Fasting Plasma Total Homocysteine Research Articles

The L-Arginine pathway may act as a mediator in the association between impaired one- carbon metabolism and hypertension.

Elevated fasting plasma total homocysteine (tHcy) and the methylenetetrahydrofolate reductase C677T polymorphism (rs1801133) have been associated with hypertension. Whether the L-Arginine pathway is involved, is unclear. We aimed to investigate whether the association between tHcy, the rs1801133 polymorphism and hypertension involves the L-Arginine pathway. THcy, plasma folate and cobalamin, erythrocyte glutathionine reductase activation coefficient, rs1801133 genotype, plasma L-Arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) were determined in a cross-sectional study of 788 adults (aged 18 to 75), randomly selected from 2 town population registers. Participants participated in a medical checkup and provided a fasting blood sample. Associations between tHcy, rs1801133 genotype and L-Arginine pathway metabolites were assessed by multiple linear regression analysis and whether the tHcy and rs1801133 genotype are associated with hypertension via the L-Arginine pathway was investigated using mediation analysis. tHcy was positively associated with ADMA (B=0.003; SE=0.001; P<0.001) and SDMA (B=0.007; SE=0.002; P<0.001) and negatively associated with the L-Arginine/ADMA (B=-1.140; SE=0.451; P<0.05) and ADMA/SDMA (B=-0.006; SE=0.003; P<0.05) ratios. The MTHFR 677 CT vs CC genotype was negatively associated with ADMA (B=-0.013; SE=0.007; P<0.05) and with SDMA (B=-0.029; SE=0.013; P<0.05) in participants under 50 years. Each standard deviation increase (37.6) in the L-Arginine/ADMA ratio was associated with reduced hypertension risk (OR [95%CI], 0.6 [0.5, 0.8]). Mediation analysis showed that tHcy and ADMA were mediators in the association between the rs1801133 TT vs CC genotypes and hypertension. Our results support the L-Arginine pathway as a mediator in the association of impaired One-Carbon metabolism and hypertension.

Pregnancy homocysteine and cobalamin status predict childhood metabolic health in the offspring.

Inadequate pregnancy cobalamin status has been associated with adverse offspring metabolic health in Indian and Nepalese studies. Studies of pregnancy cobalamin status and mid-childhood health outside of Asia are scarce. Associations between pregnancy fasting plasma total homocysteine (tHcy), cobalamin status (plasma cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA)) and mid-childhood metabolic score (MetSco) ((including fat mass index (zFMI), homeostatic model assessment of insulin resistance (zHOMA-IR) and dyslipidemia (zTG - zHDLc)/2) z-scores)) were investigated in a prospective study of 293 mother-child dyads. Highest versus low-mid pregnancy tHcy tertile was associated with higher mid-childhood MetSco, specifically with higher child zFMI. Stratifying by sex, the maternal tHcy-child MetSco association was limited to boys and confirmed for zFMI and zHOMA-IR. The maternal tHcy-child zFMI association was not mediated by birth weight z-score. First trimester plasma cobalamin was not associated with child outcomes, but other indicators of cobalamin status were. Lowest versus mid-high plasma holoTC tertile was associated with MetSco (specifically zFMI and zHOMA-IR) and highest versus low-mid plasma MMA tertile with higher MetSco and dyslipidemia in boys. Moderately elevated pregnancy tHcy and low cobalamin status were associated with mid-childhood metabolic score in boys. The pregnancy tHcy-child zFMI association was not mediated by birth weight. Fasting plasma total homocysteine (tHcy) during pregnancy and low cobalamin status during early pregnancy are associated with mid-childhood metabolic score and its components in the offspring. These findings were only significant in male offspring. The study provides new evidence that impaired one carbon metabolism during pregnancy is associated with negative health outcomes in the offspring, in a population with low prevalence of cobalamin deficiency. The maternal-offspring associations were observed in the functional markers of cobalamin status (holotranscobalamin and methylmalonic acid) and tHcy, not with plasma cobalamin concentration. Screening for low pregnancy cobalamin status should be considered.

