found significant differences in all the serological parameters of controls and RA patients except protein and serum SGPT. Elevated transaminases, triglycerides, cholesterol, creatinine, C-reactive protein (CRP), uric acid and albumin are the indicators of MTX adverse effects along with disease severity. Questionnaire analysis showed loss of appetite, weak digestion, low BMI, and weight loss are common features in all the patients after starting MTX therapy. Significant association was found between 677TT genotype with elevated levels of triglycerides. While other parameters such as SGOT, SGPT, CRP, uric acid and cholesterol were insignificantly higher in patients with 677TT polymorphism. 1298CC polymorphism was associated with high CRP levels and 1298 AC with higher triglycerides along with cholesterol in RA patients. However, in controls, only albumin showed significant association with 1298AA genotype. Association of MTHFR C677T polymorphism was insignificant (677CT- OR: 0.905, 95%CI: 0.355–2.307; 677TT- OR: 1.035, 95%CI: 0.338–3.989; p-value = 1) and A1298C polymorphism was also insignificant (1298AC- OR: 0.562, 95%CI: 0.200–1.575, p-value = .4; & 1298CC- OR: 0.502, 95%CI: 0.146–1.717 with p-value = .403) with RA. ConclusionThe results of this study suggest that none of these alleles are predictive for RA disease susceptibility. However, it has a significant impact on its severity with respect to CRP, triglycerides and cholesterol.

MTHFR, XRCC1 and OGG1 genetic polymorphisms in breast cancer: a case-control study in a population from North Sardinia

BackgroundDespite conflicting results, considerable evidence suggests the association between single nucleotide polymorphisms in MTHFR, XRCC1 and OGG1 genes and, risk of developing breast cancer. Here a case-control study is reported, including 135 breat cancer patients and 112 healthy women, all representative of Northern Sardinian population.MethodsPolymerase chain reaction/restriction fragment length polymorphism method was used to determine the genotypes of five polymorphisms: MTHFR C677T (rs1801133) and A1298C (rs1801131), XRCC1 Arg194Trp (rs1799782) and Arg399Gln (rs25487) and OGG1 Ser326Cys (rs1052133). Allelic, genotypic and haplotype association analyses with disease risk and clinicopathological parameters were performed.ResultsA nominally significant association with breast cancer risk was observed for MTHFR C677T polymorphism heterozygous genotype in the codominant model (OR: 0.57, 95% CI: 0.32–1.00, p = 0.049) and for Cys/Cys genotype of the OGG1 Ser326Cys polymorphism in the recessive model (OR: 0.23, 95% CI: 0.05–1.11, p = 0.0465). No significant differences were found at genotype-level for A1298C polymorphism of the MTHFR gene and Arg194Trp and Arg399Gln of the XRCC1 gene. Furthermore, the OGG1 and XRCC1 rs25487 polymorphisms were nominally associated with PgR, Her2 status and with sporadic breast cancer, respectively.ConclusionsBased on genetic characteristics of individuals included in this study, results suggest that MTHFR CT and OGG1 Cys/Cys genotypes have a protective effect that may have an influence on breast cancer risk in a representative Northern Sardinian population.

MTHFR gene polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis based on 16 studies.

Rheumatoid arthritis (RA) is the most common autoimmune rheumatic disease, in which an epigenetic implication in the disease etiopathogenesis has been noted. Here in this meta-analysis, we attempted to investigate the pooled association of methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms and susceptibility to RA risk. A systematic search was performed in the main databases, including MEDLINE and Scopus to search for studies assessing the association between MTHFR gene C677T and A1298C polymorphisms and the risk of RA prior to December 2019. In this meta-analysis, 15 studies with 2165 patients and 1751 healthy controls for C677T SNP and 14 studies containing 2021 patients and 1760 healthy controls for A1298C SNP were included. A significant positive association between C677T SNP and RA risk was recognized in the dominant, recessive, and allelic model, but not TT and CT genotypes. The results indicated that the risk of RA in African population was increased under all genotype models while these results were repeated in Asian population just for recessive model, allelic model, and TT genotype. Moreover, the analysis of A1298C SNP demonstrated a significant association in overall population according to only the recessive model and CC genotype. Subgroup analysis according to the genotyping method indicated that RFLP-PCR method could impress the results of association between MTHFR gene A1298C and C677T SNPs and RA risk. The outcome of this meta-analysis indicated that MTHFR gene C677T SNP was much possibly be associated with RA risk.

