Increased Homocysteine Levels Research Articles

The methylenetetrahydrofolate reductase genotype 677CT and non-alcoholic fatty liver disease have a synergistic effect on the increasing homocysteine levels in subjects from Chongqing, China

The methylenetetrahydrofolate reductase (MTHFR) genotypes 677CT and 677TT are associated with elevated serum homocysteine (Hcy) levels by means of lowering the activity of MTHFR, and the increase in serum Hcy may be linked to increased susceptibility to non-alcoholic fatty liver disease (NAFLD). However, there are contradictory reports of the relationship among the MTHFR 677CT gene polymorphism, Hcy, and NAFLD. Therefore, the aim of this study was to identify potential associations and interactions of either Hcy levels or the MTHFR 677CT gene polymorphism with the susceptibility to NAFLD in a Chinese population. The association between the MTHFR 677 CT gene polymorphism and Hcy levels was determined in 243 subjects with NAFLD and 388 healthy subjects without NAFLD using polymerase chain reaction-restriction fragment length polymorphism analysis and high-performance liquid chromatography. In subjects with NAFLD, there was no statistical difference in the genotypic and allelic frequencies of the MTHFR 677 CT gene polymorphism, while serum Hcy levels were significantly higher in subjects with NAFLD. Furthermore, these results strongly suggest that the MTHFR 677CT gene polymorphism and NAFLD have a potential synergistic effect on Hcy elevation, although the MTHFR 677CT gene polymorphism was not correlated with NAFLD in a Chinese population.

Betaine reduces \u03b2-amyloid-induced paralysis through activation of cystathionine-\u03b2-synthase in an Alzheimer model of Caenorhabditis elegans

BackgroundThe neurodegenerative disorder Alzheimer’s disease is caused by the accumulation of toxic aggregates of β-amyloid in the human brain. On the one hand, hyperhomocysteinemia has been shown to be a risk factor for cognitive decline in Alzheimer’s disease. On the other hand, betaine has been demonstrated to attenuate Alzheimer-like pathological changes induced by homocysteine. It is reasonable to conclude that this is due to triggering the remethylation pathway mediated by betaine-homocysteine-methyltransferase. In the present study, we used the transgenic Caenorhabditis elegans strain CL2006, to test whether betaine is able to reduce β-amyloid-induced paralysis in C. elegans. This model expresses human β-amyloid 1–42 under control of a muscle-specific promoter that leads to progressive, age-dependent paralysis in the nematodes.ResultsBetaine at a concentration of 100 μM was able to reduce homocysteine levels in the presence and absence of 1 mM homocysteine. Simultaneously, betaine both reduced normal paralysis rates in the absence of homocysteine and increased paralysis rates triggered by addition of homocysteine. Knockdown of cystathionine-β-synthase using RNA interference both increased homocysteine levels and paralysis. Additionally, it prevented the reducing effects of betaine on homocysteine levels and paralysis.ConclusionOur studies show that betaine is able to reduce homocysteine levels and β-amyloid-induced toxicity in a C. elegans model for Alzheimer’s disease. This effect is independent of the remethylation pathway but requires the transsulfuration pathway mediated by cystathionine-β-synthase.

T44. A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF THE EFFECTS OF VITAMIN B12, B6 AND FOLIC ACID ON COGNITION AND SYMPTOMS IN FIRST-EPISODE PSYCHOSIS: THE VITAMINS IN PSYCHOSIS STUDY