Association of Hyperhomocysteinemia with Early Onset Atherosclerotic Peripheral Arterial Occlusive Diseases

Background: Homocysteine is increasingly recognized as an independent risk factor for vascular disease specially peripheral arterial occlusive diseases. In the present study, an attempt was made to find out the association between the raised fasting plasma total homocysteine level and early onset atherosclerotic peripheral arterial occlusive diseases (PAOD).&#x0D; Methods: In this prospective observational study a total of 50 study subjects were included. All patients were clinically and angiographically documented for atherosclerotic PAOD. All patients underwent surgical intervention as well as estimation of serum total homocysteine level. Arterial segment was sent for histopathological examination to find out whether atherosclerosis was present or not. Patients were divided into two groups- Group-1 included patients of 20-40 years of age and group-II included those of 41-60 years of age. The groups were compared to see association between elevated level of plasma homocysteine and atherosclerotic peripheral arterial occlusive diseases in elderly as well as in early age.&#x0D; Results: 41 (82%) patients were male and 9 (18%) patients were female. Serum homocysteine level was higher in group I than group II (71.4% vs. 40.9%). Besides, the level of mean serum homocysteine level was significantly (p=0.02) higher in group I than group II (21.18±9.53 vs. 17.24±8.92 μmol/L).&#x0D; Conclusion: In conclusion, this study suggests that serum homocysteine has an association with early onset atherosclerotic PAOD. Therefore, a raised serum homocysteine level can be used as an independent biochemical predictor of early onset atherosclerotic PAOD.&#x0D; Cardiovasc. j. 2021; 13(2): 120-127

Homocysteine, the methylenetetrahydrofolate reductase 677C>T polymorphism and hypertension: effect modifiers by lifestyle factors and population subgroups.

Evidence linking fasting plasma total homocysteine (tHcy) and methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype with hypertension is inconsistent. Differences in B vitamin status, other lifestyle factors or their consideration in analyses might explain this. We investigated these associations in the absence of mandatory fortification with folic acid and B vitamin supplement use. A cross-sectional study was conducted in 788 adults, aged 18-75 years, randomly selected from three Catalonian town population registers. Fasting plasma folate, cobalamin, tHcy, erythrocyte folate, erythrocyte glutathione reductase activation coefficient (EGRAC, functional riboflavin status indicator; increasing EGRAC indicates worsening riboflavin status), MTHFR 677C>T and solute carrier family 1 (SLC19A1) 80 G>A genotypes were determined. Medical history and lifestyle habits were recorded. Principal tHcy determinants differed between women (age, plasma folate, plasma cobalamin, cigarettes/d) and men (MTHFR 677TT genotype, plasma folate, plasma cobalamin and CT genotype). The MTHFR 677C>T polymorphism-tHcy association (β standardised regression coefficients) was stronger in male smokers (0·52, P < 0·001) compared with non-smokers (0·21, P = 0·001) and weaker in participants aged >50 years (0·19, P = 0·007) compared with ≤50 years (0·31, P < 0·001). Hypertension was more probable in the third tHcy tertile compared with other tertiles (OR 1·9; 95 % CI 1·2, 3·0), and in participants aged ≤50 years, for the MTHFR 677TT genotype compared with the CC genotype (OR 4·1; 95 % CI 1·0, 16·9). EGRAC was associated with increased probability of hypertension in participants aged >50 years (OR 6·2; 95 % CI 1·0, 38·7). In conclusion, moderately elevated tHcy and the MTHFR 677CT genotype were associated with hypertension. The MTHFR 677C>T genotype-hypertension association was confined to adults aged ≤50 years.

Moderately elevated first trimester fasting plasma total homocysteine is associated with increased probability of miscarriage. The Reus-Tarragona Birth Cohort Study

