Circulating Homocysteine Levels Research Articles

The Impact of the Dietary Intake of Vitamin B12, Folic Acid, and Vitamin D3 on Homocysteine Levels and the Health-Related Quality of Life of Levodopa-Treated Patients with Parkinson's Disease-A Pilot Study in Romania.

Previous studies have shown that the levodopa treatment of Parkinson's disease (PD) elevates circulating homocysteine levels, which are associated with an increased risk of cardiovascular and neurological disorders, or thrombosis. The present trial aimed to examine whether the intake of vitamin B12, folic acid, and vitamin D3 supplements improved homocysteine level and quality of life (QoL). An interventional prospective trial was conducted in multiple centers across Romania. Participants with clinically established PD taking at least 300 mg/day of levodopa for more than 1 year received a daily tablet of a supplement containing 800 UI of vitamin D3, 1000 µg of folic acid, and 15 µg of vitamin B12. They were followed for 6 months and their serum homocysteine, vitamin B12, vitamin D, and QoL scores were measured at baseline and at 6 months of treatment. QoL was measured using a 15D questionnaire, which assesses mobility, vision, hearing, breathing, sleeping, eating, speech, excretion, usual activities, mental function, discomfort and symptoms, depression, distress, vitality, and sexual activity. Twenty-four PD patients with a mean age of 71 ± 5.04 years (54.2% male and 45.8% female) finished the study. After the intervention, the mean score of speech, mental function, discomfort and symptoms, depression, and QoL significantly increased (p < 0.05 for all). Also, the serum homocysteine and vitamin D were significantly enhanced (p < 0.0001 and p = 0.025, respectively). Changes in vitamin B12 were not statistically significant at 6 months of treatment (p = 0.996). No gender differences were found among the changes that we have demonstrated for homocysteine, vitamin B12, vitamin D, and QoL levels (p < 0.05 for all). The findings of this study showed that the dietary intake of vitamin B12, folic acid, and vitamin D3 remarkably decreased the dimensions of homocysteine and finally increased the total score of QoL in PD patients. We have successfully captured the potential benefits of the supplementation regimen over time and provided insights into the broader implications for managing PD with a focus on nutritional support.

Homocysteine, vitamin B12, and folate circulating levels in women with and without polycystic ovary syndrome: A systematic review and meta-analysis.

Some studies have reported that homocysteine, vitamin B12, and folic acid levels are associated with polycystic ovary syndrome (PCOS), whereas other studies yielded controversial results. This study aimed to systematize the available evidence of homocysteine, vitamin B12, and folate levels in women with and without PCOS. Systematic review and meta-analysis. A systematic search without language restrictions was performed on PubMed, Ovid/Medline, Scopus, Embase, and Web of Science. In addition, the reference lists of the selected studies were reviewed. The Newcastle-Ottawa Scale was employed to evaluate the quality of studies. The means and standard deviations of the outcomes were pooled as standardized mean differences (SMDs) with 95% confidence intervals (CI). Furthermore, the DerSimonian and Laird method was employed for the quantitative synthesis. A total of 75 studies met the eligibility criteria for at least one outcome. Patients with PCOS had higher circulating homocysteine levels than those without (SMD: 0.82; 95% CI: 0.62-1.02, n = 70 studies, p < 0.001). This trend remained in the sensitivity and subgroup analyses by world regions of studies, assay methods, and insulin resistance. No significant differences were observed in circulating vitamin B12 (SMD: -0.11; 95% CI: -0.25 to 0.03; n = 17 studies, p = 0.13) and folate levels (SMD: -0.2; 95% CI: -0.68 to 0.27; n = 17 studies, p = 0.41) between patients with and without PCOS. (i) Patients with PCOS exhibited significantly higher homocysteine levels than those without, and (ii) no significant differences were observed in both vitamin B12 and folate levels in women with and without PCOS. PROSPERO ID (CRD42023432883).