BackgroundVitamin B12, vitamin B6 and folic acid are homocysteine-reducing agents. People with schizophrenia have been found to have increased homocysteine levels. Elevated homocysteine has been associated with impaired cognition. Previous research in chronic schizophrenia has shown that supplementation with folate plus vitamin B12 can improve cognition and clinical symptoms. Whether homocysteine lowering agents are effective in first-episode psychosis is unknown. The aim of this study was to investigate if adjunctive vitamin B12, B6 and folic acid can lower homocysteine and improve symptomatology and cognition in people with first-episode psychosis.MethodsThis was a randomised, double-blind, placebo-controlled trial conducted at the Early Psychosis Prevention and Intervention Centre (EPPIC) in Melbourne, Australia. One hundred and twenty patients aged 15–26 years with first-episode psychosis consented and were randomised to receive folic acid 5mg, vitamin B12 0.4mg, and vitamin B6 50mg or placebo, each taken once-daily for 12 weeks as an adjunct to antipsychotic medication. Co-primary measures were change in cognition as measured by a composite score from a battery of 11 tests and total symptomatology (PANSS) over 12 weeks. Secondary outcomes included additional cognitive, symptom, functioning, tolerability and safety measures.ResultsOf the 120 participants randomised in the study, 20 dropped out with no follow-up assessments and were excluded from analysis. Of the remaining 100 participants, 52 were in the vitamins group and 48 the placebo group. At baseline, the two treatment groups had lower levels of folate and vitamin B12 intake than healthy controls, but did not differ from each other. Vitamin B12, B6 and folic acid reduced homocysteine levels in the vitamin group over 12 weeks. The homocysteine lowering effects of the vitamins did not confer a major advantage over placebo therapy in improving the co-primary PANSS (p=.75) or composite cognition (p=0.79) outcomes over 12 weeks. There was a significant difference between groups among females in the cognitive domain of speed of processing (p=.049) and attention/vigilance (p=0.002), in which the mean performance of the placebo group declined over 12 weeks, whereas performance in the vitamin group remained showed improvement.DiscussionFolic acid, B12 and B6 supplementation appears well tolerated and safe in first-episode psychosis and lowers homocysteine levels in this population. However, supplementation may not offer extra benefits to all patients with first-episode psychosis, with the possible exception of speed of processing and attention/vigilance. Although previous research suggests that males preferentially benefit, our findings suggest that there may be a specific beneficial effect on cognition for females with first-episode psychosis.

Association between hyperhomocysteinemia and metabolic syndrome with early carotid artery atherosclerosis: A cross-sectional study in middle-aged Chinese population.

Homocysteine is a modifiable, independent risk factor for cardiovascular disease. The association between hyperhomocysteinemia and metabolic syndrome with the presence of early carotid artery atherosclerosis remains unknown in middle-aged Chinese adults. Chinese adults (n = 1607) of Han ethnicity, age 35 to 65 y, and living in their communities >2 y were surveyed. Hyperhomocysteinemia was defined as homocysteine concentrations >15 µmol/L. Carotid intima-media thickness and carotid plaque were examined by ultrasonography. All participants were classified into four groups by hyperhomocysteinemia and metabolic syndrome status. Participants with both hyperhomocysteinemia and metabolic syndrome had the highest levels of waist circumference and systolic blood pressure compared with the three other groups. The highest proportion of increased carotid intima-media thickness (61.3%) was in the subgroup of both hyperhomocysteinemia and metabolic syndrome. After adjustments for the covariates, the risk of increased carotid intima-media thickness was only significantly higher in the group with metabolic syndrome but without hyperhomocysteinemia (odds ratio: 1.47; 95% confidence interval, 1.13-1.93) compared with people without hyperhomocysteinemia and metabolic syndrome. Furthermore, statistically significant variances of prevalence of plaque among the four subgroups were not discovered. Our study demonstrated that metabolic syndrome had a strong effect on carotid intima-media thickness However, the increased homocysteine levels were not significantly associated with early carotid artery atherosclerosis in middle-aged Chinese people.

Evaluation of Vitamin B12 status in type 2 Diabetes Mellitus Patients on Metformin therapy

Background: B12 deficiency is a silent epidemic with serious consequences. Long term use of metformin has been associated with malabsorption of vitamin B12 leading to its deficiency along with increased homocysteine levels. With this background we designed this study to assess the status of vitamin B12 and its markers in type 2 diabetes mellitus patients on metformin therapy who are attending tertiary care hospital in the peripheral area of Pondicherry.Aims and Objective: The current study aims to study the relationship if any, between the glycemic status and the status of Vitamin B12 among T2DM patients on metformin therapy.Materials and Methods: A case control study was done with a sample size of 100 (50 case and 50 control). The patients were selected according to the inclusion criteria and their blood sample were analyzed for the various parameters. The markers of vitamin B12 status are studied among both the control and the patients with T2DM on metformin therapy and compared with their glycaemic status.Results: There is a significant increase in the levels of FBS, HbA1c, insulin and C-peptide in the study group. It was observed that the mean levels of homocysteine and Methylmalonic acid were significantly higher with lower levels of vitamin B12 in patients who were on metformin therapy.Conclusion: There is moderate correlation between the markers of B12 status and levels of fasting blood sugar as well as HbA1C. There is a significant correlation between insulin and C-peptide with the markers of vitamin B12 status.Asian Journal of Medical Sciences Vol.9(2) 2018 9-12

Poorly Controlled Homocystinuria: A Rare Cause of Ischemic Priapism?