The association between elevated early pregnancy fasting plasma total homocysteine (tHcy) and miscarriage risk was investigated prospectively in participants (n = 544) from the Reus-Tarragona Birth Cohort study. Pregnancy was confirmed before 12 gestational weeks (GW) by ultrasound scan and a fasting blood sample collected. Pregnancies with complications other than miscarriages were excluded. Miscarriages were diagnosed by ultrasound scan and gestational age at the time of miscarriage estimated by embryo size, where possible. Cases in which blood samples were collected more than a week after the miscarriage, or the miscarriage was of known cause, were excluded.Fasting plasma folate, vitamin B12, tHcy, cotinine (biomarker of smoking), red blood cell (RBC) folate, MTHFR 677C > T (rs1801133) and SLC19A1 80G>A (rs1051266) genotypes were determined.The exposed group consisted of participants with first trimester tHcy ≥ P90 (7.1 μmol/L) (n = 57) and unexposed of those with tHcy < P90 (n = 487). Adherence to folic acid supplement recommendations, plasma folate, plasma vitamin B12, RBC folate and prevalence of optimal RBC folate status (≥ 906 μmol/L) were lower in the exposed compared to unexposed group. The prevalences of the MTHFR 677 TT genotype and miscarriage were higher in the exposed group. The relative risks (95% CI) of pregnancy ending in miscarriage were 2.5 (1.1, 5.7) and 2.1 (1.0, 4.5) for participants in the high tHcy and suboptimal RBC folate groups (compared to the reference groups) respectively. Adherence to folic acid supplement recommendations was positively associated, while the MTHFR 677 TT versus CC genotype and smoking versus non-smoking were negatively associated, with RBC folate status.

Moderately elevated preconception fasting plasma total homocysteine is a risk factor for psychological problems in childhood.

We investigated the effect of maternal preconception fasting plasma total homocysteine (tHcy) on psychological problems in children aged 6 years from normal pregnancies. A longitudinal study was carried out from preconception, throughout each trimester of pregnancy, until 6 years of age in the offspring. Fasting blood samples at 2-10 weeks preconception and non-fasting samples at birth were collected. Parents completed the Child Behaviour Checklist (CBCL) and teachers the Inattention-Overactivity with Aggression (IOWA) scale for the 6-year-old children. Elevated tHcy during pregnancy has been associated with several adverse outcomes and with neurodevelopmental impairment in the offspring.ParticipantsThe initial sample consisted of 139 healthy non-pregnant women who were planning on becoming pregnant. Eighty-one mother-child dyads were followed from preconception until 6 years of age. After adjusting for covariables, multiple linear regression models showed that higher preconception tHcy was associated with higher scores in internalizing dimension (β=0·289; P=0.028), specifically in withdrawn behaviour (β=0·349; P=0·009), anxiety/depression (β=0·303; P=0·019) and social problems (β=0·372; P=0·009). Aggressive behaviour in the school setting was higher in children whose mothers had higher preconception tHcy (β=0·351; P=0·014). Moderately elevated preconception tHcy may increase the risk of psychological problems in offspring during childhood. These findings add to the evidence that maternal nutritional status, even before being pregnant, can affect later offspring health and may be important to consider when developing future public health policy.

Small Vessel Cerebrovascular Pathology Identified by Magnetic Resonance Imaging Is Prevalent in Alzheimer's Disease and Mild Cognitive Impairment: A Potential Target for Intervention.

There is evidence that Alzheimer's disease (AD) has significant cerebrovascular etiopathogenesis. Understanding potentially modifiable risk factors for vascular disease can help design long-term intervention strategies for controlling or preventing cognitive dysfunction attributable to cerebrovascular disease. To evaluate the presence and severity of markers of cerebrovascular pathology, its relationship to diagnostic categories of dementia, including AD, and association with the metabolic biomarker homocysteine. In a cross-sectional observational study, 340 community-dwelling elders received a clinical evaluation including brain MRI and neuropsychological tests. Dementia and mild cognitive impairment (MCI) were diagnosed by consensus committee. Fasting total plasma homocysteine was measured. Statistical analyses were adjusted for demographics and cerebrovascular risk factors. Nearly 25% of those diagnosed with AD had small vessel infarcts (SVI). Periventricular white matter hyperintensity (pvWMHI) was prevalent in participants with AD (61%) or MCI (amnesic 61% and non-amnesic 54%, respectively). Participants with SVI and/or pvWMHI also had greater brain atrophy. Homocysteine concentrations were higher in individuals with cerebrovascular findings than in those without. In individuals with cerebrovascular disease, homocysteine was inversely related to executive function (p = 0.022) and directly related to degree of brain atrophy (p = 0.009). We demonstrated a significant prevalence of small vessel markers of cerebrovascular pathology in individuals diagnosed with AD, with a significant concurrence between cerebrovascular disease and brain and ventricular atrophy. While current research on AD has focused on amyloid-βpeptide deposition, tau-pathology, and microglial activation and inflammation, greater attention to the cerebrovascular contribution to this neurodegenerative disease presents an additional target for therapeutic prevention and intervention.