A meta-analysis and meta-regression of association between MTHFR A1298C polymorphism and nonsyndromic cleft lip/palate risk: An evaluation based on five genetic models

The present meta-analysis is intended to assess the association between NSCL/P risk and methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism in case-control studies. The Web of Science, PubMed/Medline, Scopus, and Cochrane Library databases were searched for related articles published by April 2019. Review Manager 5.3 was applied to measure the odds ratios (ORs) with 95% confidence interval (CI) in the analyses assessing the strength of the association between A1298C polymorphism and NSCL/P risk. Results Sixteen studies were involved and analysed in this meta-analysis. Altogether, the reviewed articles included 2677 NSCL/P patients and 3669 controls. The pooled ORs of the allele, homozygote, heterozygote, dominant, and recessive models were 1.11 (95% CI: 0.94, 1.30; P=0.21), 1.14 (95% CI: 0.94, 1.37; P=0.18), 0.98 (95% CI: 0.80, 1.20; P=0.87), 1.03 (95% CI: 0.86, 1.22; P=0.79), and 1.18 (95% CI: 0.99, 1.41; P=0.07), respectively. The analysis did not identify any significant association between the polymorphism and the risk of NSCL/P in any ethnicity or source of controls. This meta-analysis revealed that A1298C polymorphism is not associated with NSCL/P susceptibility, and the subgroup analyses based on ethnicity and the source of cases further confirmed this result.

Genetic polymorphism of renin-angiotensin-aldosterone system in type 2 diabetes and in combination with arterial hypertension among Dagestan inhabitants

BACKGROUND: Type 2 diabetes and arterial hypertension are frequent comorbidities under which activation the renin-angiotensin-aldosterone system is important pathogenetic link. The functional state of the RAAS is genetically determined. Genetic polymorphisms of the RAAS system associated with the development of both type 2 diabetes and arterial hypertension have been identified and mapped. Associations of polymorphic variants of the RAAS genes with type 2 diabetes and arterial hypertension among the inhabitants of Dagestan have not been studied.&#x0D; AIM: Studying the association of the most relevant polymorphic variants of the C521T and T704C AGT gene, as well as the A1166C AGTR1 gene with type 2 diabetes and when combining type 2 diabetes with arterial hypertension among Dagestan inhabitants.&#x0D; METHODS: We examined 16 patients with type 2 diabetes, 59 patients with type 2 diabetes combined with arterial hypertension and 51 patients with arterial hypertension, all residents of Dagestan. The control group included 47 healthy persons of the same age group. SNP polymorphisms were investigated by the method of allele-specific Real-Time PCR. The C521T and T704C polymorphisms of the AGT gene and the A1166C polymorphism of the AGTR1 gene were studied.&#x0D; RESULTS: In the group of patients with a combination type 2 diabetes with arterial hypertension, the genotype CT of the C521T polymorphism of the AGT gene is less common compared to the control (23% vs. 43%, 2 = 3,868, p = 0,049), OR score 0,4 (0,2-0,9 ). The situation is similar with the TC genotype of the T704C polymorphism of the AGT gene (39% versus 61%, 2 = 4,282, p = 0,039). OR was 0,4 (0,20,8).On the contrary, in the same patients, but the carriers of the homozygous CC genotype of the T704C polymorphism of the AGT gene, OR exceeded one and made 2.5 (1.02-5.9), the frequency of occurrence was 42% vs. 23%, 2 = 3,363, p = 0,05. The frequency of the mutant allele C of the A1166C polymorphism of the AGTR1 gene in patients with arterial hypertension alone was 31% vs. 14%, 2 = 5.496, p = 0,019, OR 2,5 (1,2-5,0). The frequency of the wild allele A in these same patients was 69% versus 84%, 2 = 5,496, p = 0,019, OR 0,4 (0,2-0,8). A similar situation is determined with the AA genotype (52% versus 73%, 2 = 3,609, p = 0,05), OR = 0,4 (0,1-0,9).&#x0D; CONCLUSIONS: The association of the C521T and T704C polymorphisms, as well as the A1166C candidate genes AGT and AGTR1 with type 2 diabetes and arterial hypertension, is an important component in assessing the susceptibility to the development of these diseases in Dagestan residents.