The effect of diet-induced weight loss on circulating homocysteine levels in people with obesity and type 2 diabetes

Background/aimsHaving type 2 diabetes (T2D) in combination with being overweight results in an additional increase in cardiovascular disease (CVD) risk. In addition, T2D and obesity are associated with increased levels of total homocysteine (tHcy), possibly contributing to the CVD risk. Weight loss dieting has positive effects on several CVD risk factors, but whether it affects tHcy remains unclear. Therefore, the aim of this study was to determine the effect of a calorie restricted diet on tHcy in overweight people with T2D.MethodsIn this post-hoc analysis of the POWER study, adults with T2D and a BMI greater than 27 kg/m² were included from the outpatient diabetes clinic of the Erasmus Medical Center, Rotterdam. The patients were subjected to a very low-calorie diet with fortified meal replacements for 20 weeks. Before and after this intervention, blood samples were collected to measure tHcy and other CVD risk factors like glycaemic and lipid parameters.Results161 overweight participants with T2D were included, with a mean age of 54 years (range 26–74), mean weight of 104.6 ± 19.9 kg and mean HbA1c of 62.7 ± 14.3 mmol/mol. At baseline, men displayed higher tHcy than women, and tHcy level was positively correlated with body weight and triglyceride levels, while it was negatively correlated with renal function and HDL cholesterol. During the intervention, bodyweight was reduced by a mean of 9.7% (from 104.6 ± 19.9 to 94.5 ± 18.1 kg p < 0.001), and all measured glycaemic and lipid blood parameters improved significantly. However, tHcy remained unchanged (from 12.1 ± 4.1 to 12.1 ± 4.2 umol/L, p = 0.880). The change in tHcy during the intervention was negatively associated with the change in weight and BMI (p = 0.01 and p = 0.008, respectively). People who lost < 10 kg (n = 92) had a mean tHcy change of -0.47 umol/L, while people who lost more than ≥ 10 kg (n = 69) had a mean tHcy change of 0.60 umol/L (p = 0.021).ConclusionIn conclusion, our data show that a calorie restricted diet does not affect tHcy in people with T2D and obesity, despite the use of meal replacements fortified with folic acid and vitamin B12. Our data showed a negative correlation between change in tHcy levels and weight loss, suggesting that people who lost more weight (> 10 kg) showed an increase in tHcy. Future studies should explore the potential increase in tHcy induced by weight loss dieting and target the question if tHcy reduction strategies during weight loss could be clinically beneficial.

No causal effect of genetically determined circulating homocysteine levels on psoriasis in the European population: evidence from a Mendelian randomization study.

Although numerous studies demonstrated a link between plasma homocysteine (Hcy) levels and psoriasis, there still exists a certain level of controversy. Therefore, we conducted a Mendelian randomization study to investigate whether homocysteine plays a causative role in the development or exacerbation of psoriasis. A two-sample Mendelian randomization (MR) analysis was conducted. Summary-level data for psoriasis were acquired from the latest R9 release results from the FinnGen consortium (9,267 cases and 364,071 controls). Single nucleotide polymorphisms (SNPs) robustly linked with plasma Hcy levels at the genome-wide significance threshold (p < 5 × 10-8) (18 SNPs) were recognized from the genome-wide meta-analysis on total Hcy concentrations (n = 44,147 participants) in individuals of European ancestry. MR analyses were performed utilizing the random-effect inverse variance-weighted (IVW), weighted median, and MR-Egger regression methods to estimate the associations between the ultimately filtrated SNPs and psoriasis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. MR analyses revealed no causal effects of plasma Hcy levels on psoriasis [IVW: odds ratio (OR) = 0.995 (0.863-1.146), p = 0.941; weighed median method: OR = 0.985 (0.834-1.164), p = 0.862; MR-Egger regression method: OR = 0.959 (0.704-1.305), p = 0.795]. The sensitivity analyses displayed no evidence of heterogeneity and directional pleiotropy, and the causal estimates of Hcy levels were not influenced by any individual SNP. Our study findings did not demonstrate a causal effect of genetically determined circulating Hcy levels on psoriasis.