Plasma homocysteine levels, methylene tetrahydrofolate reductase A1298C gene polymorphism and risk of retinal vein thrombosis.

There are limited data regarding the role of methylene tetrahydrofolate reductase (MTHFR) A1298C polymorphism and hyperhomocysteinemia as risk factors for retinal vein thrombosis (RVT) in Iranians. This study aimed to examine a possible association between fasting plasma total homocysteine (tHcy) levels, MTHFR A1298C polymorphism and RVT development in Iranian patients. Our study population consisted of 73 patients with a diagnosis of RVT (52.7 ± 16.2 years) and 73 age and sex-matched healthy controls (49.1 ± 14.6 years). Genotyping for the MTHFR A1298Cpolymorphism was conducted by PCR-RFLP technique and plasma tHcy levels were measured by an enzyme immunoassay method. Fasting plasma tHcy levels were 20.29 ± 8.5 μmol/l in RVT patients and 10.9 ± 3.1 μmol/l in control subjects. The number of cases with abnormal tHcy values (hyperhomocysteinemia) was significantly higher in the RVT patients than control subjects (P = 0.0001). The prevalence of MTHFR 1298CC homozygote genotype was similar in RVT patients and controls (17.8 vs.15.1%, P = 0.45). There were no significant differences in genotype distribution of MTHFR A1298C polymorphism between males and females in both RVT patients and controls (P > 0.05). The frequency of the 1298C allele was 39.1 and 35.6% in patients and controls, respectively, and did not differ significantly between them (P = 0.23). Moreover, heterozygote and homozygote genotypes in the RVT patients had significantly higher abnormal tHcy values than corresponding genotypes in control subjects (P < 0.001). Our study demonstrated that hyperhomocysteinemia but not homozygosity for MTHFR A1298C polymorphism is a significant risk factor for RVT in the Iranian population.

Association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and susceptibility to Graves' ophthalmopathy.

The pathogenesis of Graves' ophthalmopathy (GO) remains to be entirely elucidated. The present study aimed to determine the association between phenotypic expression of the MTHFR gene and susceptibility to GO in patients with Graves' disease (GD). A prospective case‑controlled study was conducted with 122patients with GD and GO (n=72) or without GO (n=50) and 100healthy controls in South Korea. Patient history, including smoking, nutritional status, thyroid function and antithyroid antibodies were investigated and clinical activity score, VISA classification (which includes vision, inflammation, strabismus and appearance/exposure) and orbit computed tomography were evaluated. Fasting plasma total homocysteine (tHcy) concentration was measured, and genotype analysis of the MTHFR gene was conducted. The TT homozygous genotype was associated with a two‑fold increased risk of GO [adjusted odds ratio (AOR), 2.19; 95% confidence interval (CI), 0.78‑6.14]. However, this result was not significant. The TT genotype significantly increased the risk of GO compared with that in healthy controls (AOR, 2.92; 95% CI, 1.11‑7.65). The MTHFR 677CT/1298AA genotype decreased the risk of GO in patients with GD (AOR, 0.26; 95% CI, 0.08‑0.91). tHcy levels in patients with GD without GO were significantly higher than in patients with GO, however, they were within the normal limit. The current study identified an association between MTHFR polymorphisms and GO. These results will aid understanding of the pathogenesis of GO and facilitate development of genetic therapeutic strategies.

Moderately elevated maternal homocysteine at preconception is inversely associated with cognitive performance in children 4 months and 6 years after birth.