Associations Between Polymorphisms of Endothelial Nitric Oxide Synthase, Matrix Metalloproteinase 3, Angiotensinogen, and Angiotensin II Type 1 Receptor and Risk of Restenosis After Percutaneous Coronary Intervention: A Meta-analysis

PurposePrevious studies have reported controversial results regarding the risk of restenosis with polymorphisms of endothelial nitric oxide synthase (eNOS), matrix metalloproteinase 3 (MMP-3), angiotensinogen (AGT), and angiotensin II type 1 receptor (AT1R) after percutaneous coronary intervention (PCI). This study aimed to summarize the association between these polymorphisms and risk of restenosis after PCI. MethodsWe searched the electronic databases of PubMed, Embase, Cochrane's Library, and ClinicalTrials.gov for studies on the association of eNOS, MMP-3, AGT, and AT1R polymorphisms with restenosis. FindingsA total of 17 studies (7781 patients) were analyzed, including 5 studies on eNOS G298A (n = 912), 5 studies on MMP3 5A/6A (n = 4519), 6 studies on AGT M235T (n = 1801), and 7 studies on AT1R A1166C (n = 2477). For the G298A variant of the eNOS gene, the allele odds ratio (OR) was 1.685 (95% CI, 1.269–2.338; P < 0.001), the heterozygote OR was 2.144 (95% CI, 1.490–3.085; P < 0.001), the dominant OR was 2.078 (95% CI, 1.462–2.954; P < 0.001), and the overdominant OR was 0.496 (95% CI, 0.348–0.706; P < 0.001). For the 5A/6A variant of the MMP3 gene, the heterozygote OR was 0.839 (95% CI, 0.722–0.975; P = 0.022), the dominant OR was 0.846 (95% CI, 0.733–0.976; P = 0.022), and the overdominant OR was 1.141 (95% CI, 1.001–1.301; P = 0.049). For the M235T variant of the AGT gene, the heterozygote OR was 1.594 (95% CI, 1.179–2.155; P = 0.002), the dominant OR was 1.437 (95% CI, 1.077–1.918; P = 0.014), and the overdominant OR was 0.694 (95% CI, 0.555–0.869; P = 0.001). Positive results were observed in the AT1R gene A1166C polymorphism under 3 models (homozygote OR = 2.009; 95% CI, 1.433–2.816; P < 0.001; recessive OR 1.874; 95% CI, 1.353–2.595; P < 0.001; and dominant OR = 1.350; 95% CI, 1.105–1.649; P = 0.003). ImplicationsThe G298A variant of eNOS, the 5A/6A variant of MMP3, the M235T variant of AGT, and the A1166C variant of A1TR may increase the risk of restenosis after PCI.

Association of Angiotensin II Type I Receptor (AGTR1) Gene Polymorphism and Type 2 Diabetes &amp; Nephropathy among the Eastern Indian Bengali Patients

Genetic polymorphisms of the angiotensin II type I receptor (AGTR1), has been reported to be the most probable candidate genes for hypertension, diabetes and complication of diabetes. Ethnic differences in the frequencies of these gene genotypes have also been reported. As there is no data available for AGTR1 polymorphism and T2DM in the Bengali population, it’s our attempt to fill the scientific gap. To investigate whether the angiotensin II type I receptor gene A1166C (rs5186) polymorphism is associated with a risk of type 2 diabetes and nephropathy in Indian Bengali patients, in a case-control study, the AGTR1 gene (rs5186; A1166C) was examined in type 2 diabetic patients with and without nephropathy (T2DM: N=246; T2DNH: N= 168) and normal control (N=304) participants and genotyped using PCR-RFLP methods. Result of Fisher exact test for allelic association of SNP rs5186 exhibits significant difference in the allele frequencies between the control and T2DM groups (p= 0.0308). It is observed through the 4 genotypic model tests that additive model predicted significant association than basic genotype, dominant and recessive models and shows significant difference between CON vs. T2DM groups (p = 0.038). The present study reveals that the A1166C polymorphism (rs5186) of AGTR1 has a positive association with T2DM. This polymorphism with C allele may contribute to diabetic complication, nephropathy development particularly in T2DM patients.