Modulation of blood pressure regulatory genes in the Agtrap-Plod1 locus associated with a deletion in Clcn6.

The AGTRAP‐PLOD1 locus is a conserved gene cluster containing several blood pressure regulatory genes, including CLCN6, MTHFR, NPPA, and NPPB. Previous work revealed that knockout of Clcn6 on the Dahl Salt‐Sensitive (SS) rat background (SS‐Clcn6) resulted in lower diastolic blood pressure compared to SS‐WT rats. Additionally, a recent study found sickle cell anemia patients with mutations in CLCN6 had improved survival and reduced stroke risk. We investigated whether loss of Clcn6 would delay the mortality of Dahl SS rats on an 8% NaCl (HS) diet. No significant difference in survival was found. The ability of Clcn6 to affect mRNA expression of nearby Mthfr, Nppa, and Nppb genes was also tested. On normal salt (0.4% NaCl, NS) diets, renal Mthfr mRNA and protein expression were significantly increased in the SS‐Clcn6 rats. MTHFR reduces homocysteine to methionine, but no differences in circulating homocysteine levels were detected. Nppa mRNA levels in cardiac tissue from SS‐Clcn6 rat in both normotensive and hypertensive conditions were significantly reduced compared to SS‐WT. Nppb mRNA expression in SS‐Clcn6 rats on a NS diet was also substantially decreased. Heightened Mthfr expression would be predicted to be protective; however, diminished Nppa and Nppb expression could be deleterious and by preventing or blunting vasodilation, natriuresis, and diuresis that ought to normally occur to offset blood pressure increases. The conserved nature of this genetic locus in humans and rats suggests more studies are warranted to understand how mutations in and around these genes may be influencing the expression of their neighbors.

Plasma homocysteine levels and handgrip strength in postmenopausal women

Objective This study evaluated handgrip strength (HGS), circulating homocysteine levels and related factors in postmenopausal women. Methods This study is a sub-analysis of a prospective cohort of 303 postmenopausal women aged 62.7 ± 6.9 years who had HGS measures with a digital dynamometer as the primary outcome, and plasma homocysteine and creatinine levels and glomerular filtration rate (GFR) measures as the secondary outcomes. Results The average HGS was 22.5 ± 4.0 kg, 29.4% of women had dynapenia (HGS < 20 kg), adiposity was 40.3 ± 5.4% and 9.57% of women had hyperhomocysteinemia (homocysteine >15 μmol/l). There were no differences between tertiles of homocysteine and HGS (p = 0.641). Plasma homocysteine levels were unrelated to HGS (r = −0.06) and correlated with age (r = 0.17), GFR (r = −0.28) and creatinine (r = 0.23). Hyperhomocysteinemia was not associated with HGS (odds ratio [OR] = 0.98 [95% confidence interval (CI): 0.89; 1.08]) or dynapenia (OR = 1.10 [95% CI: 0.45; 2.47]). The risk of presenting low HGS were not significantly associated with homocysteine (OR = −0.08 [95% CI: −0.21; 0.06]) and were associated with age (OR = −0.23 [95% CI: −0.29; −0.17]), adiposity (OR = −6.52 [95% CI: −9.53; −3.50]) and creatinine (OR = 6.22 [95% CI: 2.48; 9.97]). Conclusions HGS and dynapenia were unrelated to hyperhomocysteinemia. Age, GFR and creatinine were significantly associated with plasma homocysteine levels.