Prenatal methyl donor deficiency leads to homocysteine accumulation in the brain and impaired neurodevelopment in rats. We investigated the effect of moderately elevated preconception fasting total plasma homocysteine (tHcy) on child neurodevelopment in a prospective study of 67 and 76 mother-child pairs at 4 months and 6 years of age, respectively. Fasting blood samples at 2-10 weeks preconception, from the cord (nonfasting) and the mother and child 6 years after birth, were collected. Psychomotor and mental development were assessed at 4 months using the Bayley Scale of Infant Development (BSID) and cognitive development at 6 years using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI). Highest tertile preconception tHcy (≥9.04 µmol/L) was categorized as moderately elevated and low-mid tertile tHcy as normal. Children, born to mothers with moderately elevated compared to normal preconception tHcy, scored lower [mean (95% CI)] in the BSID psychomotor [115 (105, 124) vs. 126 (121, 130), p = 0.03] and mental [101 (93, 109) vs. 113 (107, 119), p = 0.03] development tests. Multiple logistic regression analysis showed that moderately elevated compared to normal preconception tHcy was associated with greater probability, OR (95%CI), of scoring in the lowest tertile for BSID psychomotor development (≤120): 4.0 (1.1, 14.3) and lowest tertiles for WPPSI full (≤111), verbal (≤104) and performance (≤111), intellectual quotient: 6.0 (1.5, 23.7), 3.5 (1.1, 11.2) and 4.1 (1.1, 15.7), respectively. We conclude that moderately elevated preconception tHcy is inversely associated with psychomotor and cognitive development scores in infants and children.

Early pregnancy B vitamin status, one carbon metabolism, pregnancy outcome and child development.

Periconception supplementation with folic acid is recommended until 12 gestational weeks to prevent neural tube defects. Doses of folic acid contained in supplements and timing and length of use during pregnancy vary. The effects of status in periconception and pregnancy folate, cobalamin, betaine and their interactions on one carbon metabolism (1C), as well as the global effect of 1C on foetal growth and pregnancy outcome, are reviewed. Results from prospective studies are reviewed. Cessation of folic acid supplement use after the first trimester is associated with a sharp drop in plasma folate status and enhanced conversion of betaine to dimethylglycine. Dimethylglycine production is also higher in mothers with low folate status than in those with normal-high folate status. The effects of high doses of folic acid on one carbon metabolism in mothers with low early pregnancy cobalamin status and on foetal growth are also reviewed. Several studies report that moderately elevated early pregnancy fasting plasma total homocysteine (tHcy) is inversely associated with birth weight and a predictor of intrauterine growth retardation. There is also evidence for increased risk of preterm birth when maternal folate status is low.

Riboflavin status modifies the effects of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms on homocysteine.

Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), riboflavin-dependent enzymes, participate in homocysteine metabolism. Reported effects of riboflavin status on the association between the MTHFR 677C>T polymorphism and homocysteine vary, and the effects of the MTRR 66A>G or MTRR 524C>T polymorphisms on homocysteine are unclear. We tested the hypothesis that the effects of the MTHFR 677C>T, MTRR 66A>G and MTRR 524C>T polymorphisms on fasting plasma total homocysteine (tHcy) depend on riboflavin status (erythrocyte glutathionine reductase activation coefficient, optimum: <1.2; marginally deficient: 1.2-1.4; deficient: ≥1.4) in 771 adults aged 18-75years. MTHFR 677T allele carriers with middle or low tertile plasma folate (<14.7nmol/L) had 8.2% higher tHcy compared to the 677CC genotype (p<0.01). This effect was eliminated when riboflavin status was optimal (p for interaction: 0.048). In the lowest cobalamin quartile (≤273pmol/L), riboflavin status modifies the relationship between the MTRR 66 A>G polymorphism and tHcy (p for interaction: 0.034). tHcy was 6.6% higher in MTRR 66G allele carriers compared to the 66AA genotype with marginally deficient or optimal riboflavin status, but there was no difference when riboflavin status was deficient (p for interaction: 0.059). tHcy was 13.7% higher in MTRR 524T allele carriers compared to the 524CC genotype when cobalamin status was low (p<0.01), but no difference was observed when we stratified by riboflavin status. The effect of the MTHFR 677C>T polymorphism on tHcy depends on riboflavin status, that of the MTRR 66A>G polymorphism on cobalamin and riboflavin status and that of the MTRR 524C>T polymorphism on cobalamin status.