We report on the 1st case of ischemic priapism secondary to poorly controlled homocystinuria. Homocystinuria is a rare, autosomal recessive, inherited disorder of metabolism that is caused by a deficiency of cystathionine synthase, leading to marked hyperhomocysteinemia. Arterial and/or venous thromboemboli are a major cause of mortality and morbidity in patients with homocystinuria. Untreated patients have a 50% chance of having a vascular event by 30 years of age. Increased homocysteine levels have been reported to upregulate prothrombotic factors and downregulate antithrombotic factors; in particular, increased homocystinuria has been found to downregulate nitric oxide (NO). Mice that are deficient in NO synthase in the cavernosal smooth muscles have a higher incidence of priapism. Decrease in NO synthase causes downregulation of cyclic guanosine monophosphate, phosphodiesterase type 5A, and Rho A/Rho-kinase. Because persistently increased homocysteine also downregulates NO, a similar mechanism could be proposed for priapism secondary to homocystinuria. In patients presenting with priapism, specific features of homocystinuria should be sought; in selected patients, screening with plasma total homocysteine might be appropriate. Ischemic priapism secondary to homocystinuria appears to respond well to the standard treatment options of aspiration, intracavernosal injection with phenylephrine, and, if required, a shunting procedure.Johnson M, Murphy E, Raheem A, Ralph D. Poorly Controlled Homocystinuria: A Rare Cause of Ischemic Priapism? Sex Med 2018;6:171–173.

Is the 1298A>C polymorphism in the MTHFR gene a risk factor for arterial ischaemic stroke in children? The results of meta-analysis

An elevated level of homocysteine is a risk factor for vascular diseases, brain atrophy and several other disorders. The 1298A>C polymorphism (rs1801131) leads to mildly decreased MTHFR activity. Previously, it was observed that the MTHFR 1298A>C polymorphism in combined analysis with the MTHFR 677C>T polymorphism increases homocysteine levels. However, conflicting results on its relation to ischaemic stroke in children can be found. We conducted a meta-analysis to analyse possible connections between the MTHFR 1298A>C polymorphism and ischaemic stroke in paediatric patients. We identified available data published before December 2016 using appropriate keywords and searching PubMed as well as the references cited in the found articles. Eight case–control studies were included in the meta-analysis (426 children with stroke and 778 controls). Statistical analyses were made using R and Comprehensive Meta-Analysis softwares to investigate the impact of polymorphism in four models: dominant, recessive, additive and allelic. No publication bias was observed in the meta-analysis. We demonstrated no relationship between the 1298A>C polymorphism and ischaemic stroke in children in the case of recessive, additive and allelic models. However, the results of the dominant model analysis should be treated with caution due to the sensitivity analysis results. After omitting one of the included study, we observed a significant association between the carriers of the MTHFR C allele (cases with AC + CC genotypes) and ischaemic stroke in children (OR 1.35 95% CI 1.02–1.79, p = 0.035 in a fixed effects model). In conclusion, the 1298A>C polymorphism in the MTHFR gene is not a risk factor for ischaemic stroke in paediatric patients.