Investigating the causality of metabolites involved in one-carbon metabolism with the risk and age at onset of Parkinson's disease: A two-sample mendelian randomization study

With the aging population and increasing life expectancy, Parkinson's disease (PD), a neurological disorder rapidly increasing in morbidity and mortality, is causing a huge burden on society and the economy. Several studies have suggested that one-carbon metabolites, including homocysteine, vitamin B6, vitamin B12 and folate acid, are associated with PD risk. However, the results remain inconsistent and controversial. Thus, we performed a two-sample Mendelian randomization (MR) study to detect the causality between one-carbon metabolites and PD susceptibility as well as age at PD onset. We collected several genetic variants as instrumental variables from large genome-wide association studies of one-carbon metabolites (homocysteine: N = 14, vitamin B6: N = 1, vitamin B12: N = 10, folate acid: N = 2). We then conducted MR analyses using the inverse variance-weighted (IVW) approach and additional MR-Egger regression, weighted median and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods to further test causality. The results showed no causal association between circulating homocysteine levels and PD risk (p = 0.868) or age at PD onset (p = 0.222) with the IVW method. Meanwhile, similar results were obtained by three complementary analyses. In addition, we did not observe any evidence that the circulating levels of vitamin B6, vitamin B12 and folate acid affected the risk of PD or age at onset of PD. Our findings implied that lowering homocysteine levels through vitamin B6, vitamin B12 or folate acid supplementation may not be clinically helpful in preventing PD or delaying the age at PD onset.

Association of homocysteine with ankylosing spondylitis: a systematic review and meta-analysis

BackgroundHyperhomocysteinemia is associated with autoimmune diseases such as ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Current findings regarding plasma/serum homocysteine (HCY) levels in AS patients are inconsistent. This study aims to systematically evaluate the association between circulating HCY levels and AS.MethodsOnline electronic databases (PubMed, Web of Science, Embase, ScienceDirect, China National Knowledge Infrastructure (CNKI), and Wanfang data) were used to retrieve all relevant articles published up to May 7, 2020. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated using the random-effect model, Stata16 software.ResultsNine articles containing 778 AS patients and 522 controls were included in this meta-analysis. No significant differences in HCY levels were found between AS and control groups (pooled SMD = 0.46, 95% CI = − 0.30 to 1.23, P = 0.23). However, subgroup analysis suggested that HCY levels were significantly higher (P < 0.05) in the AS group treated with methotrexate (MTX) compared with the control group. In contrast, HCY levels were significantly (P < 0.05) lower in the AS group receiving anti-TNF-α treatment compared with the control group. No significant differences were detected between HCY levels and disease activity scores (Bath AS disease activity index, BASDAI), and methylenetetrahydrofolate reductase (MTHFR) C677T genotype.ConclusionThis meta-analysis indicates that HCY levels are similar between AS and controls, and do not correlate with disease activity. However, different medical treatments cause fluctuations of circulating HCY levels in AS patients. Further and larger-scale studies are needed to confirm these findings.Trial registrationThis study was registered at international prospective register of systematic reviews (PROSPERO), registration number: CRD42020184426.

Assessing the long-term stability of total bilirubin protected from light under refrigerated conditions

Previous studies have shown conflicting results regarding circulating homocysteine levels in patients with type 2 diabetes.This observational study included 2121 patients with angiographically proven coronary artery disease (507 patients with type 2 diabetes and 1614 patients without diabetes). Circulating homocysteine levels, methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, renal function, presence of coronary artery disease (CAD) diagnosed by coronary angiography, and circulating folate and vitamin B12 status were assessed. Plasma homocysteine levels [median (25th; 75th percentile)] were significantly higher in patients with diabetes than in those without [12.4 μmol/L (9.9 μmol/L; 15.9 μmol/L) versus 11.7 μmol/L (9.6 μmol/L; 14.5 μmol/L), P = 0.011]. Diabetes affected homocysteine levels only in patients with a glomerular filtration rate <90 mL/min [13.0 μmol/L (10.5 μmol/L; 16.7 μmol/L) in patients with diabetes versus 12.2 μmol/L (10.1 μmol/L; 15.2 μmol/L) in patients without diabetes, P = 0.006] but not in those with a glomerular filtration rate ≥90 mL/min [10.1 μmol/L (8.1 μmol/L; 12.4 μmol/L) versus 10.2 μmol/L (8.8 μmol/L; 12.3 μmol/L), P = 0.267]. Multivariable analysis did not show an independent association between diabetes and homocysteine level (P = 0.342).Circulating homocysteine levels are increased in patients with type 2 diabetes compared with non-diabetic patients due to a more diabetes-associated adverse risk profile rather than to diabetes itself.