Plasma homocysteine concentrations in acute and convalescent changes of central retinal vein occlusion in a Chinese population.

Homocysteine is a potential risk factor for central retinal vein occlusion (CRVO), but this remains controversial. We measured fasting total plasma homocysteine (tHcy) concentrations immediately after CRVO and in the convalescent period to investigate this controversy. We measured fasting tHcy concentrations in 36 consecutive patients with CRVO within three days; and at 1, 3, and 6 months after CRVO; and once in 36 control subjects. The vitamin B12 and folate levels, and the presence of C677T MTHFR polymorphisms, were analyzed in all patients and controls. Median tHcy concentrations were not significantly higher than in matched control subjects in the acute phase of CRVO (9.66 [10.75 ± 4.09] vs. 9.25 [9.96 ± 4.02] μmol/L, P = 0.371) and 1 month after CRVO (P = 0.119). However, tHcy levels increased significantly in the convalescent period and were significantly higher than in control subjects at 3 CRVO (P = 0.010) and 6 (P < 0.001) months after CRVO. Furthermore, tHcy levels of the ischemic CRVO patients at 6 months after CRVO were significantly higher than in nonischemic CRVO patients (P = 0.028). However, these observations did not appear to be explained by alteration in serum folate, vitamin B12 concentrations, and the MTHFR C677T genotype. The tHcy levels are not immediately elevated after CRVO, but increase in the convalescent period. These data do not support the hypothesis that raised tHcy concentrations are independent risk factor for CRVO. Instead, it is possible that elevated tHcy levels may be caused by the disease process itself.

Dose–response effects of oral guanidinoacetic acid on serum creatine, homocysteine and B vitamins levels

Guanidinoacetic acid (GAA) is an intermediate in the biosynthesis of creatine (Cr), yet its use in human nutrition is limited due to a lack of a clear understanding of its' dose-response effect. Thus, the purpose of this study was to investigate the effect of three different dosages of GAA (1.2, 2.4 and 4.8 g/day) administered for 6 weeks on serum and urinary variables related to GAA metabolism. Forty-eight healthy volunteers participated in the randomized, placebo-controlled, double-blind, repeated-measure study. At baseline, after 1, 2, 4 and 6 weeks, participants provided both fasting blood samples and 24-h urine. GAA intervention significantly increased serum and urinary GAA, Cr and creatinine as compared to placebo (P < 0.05). Differences were found for serum GAA and Cr responses between the three GAA dosages, with high-dose GAA resulting in a greater increase (P < 0.05) in the plasma concentration of both variables as compared to other GAA dosages. In GAA groups, fasting plasma total homocysteine (T-Hcy) increased by 3.5 μmol/L on average at post-administration, yet no dose-response differences were found between trials. Serum B vitamins were not affected by either placebo or GAA intervention (P > 0.05). Results indicate that low-to-high dosages of exogenous GAA can increase serum concentrations of Cr and T-Hcy while not depleting the B vitamins pool available for remethylation of homocysteine. ClinicalTrials.gov, identification number NCT01133899.

A Cross-Sectional Study to Find Out the Relationship of Methylenetetrahydrofolate Reductase (MTHFR) C677T Genotype with Plasma Levels of Folate and Total Homocysteine by Daily Folate Intake in Japanese

In those with the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype, enzyme activity is lowered. Therefore, these individuals might require an increased intake of folate to maintain or control blood levels of plasma folate or total homocysteine (tHcy). We examined associations of dietary folate intake with fasting plasma folate and total homocysteine (tHcy) according to genotype among 554 Japanese (207 men and 347 women aged 39-89 y) recruited in 2009. Intake of folate was estimated with a food frequency questionnaire. The MTHFR polymorphism was genotyped by a polymerase chain reaction with confronting two-pair primers. The log-transformed concentration of folate or tHcy was regressed on energy-adjusted folate intake in a linear regression analysis. Higher folate intake was associated with higher plasma folate among those with the CC (β=0.165, p=0.066) or CT (β=0.248, p<0.001) genotypes, and with lower tHcy levels only among those with the CC (β=-0.141, p=0.013) genotype. Plasma folate was significantly and inversely associated with tHcy, irrespective of MTHFR genotype. When the analysis was restricted to those with tHcy levels higher than the reference range (≥13.5 nmol/mL, n=20), these significant associations were not found. The interaction between folate intake or plasma folate and genotype was not significant in any analysis. In conclusion, dietary folate intake was positively associated with plasma folate among those with the CC or CT genotypes and inversely associated with tHcy among those with the CC genotype, but the associations were not clear among those with higher levels of tHcy.