Effects of training versus short exercise session on homocysteine levels in women with different body mass

PurposeHomocysteine is a non-protein amino acid and elevated blood levels are often caused by inappropriate lifestyles, leading to atherosclerosis and cardiovascular diseases. The aim of this study was to determine the levels of homocysteine after a 9-month training program.MethodsThe group studied consisted of obese and overweight women, as well as women with normal body mass. During the training program, control examinations were carried out four times and the following parameters were analyzed: homocysteine blood levels, body mass, BMI, a single 10-minute exercise at a workload of 100W and the VO2max measured using the Astrand–Ryhming method.ResultsThe highest homocysteine levels were found in obese women and the lowest in lean women. Higher levels were observed in older women (aged over 50 years) compared to younger women (aged below 50 years). The differences were clearly visible in obese women. Homocysteine levels decreased after the 9-month training program. A single exercise performed every three months during the training program resulted in an increase in homocysteine levels or no changes.ConclusionsHigher homocysteine levels in the blood after a single exercise are likely caused by faster metabolism of this amino acid. Exercise of moderate intensity leads to a decrease in homocysteine levels in the blood, especially in obese women. Regular physical activity should therefore be recommended not only to prevent and treat obesity but, most importantly, atherosclerosis.

Correlation between homocysteine levels and stroke in patients with acute ischemic stroke

Ischemic strokes are mostly caused by atherosclerosis, and increased homocysteine levels are considered to play a role in atherosclerosis. The aim of this study was to investigate serum total homocysteine (tHcy) levels in the first 24 h of ischemic stroke patients and to analyze the correlation between tHcy levels and the clinical severity of ischemic stroke. The study included a total of 151 participants including a patient group of 83 patients diagnosed with acute ischemic stroke and a control group of 68 age- and gender-matched subjects with no history of ischemic vascular diseases between June 2006 and December 2007. Demographic characteristics of were recorded for each participant and stroke severity was assessed using the modified Rankin Scale (mRS) in each patient. Serum tHcy, vitamin B12, folic acid, and fibrinogen levels as well as platelet count and lipid profiles were measured for each participant. Serum tHcy levels were significantly higher and the folic acid levels were significantly lower in the patient group compared to the control group (p

A genetic perspective of Metformin induced Vitamin B12 deficiency in Type 2 Diabetes mellitus patients

Metformin, a commonly prescribed hypoglycemic agent is a first line medication for the management of Type 2 diabetes mellitus. Numerous studies have depicted that metformin therapy has been associated with vitamin B12 and folate deficiency. Vitamin B12 deficiency is frequently missed or misdiagnosed by the clinicians because it is not routinely tested by most of the physicians, further the low end of the laboratory reference range is too low and misinterpreted as diabetic peripheral neuropathy. Vitamin B12 deficiency is a silent epidemic with serious consequences. Long term use of metformin has been associated with increased homocysteine levels and malabsorption of vitamin B12 leading to its deficiency and neurological manifestations. Polymorphisms of certain genes associated with the metabolism of vitamin B12 and folate might help in predicting the deficiency status of vitamin B12.Asian Journal of Medical Sciences Vol.9(1) 2018 11-14

Study of plasma homocysteine level in patients with bronchial asthma and its relation to asthma severity

Background Homocysteine (HCY) may play a role in activation of immune system in some chronic diseases, like asthma and chronic obstructive pulmonary disease. Aim The aim was to study the plasma HCY values in patients with bronchial asthma and its correlation to asthma severity. Patients and methods A total of 80 patients were enrolled, and their ages ranged from 20 to 40 years. The study populations were categorized into three groups: high reversibility asthma (n=30), low reversibility asthma (n=30), and healthy nonasthmatics (Controls n=20). For all patients, full history taking, clinical examination, chest radiography, routine laboratory investigations, pulmonary function tests, and the HCY and immunoglobulin E levels were estimated. Results The HCY measurements were found to be 8.7±0.6 µmol/l in the control group, 5.5±0.2 µmol/l in patients with high reversibility asthma, and 6.1±0.8 µmol/l in patients with low reversibility asthma. So, there was a significant variance between studied groups regarding HCY levels, but both high and low reversibility groups had low HCY when compared with control group. Moreover, the high reversibility asthma had low HCY levels when compared with low reversibility groups but without significant difference. Conclusion Plasma HCY levels, instead of being increased, may be in the low normal range or decreased in patients with asthma, most probably owing to hypoxia and in the absence of factors leading to increased HCY levels.