Genome-Wide Meta-Analysis of Homocysteine and Methionine Metabolism Identifies Five One Carbon Metabolism Loci and a Novel Association of ALDH1L1 with Ischemic Stroke

Circulating homocysteine levels (tHcy), a product of the folate one carbon metabolism pathway (FOCM) through the demethylation of methionine, are heritable and are associated with an increased risk of common diseases such as stroke, cardiovascular disease (CVD), cancer and dementia. The FOCM is the sole source of de novo methyl group synthesis, impacting many biological and epigenetic pathways. However, the genetic determinants of elevated tHcy (hyperhomocysteinemia), dysregulation of methionine metabolism and the underlying biological processes remain unclear. We conducted independent genome-wide association studies and a meta-analysis of methionine metabolism, characterized by post-methionine load test tHcy, in 2,710 participants from the Framingham Heart Study (FHS) and 2,100 participants from the Vitamin Intervention for Stroke Prevention (VISP) clinical trial, and then examined the association of the identified loci with incident stroke in FHS. Five genes in the FOCM pathway (GNMT [p = 1.60×10−63], CBS [p = 3.15×10−26], CPS1 [p = 9.10×10−13], ALDH1L1 [p = 7.3×10−13] and PSPH [p = 1.17×10−16]) were strongly associated with the difference between pre- and post-methionine load test tHcy levels (ΔPOST). Of these, one variant in the ALDH1L1 locus, rs2364368, was associated with incident ischemic stroke. Promoter analyses reveal genetic and epigenetic differences that may explain a direct effect on GNMT transcription and a downstream affect on methionine metabolism. Additionally, a genetic-score consisting of the five significant loci explains 13% of the variance of ΔPOST in FHS and 6% of the variance in VISP. Association between variants in FOCM genes with ΔPOST suggest novel mechanisms that lead to differences in methionine metabolism, and possibly the epigenome, impacting disease risk. These data emphasize the importance of a concerted effort to understand regulators of one carbon metabolism as potential therapeutic targets.

Activation of transsulfuration pathway by salvianolic acid a treatment: a homocysteine-lowering approach with beneficial effects on redox homeostasis in high-fat diet-induced hyperlipidemic rats

BackgroundElevated homocysteine is a cardiovascular risk factor in hyperlipidemia. Transsulfuration pathway provides an endogenous pathway for homocysteine conversion to antioxidant glutathione (GSH). Salvianolic acid A (Sal A) contains two molecules of caffeic acid and one molecule of danshensu that is capable of enhancing homocysteine transsulfuration, which led to the hypothesis that Sal A has activatory effect on transsulfuration pathway and this effect may have beneficial effects on both homocysteine and redox status in hyperlipidemia.Methods and resultsTo test this hypothesis, we developed a rat model of hyperlipidemia induced by high-fat diet for 16 weeks, during which rats were treated with 1 mg/kg salvianolic acid A (Sal A) for the final 4 weeks. Activities of key enzymes and metabolite profiling in the transsulfuration pathway revealed that hyperlipidemia led to elevated plasma homocysteine levels after 16-week dietary treatment, which was associated with reduced activities of homocysteine transsulfuration enzymes, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). The impaired transsulfuration pathway prevented homocysteine transsulfuration to cysteine, resulting in cysteine deficiency and subsequent reduction in GSH pool size. The redox status was altered in the setting of hyperlipidemia as indicated by GSH/GSSG ratio. Sal A treatment increased hepatic CBS and CSE activities, which was associated with reduced accumulation in circulating homocysteine levels and attenuated decline in hepatic cysteine content in hyperlipidemic rats. Sal A also led to an increase in GSH pool size, which subsequently caused a restored GSH/GSSG ratio. The activatory effect of Sal A on CBS was also observed in normal rats and in in vitro experiment.ConclusionOur results suggest that activation of transsulfuration pathway by Sal A is a promising homocysteine-lowering approach that has beneficial effects on redox homeostasis in hyperlipidemic settings.