Low folate status enhances pregnancy changes in plasma betaine and dimethylglycine concentrations and the association between betaine and homocysteine

Folate, choline, and betaine participate in homocysteine metabolism. It is not known whether they interact during pregnancy. The objective was to investigate how folate status affects choline, betaine, and dimethylglycine during pregnancy. Fasting plasma folate, cobalamin, free choline, betaine, dimethylglycine, and total homocysteine (tHcy) were measured longitudinally at <12, 15, 24-27, and 34 gestational weeks (GW); at labor (nonfasting); and in the cord in participants (n = 522) from the Reus-Tarragona Birth Cohort (NUTrició i Creixement Intrauterí Retardat phase). Timing, dose, and duration of folic acid supplement use were recorded. Folate status was classified as below (low) or above (high) median plasma folate at baseline (27.6 nmol/L) and at 24-27 GW (11.4 nmol/L). Associations between folate or betaine with tHcy were investigated by using multiple linear regression analysis. Plasma betaine decreased by 34.8% (1.0%) throughout pregnancy, and dimethylglycine increased by 39.7% (2.7%) between 24-27 GW and labor (all P < 0.001). Compared with high folate status, low status was associated with a higher dimethylglycine/betaine ratio from 15 GW and with lower plasma betaine and higher dimethylglycine from 24 to 27 GW, for the rest of pregnancy. Regression analysis showed that by 24-27 GW, both plasma folate and betaine were inversely associated with tHcy when folate status was low and that the association between betaine and tHcy depended on folate status at 24-27 and 34 GW (interaction terms: P < 0.001 and P < 0.01). Betaine was inversely associated with tHcy at labor regardless of folate status. Low folate status enhances the reduction in betaine and the increase in dimethylglycine during pregnancy and strengthens the association between betaine and tHcy. This trial was registered at clinicaltrials.gov as NCT01778205.

Assessment of atherosclerosis risk due to the homocysteine–asymmetric dimethylarginine–nitric oxide cascade in children taking antiepileptic drugs

PurposeThe aim of this study was to assess the atherogenicity risk of antiepileptics in children by investigating the cascade, “hyperhomocysteinemia (HHcy)→asymmetric dimethylarginine (ADMA) increase→nitric oxide (NO) decrease”, which is thought to contribute to the developmental process of atherosclerosis. MethodsThe participants included 53 epilepsy patients who received either valproic acid (VPA, n=26) or oxcarbazepine (OXC, n=27). Twenty-four healthy sex- and age-matched children served as controls. Fasting plasma total homocysteine (tHcy), ADMA and NO levels were measured. ResultsThe differences in Hcy, ADMA, NO, vitamin B12 and folate levels between VPA, OXC and control groups were all insignificant (p>0.05 for all). In the patient group (VPA and OXC groups), 22.6% of the children (12/53) had tHcy levels above the normal cutoff (13.1μmol/l) for children and 17% of the children (9/53) had tHcy levels of greater than 15μmol/l which is accepted as the critical value for an increased atherosclerosis risk (p<0.05 for both). The difference in rate of HHcy between VPA and OXC groups was statistically insignificant (p>0.05, for both cut off levels of HHCy). There was a positive correlation of tHcy levels and antiepileptic drug treatment duration in the patient group (r=+0.276, p<0.05). ConclusionHHcy may develop in patients using OXC. Contrary to some previous publications, our data do not suggest that OXC is safer than VPA in terms of HHcy risk. Further prospective, large scale and longer term studies investigating all suggested pathways responsible for development of atherosclerosis due to HHcy should be conducted to define the exact mechanism responsible for AEDs related atherosclerosis.

Plasma homocysteine level and its relationship to clinical profile in Parkinson's disease patients at the Lagos University Teaching Hospital.