Toxicity of the readily leachable fraction of urban PM2.5 to human lung epithelial cells: Role of soluble metals

Fine airborne particulate matter (PM2.5) has been repeatedly associated with adverse health effects in humans. The PM2.5 soluble fraction, and soluble metals in particular, are thought to cause lung damage. Literature data, however, are not consistent and the role of leachable metals is still under debate. In this study, Winter and Summer urban PM2.5 aqueous extracts, obtained by using a bio-compatible solution and different contact times at 37 °C, were used to investigate cytotoxic effects of PM2.5 in cultured lung epithelial cells (A549) and the role played by the leachable metals Cu, Fe, Zn, Ni, Pb and Cd. Cell viability and migration, as well as intracellular glutathione, extracellular cysteine, cysteinylglycine and homocysteine concentrations, were evaluated in cells challenged with both PM2.5 extracts before and after ultrafiltration and artificial metal ion solutions mimicking the metal composition of the genuine extracts. The thiol oxidative potential was also evaluated by an abiotic test. Results demonstrate that PM2.5 bioactive components were released within minutes of PM2.5 interaction with the leaching solution. Among these are i) low MW (<3 kDa) solutes inducing oxidative stress and ii) high MW and/or water-insoluble compounds largely contributing to thiol oxidation and to increased homocysteine levels in the cell medium. Cu and/or Ni ions likely contributed to the effects of Summer PM2.5 extracts. Nonetheless, the strong bio-reactivity of Winter PM2.5 extracts could not be explained by the presence of the studied metals. A possible role for PM2.5 water-extractable organic components is discussed.

The Effects of Methionine-Enriched and Vitamins (Folate, Pyridoxine and Cobalamine)-Deficient Diet on Exploratory Activity in Rats - A Brief Report

Abstract The aim of this study was to evaluate the impact of increased homocysteine levels induced by methionine nutritional overload (twice as standard) and deficiency of the vitamins folate, pyridoxine and cobalamine, which plays an important role in homocysteine metabolism in anxiety-related behaviour, expressed by means of exploratory activity in rats. Twenty-three male Wistar albino rats (4 weeks old, 100±15 g body weight) were divided into three groups: control (n=8), methionine-enriched (Meth+, 7.7 g of methionine/kg chow, n=7) and methionine-enriched vitamin-deficient (Meth+Vit-, 7.7 g of methionine/ kg chow, deficient in folate, pyridoxine and cobalamine - 0.08, 0.01 and 0.01 mg/kg, n=8). All animals had free access to food and water for 30 days. Behavioural testing was performed using the elevated plus maze (EPM) test. Standard parameters for vertical exploratory activity, the number of rearings and the number of head-dippings, as well as the total exploratory activity (summarizing overall exploratory activity in the EPM) were significantly reduced following 30 days of methionine nutritional overload (p&lt;0.05, p&lt;0.05 and p&lt;0.01, respectively). A methionine-enriched diet coupled with a reduction in some B vitamins resulted in a more pronounced decline in exploratory drive observed in the EPM test compared to the control (p&lt;0.01). The decline in total exploratory activity associated with vitamin deficiency was significant compared to the Meth+ group (p&lt;0.05). The results of this study highlight the important role of homocysteine in the modulation of exploratory activity in rats. Decreased exploratory drive induced by both a methionine-enriched and vitamin-deficient diet could be attributed to an anxiogenic effect of hyperhomocysteinemia.

Methylene Tetrahydrofolate Reductase Deficiency: the Hidden Risk in Paediatric Anaesthesia.

Methylene tetrahydrofolate reductase (MTHFR) deficiency is an autosomal recessive disorder that results in increased homocysteine levels in the body. Hyperhomocysteinemia causes a predisposition to venous and arterial thrombosis and ischaemic insults. The incidence of the deficiency is around 40% in some countries. In this study, we aimed to evaluate the effects of anaesthetic agents in children with MTHFR deficiency. Twelve paediatric patients with an MTHFR enzyme deficiency who underwent surgery in a ten-month period in a single centre were retrospectively evaluated. Demographic data, homocysteine levels before and after surgery, anaesthesia management and postoperative complications were recorded. In four patients, propofol was used both for anaesthesia induction and total intravenous anaesthesia (TIVA). Eight patients received sevoflurane for both induction and maintenance of anaesthesia. Nitrous oxide (N2O) was not used in any patients. There was not a significant difference between the preoperative and postoperative homocysteine levels (p>0.05). Twenty-four hours after the surgery, the homocysteine levels were within normal limits. No complications were observed. Sevoflurane and propofol have no deleterious effects on homocysteine levels in patients with MTHFR deficiency. Avoidance of N2O is the key point for anaesthetic consideration regarding these patients.

