Association study between idiopathic male infertility and the MTHFD1 G1958A SNP

Couple infertility is a global health problem and according to the World Health Organization approximately one couple in seven is affected by fertility or subfertility problems. Male infertility in humans has been acknowledged as the cause of couple’s inability to have children in 20-50% of total cases and although there have been much progress in understanding its etiology many of the case are still considered to be idiopathic, arising from an unknown cause. The MTHFD1 G1958A SNP (single nucleotide polymorphism) by altering the structure of the encoded enzyme, a trifunctional enzyme which catalyzes the interconversion of 1-carbon derivatives of tetrahydrofolate could lead to an abnormal folate status, hyperhomocysteinemia and altered DNA synthesis. The folate metabolic pathway is essential for DNA methylation, DNA synthesis, as well as methylation of various other substrates, thus a disruption to this cellular pathway may lead to major pathologic consequences. By means of molecular genetic techniques, respectively PCR-RFLP (Polymerase Chain Reaction - Restriction Fragment Length Polymorphism) we investigated the possible role of MTHFD1 G1958A SNP in the etiology of male infertility by comparing the distribution of this SNP in two groups: a group of 66 men with idiopathic azoospermia or severe oligozoospermia and a control group of 67 healthy men which have at least one child. Statistical analysis was performed by means of chi-square and Fisher’s exact tests. The genotype distribution in the two groups was in agreement with the Hardy-Weinberg Law. We obtained the following genotype stratification: 18 (27.3%) G/G, 27 (40.9%) G/A, 21(31.8%) A/A in the cases group compared to 19(28.4%) G/G, 36(53.7%) G/A, 12(17.9%) A/A in the control group; with a p value of 0.23 (odds ratio: 1.85, Cl 95%: 0.71-4.82) when comparing the mutant homozygous status (A/A) to the normal homozygous status (G/G). Because of the profound social, familial, medical and emotional outcomes that male infertility generates a greater emphasis should be made in understanding its etiology. After performing the first study on a Romanian population, due to the similar distribution of the studied polymorphism in the two groups we can state the MTHFD1 G1958A SNP is not a risk factor for idiopathic male infertility in our study group

Genetic determination of irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. According to the Rome III criteria, IBS is defined as recurrent abdominal pain or discomfort for at least 3 d per month during the previous 3 mo associated with two or more of the following symptoms: improvement with defecation, onset associated with a change in the frequency of stool and/or onset associated with a change in form or appearance of stool. There is growing evidence regarding the genetic contribution in IBS, however the precise etiology of IBS is still unknown. The evaluation of the genetic influence is based on twin studies, familial aggregation and genetic epidemiological investigations. Most studies showed a concordance for IBS significantly greater in monozygotic than in dizygotic twins. The majority of the studies have shown that familial aggregation may represent exposures to a similar environment, as well as the influence of genetic factors. Whereas no specific gene has been identified in association with IBS, recent studies have noticed the importance of polymorphisms in the promoter region of the serotonin reuptake transporter gene, G-protein beta 3 subunit gene (C825T), cholecystokinin receptor (CCKAR gene 779T>C), and high-producer tumor necrosis factor genotype. Further studies are necessary to determine how genetic factors influence the clinical manifestations and therapeutical response in IBS patients

Genotype-phenotype correlations in patients treated with acenocoumarol / Corelaţii genotip-fenotip la pacienţii trataţi cu acenocumarol