Hyperhomocysteinaemia (HHcy) is as a long-term sequelum of levodopa therapy in Parkinson's disease (PD). Information on its frequency and effects in Africans with PD is sparse. To determine the frequency of HHcy and its relationship to clinical features of PD in African patients. Using a case-control design, 40 consecutively attending PD patients and 40 age- and gender-matched healthy volunteering controls were studied. Parkinson's disease cases were evaluated for disease and treatment characteristics, using the Unified Parkinson Disease Rating Scale (UPDRS) motor and activities of daily living scores and disease stage (Hoehn and Yahr scale). Fasting total plasma homocysteine (Hcy) was determined in all subjects. Hyperhomocysteinaemia was defined as a Hcy level above the 90th percentile for the controls. Mean Hcy was 13.8 ± 5.4mmol/L in PD and 12.4±3mmol/L in controls (P>0.05). Hyperhomocysteinaemia (Hcy > 16.26umol/L) occurred in nine (22.5%) PD patients (all on levodopa) and 6 (15%) controls (P>0.05). Mean duration of levodopa use was 92 ± 105.3 months in PD with HHcy compared to PD patients with normal Hcy 33.9 ± 33.2 (p < 0.05). Disease severity and disability were similar regardless of Hcy levels. None of current age, disease duration, Hoehn and Yahr stage, UPDRS scores, total levodopa dose and duration was independent predictor of homocysteine level. There is increased occurrence of hyper-homocysteinaemia in Nigerian subjects with Parkinson's disease, receiving Levodopa. This hyperhomocysteinaemia is more common with prolonged use but appears to have no relationship with disease severity or disability.

The A1298C Mutation in Methylenetetrahydrofolate Reductase Gene and Its Association With Idiopathic Venous Thrombosis in an Iranian Population

Background: Venous thrombosis (VT) is an important cause of mortality and morbidity resulting from acquired and inherited factors. The A1298C mutation of the methylenetetrahydrofolate reductase (MTHFR) gene remains a controversial risk factor for VT. In this study we investigated a possible association between A1298C mutation in the MTHFR gene and fasting hyperhomocysteinemia with VT. Materials and Methods: The study was comprised of 200 patients with a diagnosis of VT and 100 healthy subjects as a control. A1298C mutation analysis was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and homocysteine measurement was carried out by enzyme immunoassay. Results: The prevalence of A1298C genotypes between patients and controls was almost similar (P=0.9). The frequency of the 1298C allele was 38.5% and 36.5% in patients and controls, respectively, and did not differ significantly between the 2 groups (odds ratio [OR], 0.811, 95% CI [0.566-1.183], P=0.29). The fasting plasma total homocysteine level was significantly higher in patients than controls (P=0.001). Conclusions: We concluded that hyperhomocysteinemia but not MTHFR A1298C mutation is a significant risk factor for VT in the Iranian population.

Relationship between Insulin Resistance and Inflamation Markers in Hemodialysis Patients

Objective. The prevalence and risk factors of cardiovascular disease (CVD) are increasing in end stage renal disease (ESRD) patients. In this study, we sought to research the relationship between the insulin resistance, which is one of the risk factors for CVD, and the inflammation markers, especially C-reactive protein, fibrinogen, uric acid, and homocysteine levels in our patients who were recently diagnosed with ESRD and started hemodialysis. Materials and methods. 64 HOMA-IR-positive and 114 HOMA-IR-negative patients were enrolled in this study. Blood samples were obtained from the patients for fasting plasma glucose, insulin, CRP, fibrinogen, uric acid, total homocysteine, urea, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride, total protein, and albumin analysis after physical examinations and anamnesis were completed. Results. Fibrinogen and CRP levels of HOMA-IR-positive HD patients were significantly increased compared to non-insulin resistants. Furthermore, there is significant positive relationship between insulin resistance and serum CRP and fibrinogen levels in these HOMA-IR-positive HD patients (r = 0.258, p < 0.001). Conclusion. We found out that the fibrinogen and CRP levels are significantly high in HOMA-IR positive HD patients, according to determine the risk ratio for coronary artery disease in HD patients, and think that an assessment of insulin resistance is necessary.