Hypercyst(e)inemia in CDO−/− mouse model is associated with an accumulation of tissue acid-labile sulfide and low circulating homocysteine levels

Hypercyst(e)inemia in CDO−/− mouse model is associated with an accumulation of tissue acid-labile sulfide and low circulating homocysteine levels

Early reduction of circulating homocysteine levels in Goto–Kakizaki rat, a spontaneous nonobese model of type 2 diabetes

Diabetes mellitus is associated with increased risk for cardiovascular disorders, which are major causes of mortality in this disease. Hyperhomocysteinemia, defined by high plasma homocysteine levels, is an independent risk factor for the development of cardiovascular diseases. Type 2 diabetic patients have higher circulating homocysteine levels than healthy subjects and these levels are even higher in plasma of obese than nonobese diabetic patients. Homocysteine metabolism that has been studied in 2 animal models of type 2 diabetes with obesity led to conflicting data. The aim of the present study was to analyze homocysteine metabolism in a spontaneous nonobese model of type 2 diabetes, the Goto–Kakizaki rats at various successive and well characterized stages of the disease: during early postnatal normoglycemia, at the onset of hyperglycemia (around weaning), and during chronic mild hyperglycemia with progressive insulin resistance. Compared to age-matched Wistar controls, Goto–Kakizaki rats showed lower plasma levels of homocysteine and a falling trend in its major byproduct antioxidant, glutathione, from the prediabetic stage onwards. Concomitantly, Goto–Kakizaki rats exhibited increased liver activity of cystathionine beta synthase, which catalyzes the condensation of homocysteine with serine in the first step of the transsulfuration pathway. These results emphasize a strong association between homocysteine metabolism and insulin via the first step of the hepatic transsulfuration pathway in Goto–Kakizaki rats.

Associations between plasma homocysteine levels, aortic stiffness and wave reflection in patients with arterial hypertension, isolated office hypertension and normotensive controls.

The aim of this study was to evaluate any possible association of homocysteine with arterial stiffness indices in patients with essential arterial hypertension (AH), isolated office hypertension (IOH) and normotensive controls. The final cohort comprised 231 normotensives (NTs, 119 males), 480 patients with IOH (196 males) and 1188 patients with essential AH (713 males). All patients were screened for plasma homocysteine levels and lipidaemic profile and underwent aortic compliance and wave reflection assessment by using carotid-femoral pulse wave velocity (PWVc-f) and aortic augmentation index corrected for heart rate (AIx) accordingly. In the total population, stepwise multiple linear regression analysis showed that homocysteine levels remained a significant determinant of PWV (beta (SE): 0.056 (0.007), P<0.001) and AIx (beta (SE): 0.236 (0.052), P<0.001) independently of the traditional factors affecting arterial stiffness and wave reflection. When the three groups were examined separately, homocysteine levels remained an independent determinant of PWFc-f in all groups (NT: beta (SE): 0.070 (0.022), P=0.002; IOH: beta (SE): 0.109 (0.015), P<0.001; AH: beta (SE): 0.040 (0.009), P<0.001). However, homocysteine levels remained an independent determinant of AIx only in the IOH and AH, but not in the NT group (IOH: beta (SE): 0.302 (0.124), P=0.015; AH: beta (SE): 0.183 (0.057), P=0.001; NT: beta (SE): 0.308 (0.240), P=0.200). This study points to an independent relationship between circulating homocysteine levels, aortic compliance and wave reflection.