Association between A1298C and C677T methylenetetrahydrofolate reductase gene polymorphisms and the risk of acute lymphoid and myeloid leukemia

Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism, DNA methylation and synthesis. Two MTHFR polymorphisms, C677T and A1298C, have been associated with reduced enzyme activity. Rapidly replicating cell types, such as hematopoietic cells, may be especially sensitive to changes in the availability of intracellular folate. The aim of this case-control study was to evaluate whether the mentioned polymorphisms in MTHFR gene plays a role in altering susceptibility to acute myeloid leukemia and acute lymphoblastic leukemia. Material and methods: 281 patients comprising 101 patients with acute lymphoblastic leukemia and 180 patients with acute myeloid leukemia as well as 490 normal individuals as control group were studied for the C677T and the A1298C MTHFR gene polymorphisms using PCR. The PCR products were digested with HinfI and Mbo‌‌‌‌‌II restriction enzymes respectively (RFLP). The results were electrophoresed on agaros gel and analyzed using SPSS software. Results: The number of patients with acute lymphoblastic leukemia who had C677T polymorphism was less than the control group, but this difference was not significant. Also, combination of C677T/A1298C genotypes in both case and control groups, showed no increase of susceptibility to acute myeloid leukemia and/or acute lymphoblastic leukemia risk. There was no significant relationship between common MTHFR variants and the risk of acute myeloid leukemia and acute lymphoblastic leukemia in controls and the cases. Conclusion: Our findings showed that the MTHFR C677T and A1298C gene variants do not have a major influence on the susceptibility to acute lymphoblastic leukemia and acute myeloid leukemia in Iranian individuals. However, the C677T polymorphism has a protection role in acute lymphoblastic leukemia group, but this difference was not statistically significant.

Analysis of thrombophilic gene mutations in coronary artery ectasia.

Coronary artery ectasia (CAE) is defined as localized or diffuse dilatation in the coronary artery lumen of at least 1.5 times the diameter of adjacent healthy reference segments. The etiology of CAE is still unknown, but the most likely cause is atherosclerosis. The aim of this study was to evaluate several gene polymorphisms that are thought to have an effect on the development of coronary atherosclerosis and have been shown to cause thrombophilia in CAE patients. The factor V Leiden (G1691A), factor V H1299R, prothrombin G20210A, factor XIII V34L, beta-fibrinogen-455 G>A, plasminogen activator inhibitor (PAI)-1 4G/5G, and methylenetetrahydrofolate reductase (MTHFR) C677T, and MTHFR A1298C polymorphisms were evaluated in 66 patients with CAE and 32 individuals with normal coronary arteries. Comparison of the CAE and control groups revealed that the clinical features and the frequency of polymorphism in the thrombophilic genes were similar in both groups. However, when heterozygous and/or homozygous polymorphism was compared between groups, it was found that there was a significantly higher finding of thrombophilic gene polymorphism in the CAE group (p=0.023). Thrombophilic gene polymorphism may be associated with the formation and clinical presentation of CAE.

Duboka venska tromboza i rekurentna plućna embolija kod pacijenta sa trombofiličnim mutacijama i generalizovanom psorijazom - prikaz slučaja

Abstract: Introduction: Genetic risk factors that increase venous thromboembolism risk are disorders in the synthesis or activity of coagulation factors. Factor V Leiden, prothrombin (20210-A), antithrombin deficiency, protein C and protein S deficiency, and hyperhomocysteinemia are the most common venous thromboembolism-related gene mutations. When genetic factors are combined with non-provoking risk factors (obesity, psoriasis, smoking and previous venous thromboembolism) the result is increased venous thromboembolism risk for each factor individually. Previous venous thromboembolism is one of the strongest risk factors, even in patients actively treated with anticoagulants. Patients are more likely to have recurrent venous thromboembolism with longer duration. Psoriasis is a complex immune-mediated disease, associated with cardiovascular risk, hypercoagulability markers and elevated homocysteine. Lots of observational reports suggest increased incidence of venous thromboembolic events in patient with psoriasis. Case presentation: We present patient with inherited thrombophilia and chronic diffuse plaque psoriasis complicated with deep venous thrombosis and pulmonary embolism. DNA analysis indicates the presence of homozygosis for Factor V Leiden mutation as well as heterozygosis for Factor XIII V34L, PAI-1 5G/4G and MTHFR A1298C polymorphism. Dermatological anamnesis is positive for plaque psoriasis since 12 years ago. Conclusion: The presentation of this case indicates an association between venous thromboembolism and chronic psoriasis. All patients with recurrent thromboembolism, hereditary thrombophilia, and moderate to severe psoriasis should be considered to be at higher risk for venous thromboembolism and appropriately treated.