Moderate hyperhomocysteinemia induced by short-term dietary methionine overload alters bone microarchitecture and collagen features during growth

AimsIn general, hyperhomocysteinemia is increasingly appreciated as a risk factor for various diseases, including osteoporosis. However, its effects in non-adults remain largely unknown. Our aim was to determine whether dietary-caused increased homocysteine levels have deleterious effects on bone structure during growth. Main methodsWe developed a model of moderate hyperhomocysteinemia caused by short-term methionine nutritional overload in growing rats. 30-days-old male Wistar albino rats were randomly assigned to either experimental group subject to a 30-days hypermethionine diet or control group. High-resolution 3D assessment of bone geometry and microarchitecture, as well as fluorescence spectroscopic analysis of bone matrix were performed. Key findingsShort-term moderate hyperhomocysteinemia (~30μmol/L) achieved in the study notably affected bone and cartilage characteristics. Parameters of the cortical bone geometry in the experimental group indicated peculiar reorganization of the bone cross-section. Trabecular bone microarchitecture was especially sensitive to hyperhomocysteinemia showing clearly negative bone balance in the experimental group (almost 30% reduced bone volume, mainly due to ~25% decrease in trabecular number as well as markedly reduced trabecular connections). Fluorescent spectroscopy of bone matrix revealed multiple alterations to collagen spectra due to homocysteine accumulation in bone, indicative of broken collagenous cross-links. SignificanceGiven that appropriate accrual of bone mass during growth has important effects on the risk of osteoporosis in adulthood, understanding the skeletal effects of dietary-induced hyperhomocysteinemia in non-adults is essential for interpreting its importance as a modifiable risk factor for osteoporosis and improving programs to preserve/re-establish bone health.

Sodium Arsenite-Induced Learning and Memory Impairment Is Associated with Endoplasmic Reticulum Stress-Mediated Apoptosis in Rat Hippocampus.

Chronic arsenic exposure has been associated to cognitive deficits. However, mechanisms remain unknown. The present study investigated the neurotoxic effects of sodium arsenite in drinking water over different dosages and time periods. Based on results from the Morris water maze (MWM) and morphological analysis, an exposure to sodium arsenite could induce neuronal damage in the hippocampus, reduce learning ability, and accelerate memory impairment. Sodium arsenite significantly increased homocysteine levels in serum and brain. Moreover, sodium arsenite triggered unfolded protein response (UPR), leading to the phosphorylation of RNA-regulated protein kinase-like ER kinase (PERK) and eukaryotic translation initiation factor 2 subunit α (eIF2α), and the induction of activating transcription factor 4 (ATF4). Arsenite exposure also stimulated the expression of the endoplasmic reticulum (ER) stress markers, glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and the cleavage of caspase-12. Furthermore, exposure to arsenite enhanced apoptosis as demonstrated by expression of caspase-3 and TUNEL assay in the hippocampus. The results suggest that exposure to arsenite can significantly decrease learning ability and accelerate memory impairment. Potential mechanisms are related to enhancement of homocysteine and ER stress-induced apoptosis in the hippocampus.

Associations between serum homocysteine levels and anxiety and depression among children and adolescents in Taiwan

Although evidence suggests that homocysteine levels are elevated in severe mental illness in children, findings regarding homocysteine levels in youth with anxiety and depression are scarce. Therefore, this study examined the association of homocysteine levels with anxiety and depression in a community sample of students aged 6–13 years. In total, 649 students were selected from the first, fourth, and seventh grades of schools in Taipei, Taiwan, in 2010. These students completed a hospital-based health examination, which included physical examination, blood sample collection, and questionnaire administration. The data were analysed through multiple linear regression. Among the seventh-grade boys, both depression (adjusted β = 0.044, 95% confidence interval (CI) = 0.004–0.084) and anxiety (adjusted β = 0.052, 95% CI = 0.013–0.091) were independently associated with increased homocysteine levels. In further dichotomisation, compared with students with low anxiety levels, those with moderate to high anxiety levels were significantly positively associated with elevated serum homocysteine levels (adjusted β = 0.091, 95% CI = 0.003–0.180). Our results suggest that increased depression and anxiety may be positively associated with higher serum homocysteine levels in older boys. Our results provide essential data on the biological aspects underlying anxiety and depression in the studied population.