Homocysteine, folic acid, and the prevention of vascular disease.

Reduction of circulating homocysteine levels by folic acid suggests an additional approach to the prophylaxis of certain forms of vascular disease related to atherogenic amino acids.

Buerger`s Disease and Hyperhomocysteinemia: Is there a Relationship?

Thromboangiitis obliterans, also known as Buerger's disease, is a cause of juvenile lower limb ischaemia. Buerger's disease is idiopathic and one of diagnostic criteria is the absence of atherosclerotic risk factors other than smok- ing. A possible involvement of thrombophilia has been investigated and the role of hyperhomocysteinemia is still matter of discussion. We describe 9 patients with Buerger's disease followed-up for the past 3 years. We found a significant in- crease in circulating homocysteine levels (mean: 31.6 in patients vs 8.2 μmol/L in control subjects). We also analyzed the C677T mutation of MTHFR; 5/9 Buerger's patients were heterozygotes and 4/9 homozygotes for the mutation as com- pared with 3 heterozygotes in the control group. Our data, although preliminary, suggest a possible role of homocysteine in the pathogenesis of Buerger's disease as one of the causes of endothelial dysfunction. The role of MTHFR C677T vari- ant must be further evaluated in larger trials involving patients with Buerger's disease.

Methylenetetrahydrofolate reductase (MTHFR) C677T genetic polymorphism and late infarct-related coronary artery patency after thrombolysis

In patients with acute myocardial infarction (AMI), a persistently occluded infarct-related artery (IRA) is associated with unfavorable prognosis and genetic factors may be contributing factors to thrombolysis failure. One-hundred and one consecutive patients treated with intravenous thrombolysis during AMI were blind-tested for methylenetetrahydrofolate reductase (MTHFR) and circulating homocysteine levels and underwent protocol angiography 14 +/- 6 days after the event. IRA was patent in 61 patients and occluded in 40. Overall MTHFR 677TT frequency was 22%. Patients with MTHFR 677TT homozygosis had higher prevalence of occluded IRA (73%) versus those with MTHFR 677CT/CC genotype (30%, P < 0.001); MTHFR 677TT genotype predicted independently the risk of IRA occlusion with a specificity of 90% (odds ratio 3.8, 95% confidence interval 1.1-9.1; P = 0.03). Moreover, patients with occluded IRA and MTHFR 677TT genotype had the highest homocysteine levels (21 +/- 7.6 micromol/l vs. < or =14.9 +/- 3.8 micromol/l; P = 0.011). In patients with AMI, MTHFR 677TT homozygosis is independently associated with a persistently occluded IRA after thrombolysis. This finding may have pathophysiological and therapeutic implications for recanalization strategies in patients with AMI.

Errata

Basic & Clinical Pharmacology & ToxicologyVolume 102, Issue 5 p. 489-489 Free Access Errata This article corrects the following: Assessing Intrauterine Influences on Offspring Health Outcomes: Can Epidemiological Studies Yield Robust Findings? George Davey Smith, Volume 102Issue 2Basic & Clinical Pharmacology & Toxicology pages: 245-256 First Published online: January 22, 2008 First published: 13 October 2009 https://doi.org/10.1111/j.1742-7843.2007.246_2.xAboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat In [1], second author Christian Wiegand was not originally included in the author list when the article was published Online Early on 28 November 2007. This was corrected on 17 March 2008 and re-published online with a note to detail the change. In [2], page 251 – column 1, paragraph 2, line 17 - should read “(a genetic variant that is associated with methyltetrahydrofolate reductase activity and circulating homocysteine levels; TT genotype being associated with higher homocysteine levels)”. Page 252, column 1, paragraph 2, lines 5-6 – should read “For example, in one study mental development at age 7.5 was delayed among offspring of mothers lacking a genetic variant associated with more rapid alcohol metabolism.” In [3], the positions of I/R and SKF-38393 were mistakenly reversed in Figure 3(B). The correct Figure 3(B) is as follows: We apologise for these errors. References 1 Kampkötter A, Wiegand C, Timpel C, Röhrdanz E, Chovolou Y, Kahl R et al. Increased expression of catalase in human hepatoma cells by the soy isoflavone, daidzein. Basic Clin Pharmacol Toxicol 2008; 102: 437– 42. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 2 Davey Smith G. Assessing intrauterine influences on offspring health outcomes: can epidemiological findings yield robust results? Basic Clin Pharmacol Toxicol 2008; 102: 245– 56. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 3 Li H-Z, Han L-P, Jiang C-M, Li H, Zhao Y-J, Gao J et al. Effect of dopamine receptor-1 on apoptosis of cultured neonatal rat cardiomyocytes in simulated ischaemia/reperfusion. Basic Clin Pharmacol Toxicol 2008; 102: 329– 36. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar Volume102, Issue5May 2008Pages 489-489 ReferencesRelatedInformation