Research Article Genotyping of A1298C polymorphism of the &lt;i&gt;MTHFR&lt;/i&gt; gene in patients with iron deficiency anemia at the Institute of Hematology and Hemotherapy of Amapá

Research Article Genotyping of A1298C polymorphism of the &lt;i&gt;MTHFR&lt;/i&gt; gene in patients with iron deficiency anemia at the Institute of Hematology and Hemotherapy of Amapá

Methylene tetrahydrofolate reductase gene mutation in sickle cell anaemia patients in Lagos, Nigeria.

IntroductionThe significant causes of mortality among individuals with sickle cell anaemia (SCA) such as acute chest syndrome and cerebrovascular disease are related to vascular occlusion. Polymorphisms of the methylene tetrahydrofolate reductase (MTHFR) gene in persons with sickle cell anaemia have been suggested as a potential risk for vaso-occlusive events, with the C677T and A1298C polymorphisms being the commonest. This study therefore aimed to establish the pattern of MTHFR C677T and A1298C gene mutations among adults with HbSS phenotype attending the Haematology Clinic in Lagos State University Teaching Hospital Lagos, Nigeria.MethodsA cross-sectional study was done among SCA patients attending the Haematology Clinic of the Lagos State University Teaching Hospital (LASUTH), using age and sex matched HbAA controls. DNA extraction and gene analysis were done. The selective amplification of a particular segment of the DNA by polymerase chain reaction (PCR) was done and subsequent digestion of the amplified MTHFR gene into its various fragments.ResultsThe overall prevalence of the C677T mutation among participants was 19.3% (37 of 192), while the prevalence of A1298C was 15% (29 of 192).ConclusionThe prevalence of MTHFR C677T was higher than A1298C mutations among sickle cell anaemia subjects.

The Genetic Profile of Thrombophilia in Reproductive Disorders

Some cases of reproductive disorders have a thrombotic etiology. Considering the importance of establishing the cause of miscarriage, we investigated the incidence and associated risks of the most common thrombophilic genes polymorphism - FV G1691A, FV H1299A, Prothrombin G20210A, PAI-1, Factor XIII V34L, MTHFR C677T, MTHFR A1298C and EPCR genes, in women with reproductive disorders. In our research we included 139 women with reproductive disorders and risk for hereditary trombophilia and 139 healthy females without any personal or family history of vein thrombosis or recurrent pregnancy loss. For detection of thrombophilic genes polymorphism we used CVD StripAssay�(ViennaLab, Austria) and the tests� protocols were followed as described by the manufacturer. Our results showed that the concomitant presence of MTHFR A1298C and Factor XIII V34L gene polymorphism had a significant association for recurrent pregnancy loss, while FV H1299A (R2) and MTHFR A1298C gene polymorphisms were correlated with subfertility. We therefore consider that these patients should be recognized as high risk for poor pregnancy outcomes and monitored with specialized follow-up.

The Genetic Profile of Thrombophilia in Reproductive Disorders

Some cases of reproductive disorders have a thrombotic etiology. Considering the importance of establishing the cause of miscarriage, we investigated the incidence and associated risks of the most common thrombophilic genes polymorphism - FV G1691A, FV H1299A, Prothrombin G20210A, PAI-1, Factor XIII V34L, MTHFR C677T, MTHFR A1298C and EPCR genes, in women with reproductive disorders. In our research we included 139 women with reproductive disorders and risk for hereditary trombophilia and 139 healthy females without any personal or family history of vein thrombosis or recurrent pregnancy loss. For detection of thrombophilic genes polymorphism we used CVD StripAssay�(ViennaLab, Austria) and the tests� protocols were followed as described by the manufacturer. Our results showed that the concomitant presence of MTHFR A1298C and Factor XIII V34L gene polymorphism had a significant association for recurrent pregnancy loss, while FV H1299A (R2) and MTHFR A1298C gene polymorphisms were correlated with subfertility. We therefore consider that these patients should be recognized as high risk for poor pregnancy outcomes and monitored with specialized follow-up.