The role of molecular genetic alterations in genes involved in folate and homocysteine metabolism in multifactorial diseases pathogenesis

The molecular genetic modifications in multiple genes involved in folate and homocysteine metabolism play the pivotal role in the development of hyperhomocysteinemia. Hyperhomocysteinemia is observed in 5% of patients worldwide and accompanies various multifactorial diseases, including neurodegenerative, autoimmune and vascular disorders and tumors. It should be noted that increased homocysteine level itself may point to some imbalance in the organism and represent a diagnostic marker of the development of some pathology. The present review describes the role of molecular-genetic modifications in one carbon metabolism accompanying different multifactorial diseases, including congenital birth defects, vascular disorders, diabetes, and hormone-dependent cancers such as breast and ovarian cancer. Data of the association between the SNPs in functionally significant genes involved in the one carbon metabolism and pathologies mentioned above were demonstrated. In addition, we firstly represent the data of the involvement of epigenetic factors (hypermethylation and miRNA) in regulation of these genes in multifactorial diseases. The section devoted to the role of molecular-genetic impairments in the genes involved in homocysteine metabolism associated with breast and ovarian cancer includes worldwide findings and our own results.

Effect of short-term administration of methionine on the ovary and uterus in a rat

Methionine is necessary for development but overuse of it can not only cause growth retardation but also damage organs such as the liver and cardiovascular system. The purpose of this research was to determine the effect of short-term administration of methionine on the ovaries and uterus in a rat. Forty adult female rats were randomly allocated into four equal groups: each received 50, 100 or 200 mg/kg BW l-methionine in 0.5 mL normal saline or just 0.5 mL normal saline (control) intraperitoneally for 20 days. On day 21, all rats were euthanized and tissues were taken for histological evaluation. Also, plasma homocysteine (Hcy) level was assessed in all groups. No difference was observed between the ovaries in all treatment and control groups; however, in methionine-injected groups, some histopathological changes were observed in the uterus such as atrophy in endometrial glands and the presence of inflammatory cells in the endo- and myometrium. Histopathological findings showed uterine infiltration of inflammatory cells in the methionine-injected groups which increased with increasing injected methionine levels. Also, all treatment groups showed increasing homocysteine levels compared to controls. These results show short-term administration of methionine and its associated homocysteinaemia has no effect on the ovary and its follicular structure.

Stężenie homocysteiny w surowicy krwi i styl życia katolików zamieszkujących teren Polski Południowej

Introduction: Public health specialists and nurses are interested in identifying the elements of lifestyle that prevent disease in specific human populations, including religious groups. Aim: The term lifestyle Catholic compound with the level of homocysteine in blood serum, as a risk factor for cardiovascular disease (CVD). Material and Methods: The cross-sectional study was conducted among 134 Catholics. Use of a questionnaire of own authorship, the International Physical Activity Questionnaire, Inventory Behavioral Health (HBI), Scale Experienced Stress PSS-10, laboratory tests (homocysteine), Test Fagerstrom Nicotine Dependence. Results: In more than half of Catholics diagnosed increased homocysteine levels. Knowledge of about halves of the respondents on CVD was fully satisfactory. Selected elements of life style Catholics, like physical activity, addictions, perceived stress, health behaviors in the HBI, psychosocial factors and diet deviate from the recommendations relevant to the prevention of CVD and were not significantly linked to the performance level of homocysteine in the blood serum, with the exception of a significant relationship between its proper level and the consumption of milk, whole wheat flakes, pasta and wheat groats and also not smoking cigarettes. Conclusions: Public health professionals and nurses should develop culturally specific educational interventions, taking into the life style and homocysteine levelaccount cardiovascular risk factors among followers of different religions.