Circulating homocysteine levels in patients with radiofrequency catheter ablation for atrial fibrillation

This study investigated the potential association between homocysteine levels and cardiovascular events or atrial fibrillation (AF) recurrence following radiofrequency catheter ablation (RFCA) in patients with AF. Blood samples were obtained prior to the RFCA procedure. Levels of homocysteine and carboxy-terminal telopeptide of collagen type I (CITP), a collagen type I degradation marker, were measured in 96 patients receiving RFCA; 62 paroxysmal or persistent AF patients and 34 paroxysmal supra-ventricular tachycardia patients. Patients were followed up for 2.1 +/- 1.5 years. Plasma homocysteine levels were significantly higher in patients with persistent AF (P < 0.05) compared with levels in paroxysmal AF and control patients. Homocysteine levels also positively correlated with left atrial dimension (LAD) (P < 0.01) and CITP levels (P < 0.001). While no significant correlation was found between basal homocysteine levels and recurrent AF after RFCA in AF patients, patients in the high homocysteine group exhibited a significantly higher rate of cardiovascular events without AF recurrence compared with those in the low homocysteine group (P < 0.05). High homocysteine levels are associated with the presence of persistent AF, which is accompanied by increased CITP levels and LAD. Also confirmed is the role of homocysteine as a risk factor for the pathogenesis of cardiovascular events after RFCA in AF patients. Measurement of homocysteine level may provide useful information for the managing cardiovascular risk in patients with AF.

Methyl group metabolism in maternal and fetal hepatic tissues is altered by diabetes and retinoic acid treatment

Adequate methyl group supply is vital for numerous biological reactions, especially during development. A lack of methyl groups, B‐vitamins, and changes in relevant enzymes, can result in a host of pathologies, including neural tube defects. If inappropriately activated, hepatic glycine N‐methyltransferase (GNMT) a regulatory enzyme in folate and methyl group metabolism, leads to methyl deficiency. We have shown that both a diabetic state and retinoic acid (RA) treatment result in activation of GNMT. The goal of this pilot study was to determine if induction of GNMT during pregnancy alters methyl group metabolism in the fetus. Non‐diabetic and diabetic (STZ) pregnant rats treated with and without RA, were sacrificed on d 18 of gestation for collection of blood and liver tissue. Two hepatic immunoreactive proteins were clearly detected (32 and ~36 kD) in liver tissue. The lighter form (L‐GNMT) was more responsive in maternal liver, whereas the heavier protein (H‐GNMT) dominated in fetal liver. Rats receiving both RA and STZ exhibited elevated maternal hepatic GNMT activity, L‐GNMT abundance, and DNA hypomethylation, and reduced circulating homocysteine levels. Fetal liver expressed only H‐GNMT which was slightly responsive to treatment; however, L‐GNMT expression was evident in the combined treatment group. Fetal hepatic tissue did not exhibit changes in DNA methylation, due to the lack of L‐GNMT expression.