Scop: Această cercetare are drept scop stabilirea unei corelaţii genotip-fenotip la pacienţii trataţi cu acenocumarol şi studierea factoriilor genetici (polimorfismele VKORC1 şi CYP2C9), care ar putea influenţa valorile INR în timpul iniţierii terapiei anticoagulante orale cu acenocumarol. Material şi metode: Am inclus 131 de pacienţi care necesitau tratament cu acenocumarol, 70 (53,4%) femei şi 61 (46,6%) bărbaţi, internaţi în Clinica Medicala 5 din Cluj-Napoca, între 2009-2011. Am studiat influenţa vârstei, sexului, medicaţiei concomitente şi a genelor CYP2C9 şi VKORC1 asupra valorii INR măsurate în ziua a treia de tratament şi asupra diferenţei dintre această valoare şi valoarea INR măsurată la debutul tratamentului (INRDIF). Rezultate şi concluzii: Am demonstrat o diferenţă semnificativă statistic pentru INR3 şi valorile INRDIF la pacienţii cu genotip AA şi cei cu genotip GG ai polimorfismului c.- 1639G>A al genei VKORC1. Prezenţa genotipului AA al polimorfismului c.- 1639G>A al genei VKORC1 a determinat o creştere de 15,7 ori a riscului ca un pacient să prezinte INR supraterapeutic după 2 zile de tratament cu 4 mg de acenocumarol

FGB -455 G>A and GP IIIa PIA1/A2 polymorphisms in a group of Romanian stroke patients

Introduction: Being a multifactorial disease, stroke is one of a major causes of death and disability worldwide. Several genetic polymorphisms have been associated with stroke etiophatology and FGB −455 G>A and GP IIIa PIA1/A2 are among them. In the present study, we investigated the association between FGB −455 G>A and GP IIIa PIA1A2 polymorphisms and the risk of ischemic stroke in a group of Romanian stroke patients

Cystathionine β-synthase 844ins68 Genetic Polymorphism in Spontaneous Abortion Susceptibility

Aim: Genetic polymorphisms in homocysteine-related genes are subject of a large body of research in pregnancy and newborn associated pathologies. The enzyme cystationine β-synthase (CBS) is involved in the transsulfuration pathway of homocysteine to cysteine. Our objective was to analyze the association of a common polymorphism exhibited by the CBS gene, 844ins68, with idiopathic spontaneous abortions (SA). Material and Methods: 131 patients with a history of at least one unexplained SA and 135 healthy women with at least one successful pregnancy and no SA were included in a case-control study. Simplex PCR was used to genotype the cases and control volunteers for the CBS 844ins68 polymorphism. Fisher’s exact test was performed to obtain the odds-based parameters describing the relationship between the two variables. Results: The variant allele was encountered with a frequency of 0.08 in the SA group and 0.048 in controls. The dominant model analysis of risk revealed the OR 1.957, 95%CI [0.920, 4.162], Fisher’s p = 0.09. Conclusion: The findings suggest possible effects of this polymorphism in SA risk that did not reach the significance level in this study. Future studies might validate or clarify the association between CBS 844ins68 and idiopathic SA

Interindividual Variability of Apixaban Plasma Concentrations: Influence of Clinical and Genetic Factors in a Real-Life Cohort of Atrial Fibrillation Patients

(1) Background: Prescribing apixaban for stroke prevention has significantly increased in patients with non-valvular atrial fibrillation (NVAF). The ABCB1 genotype can influence apixaban absorption and bioavailability. The aim of the present study was to assess the factors that influence apixaban’s plasma level and to establish if a certain relationship has clinical relevance. (2) Methods: Fifty-three NVAF patients were treated with 5 mg apixaban twice/day (70.0 years, range: 65–77, 60.4% men). Trough and peak plasma concentrations of apixaban were determined by liquid chromatography-tandem mass-spectrometry (LC-MS/MS), and ABCB1 genotyping was performed. (3) Results: Apixaban plasma concentrations varied considerably. They were higher in women than in men (311.2 ng/dL vs. 252.2 ng/dL; p = 0.05) and were lower in patients with heart failure (149.4 ng/dL vs. 304.5 ng/dL; p < 0.01). Creatinine clearance was inversely correlated with the apixaban plasma level (Spearman correlation: r = −0.365; p = 0.007 for trough concentrations). No statistically significant differences between the genotypic groups of ABCB1 rs1045642 and ABCB1 rs4148738 were found in the trough or peak apixaban plasma concentrations. (4) Conclusions: Pharmacokinetic parameters are influenced by several clinical factors of which renal function is the major determinant. Plasma concentrations measured in women had higher values than those measured in men, and heart failure was associated with decreased plasma levels of apixaban

Thrombophilia genetic testing in Romanian young women with acute thrombotic events: role of Factor V Leiden, Prothrombin G20210A, MTHFR C677T and A1298C polymorphisms / Evaluarea genetică a trombofiliilor la femei tinere din România cu evenimente acute trombotice: rolul Factorului V Leiden, Protrombinei G20210A, polimorfismelor MTHFR C677T și A1298C

Objective: The present case-control study aimed at evaluating the contribution of thrombophilic polymorphisms to acute venous (VTE) as well as arterial thrombotic events (ATE) in a population of young women with few traditional thrombotic factors (CVRF)

COVID-19 Impact on Chronic Myeloid Leukemia Patients

(1) Background: Chronic myeloid leukemia (CML) is a blood dyscrasia that accounts for about 20% of all leukemia cases. Tyrosine kinase inhibitors (TKIs) are used as first line treatment of CML. The 2019 SARS-CoV-2 outbreak raised new concerns for CML patients, such as whether CML increases the risk of contracting COVID-19, whether TKIs increase that risk, whether these drugs are safe to use during the infection, and whether any other hematologic parameters influence infection outcomes. (2) Methods: In our study we addressed these intriguing questions by using a retrospective analysis of 51 CML patients treated at the Ion Chiricuta Cancer Center, Cluj-Napoca, Romania. Furthermore, we investigated the effects of currently approved COVID-19 vaccines in our CML patients treated with tyrosine kinase inhibitors. (3) Results: Our results have shown that hemoglobin level upon diagnosis of CML has been the only hematologic parameter correlated to the risk of contracting COVID-19 in our CML patients. (4) Conclusions: TKI treatment did not negatively influence COVID-19 risk or the response to the vaccine in our patients. The safety profile of the currently approved COVID-19 vaccines was similar to that of the general population

CYP4F2 and VKORC1 Polymorphisms Amplify the Risk of Carotid Plaque Formation

Introduction: Atherosclerosis represents the process by which fibrous plaques are formed in the arterial wall, increasing its rigidity with a subsequent decrease in blood flow which can lead to several cardiovascular events. Seeing as vitamin K antagonists are involved in the pathogenesis of atherosclerosis, we decided to investigate whether polymorphisms in genes that influence vitamin K metabolism might have an impact in modulating the risk of plaque formation. Patients and Methods: In the current study we included adult patients admitted in the Clinical Municipal Hospital of Cluj-Napoca without any carotid or femoral plaques clinically visible at the initial investigation, and a five year follow-up was subsequently performed. We recorded the following patient characteristics: age at inclusion, gender, area of living, smoking, presence of carotid and/or femoral plaques at five years, ischemic heart disease, arterial hypertension, atrial fibrillation, heart failure, diabetes mellitus, obesity, dyslipidemia, drug (oral anticoagulants, antihypertensives, hypolipidemic, anti-diabetic) use and status for the following gene polymorphisms: VKORC1 1639 G>A, CYP4F2 1347 G>T and GGCX 12970 C>G. Results: We observed that the major predictor of both carotid and femoral plaque formation is represented by ischemic cardiac disease. VKORC1 and CYP4F2 polymorphisms did not predict plaque formation, except for VKORC1 homozygous mutants. Nonetheless, both VKORC1 and CYP4F2 interacted with ischemic cardiac disease, increasing the risk of developing a carotid plaque, while only CYP4F2, but not VKORC1, interacted with ischemic cardiac disease to increase the risk of femoral plaque formation. Conclusions: We documented that CYP4F2 and VKORC1 polymorphisms boost the proinflammatory plaque environment (observed indirectly through the presence of ischemic heart disease), increasing the risk of plaque development