Higher tHcy Levels Research Articles

The Impact of Cardiovascular Disease Gene Polymorphism and Interaction with Homocysteine on Deep Vein Thrombosis.

Deep vein thrombosis (DVT) affects vascular health and can even threaten life; however, its pathogenesis remains unclear. Cardiovascular disease (CVD) and DVT share common risk factors, such as dyslipidemia, aging, etc. We aimed to investigate the loci of published CVD susceptibility genes and their association with environmental factors that might be related to DVT. Genotyping by Kompetitive Allele Specific PCR (KASP), collection of lifestyle information, and determination of blood biochemical markers were performed in 165 DVT cases and 164 controls. The impact of six single nucleotide polymorphisms (SNPs) and additional potential variables on DVT morbidity was evaluated using unconditional logistic regression (ULR). To explore the high-order interactions related to genetics and the body's internal environment exposure that affect DVT, ULR, crossover analysis, and multifactor dimensionality reduction/generalized multifactor dimensionality reduction (MDR/GMDR) were employed. Sensitivity analyses were performed using the EpiR package. The polymorphisms of FGB rs1800790 and PLAT rs2020918 were significantly associated with DVT. The optimum GMDR interaction model for gene-gene (G × G) consisted of THBD rs1042579, PLAT rs2020918, and PON1 rs662. The PLAT rs2020918 and MTHFR rs1801133 polymorphisms together eliminated the maximum entropy by the MDR method. The optimum GMDR interaction model for gene-environment (G × E) consisted of MTHFR rs1801133, FGB rs1800790, PLAT rs2020918, PON1 rs662, and total homocysteine (tHcy). Those with high tHcy levels and three risk genotypes significantly increased the DVT risk. In conclusion, certain CVD-related SNPs and their interactions with tHcy may contribute to DVT. These have implications for investigating DVT etiology and developing preventive treatment plans.

One-carbon metabolism biomarkers and upper gastrointestinal cancer in the Golestan Cohort Study.

Incidence of esophageal and gastric cancer has been linked to low B-vitamin status. We conducted matched nested case-control studies of incident esophageal squamous cell carcinoma (ESCC; 340 case-control pairs) and gastric cancer (GC; 352 case-control pairs) within the Golestan Cohort Study. The primary exposure was plasma biomarkers: riboflavin and flavin mononucleotide (FMN) (vitamin B2), pyridoxal phosphate (PLP) (B6), cobalamin (B12), para-aminobenzoylglutamate (pABG) (folate), and total homocysteine (tHcy); and indicators for deficiency: 3-hydroxykyurenine-ratio (HK-r for vitamin B6) and methylmalonic acid (MMA for B12). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression adjusting for matching factors and potential confounders. High proportions of participants had low B-vitamin and high tHcy levels. None of the measured vitamin B levels was associated with the risk of ESCC and GC, but elevated level of MMA was marginally associated with ESCC (OR = 1.42, 95% CI = 0.99-2.04) and associated with GC (OR = 1.53, 95% CI = 1.05-2.22). Risk of GC was higher for the highest versus lowest quartile of HK-r (OR = 1.95, 95%CI = 1.19-3.21) and for elevated versus non-elevated HK-r level (OR = 1.59, 95% CI = 1.13-2.25). Risk of ESCC (OR = 2.81, 95% CI = 1.54-5.13) and gastric cancer (OR = 2.09, 95%CI = 1.17-3.73) was higher for the highest versus lowest quartile of tHcy. In conclusion, insufficient vitamin B12 was associated with higher risk of ESCC and GC, and insufficient vitamin B6 status was associated with higher risk of GC in this population with prevalent low plasma B-vitamin status. Higher level of tHcy, a global indicator of OCM function, was associated with higher risk of ESCC and GC.

Linking biomarkers with healthy lifestyle outcomes after stroke: Supplementary results of a 12-month randomized controlled trial

Background and aimsParticipation in a healthy lifestyle intervention such as the Diabetes Prevention Program Group Lifestyle Balance–adapted for stroke (GLB-CVA) may reduce stroke burden. Identifying biomarkers associated with lifestyle changes may enhance an individualized approach to stroke recovery. We investigated metabolic biomarkers related to cardiovascular and neurological function in individuals with stroke in the GLB-CVA study and healthy (non-stroke) individuals. Methods and resultsParticipants with chronic (>12 months) stroke were recruited to this wait-list randomized controlled trial if they were overweight (BMI ≥25 kg/m2). Participants were randomized to (1) the GLB-CVA program to complete 22 educational sessions addressing behavioral principals of dietary and physical activity or (2) a 6 month wait-list control (WLC). Biomarkers [Plasma irisin, vascular endothelial growth factor, lipoprotein-associated phospholipase A2 (Lp-PLA2), insulin-like growth factor 1 and brain-derived neurotrophic factor (BDNF)] were collected at baseline, 3, and 6 months. Age-matched healthy individuals were recruited for biomarker assessment. Compared to healthy adults (n = 19), participants with stroke (GLB-CVA = 24; WLC = 24) at baseline had higher tHcy levels (p < 0.001) and lower PLA2 levels (p = 0.016). No statistically significant interactions were observed for any biomarkers between the GLB-CVA and WLC or between people who achieved 5% weight loss and those who did not. ConclusionParticipation in a 6-month healthy lifestyle program did not result in statistically significant changes to select metabolic biomarker levels for our participants with chronic stroke. However, participants with stroke demonstrated a unique biomarker profile compared to age-matched healthy individuals.

Associations of serum 25-hydroxyvitamin D with serum folate, cobalanin, and homocysteine concentrations and methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in healthy adults.

The aim of this study was to investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] with various demographic, anthropometric, and genetic characteristics and biochemical parameters in healthy Greek adults. Demographic (age and sex), anthropometric (body mass index/BMI), and genetic (MTHFR gene polymorphisms) characteristics and biochemical parameters (serum folate, cobalamin/Cbl, and total homocysteine/tHcy concentrations), which had been recorded and measured, among others, in the framework of periodic medical examination (military personnel) or check-up (non-military personnel) of 383 healthy Greek adults (199 men and 184 women) were analyzed. Serum 25(OH)D, tHcy, folate, and Cbl levels were determined using immunoassay methods. The MTHFR C677T and A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. Serum 25(OH)D concentrations were correlated with Cbl levels and MTHFR C677T gene polymorphism, while they had a reverse correlation with serum tHcy levels, age, and BMI. There was no significant correlation between serum 25(OH)D concentrations and sex, serum folate levels, and smoking status. Individuals with the 677TT genotype had statistically significantly lower serum 25(OH)D levels than those with the 677CC or 677CT genotype, while individuals with the 1298CC genotype had statistically significantly higher serum 25(OH)D levels than those with 1298AA or 1298AC genotype. Moreover, the reverse correlation between the serum 25(OH)D and tHcy levels was statistically significant in all six MTHFR genotypes. Serum 25(OH)D levels are associated with age, BMI, serum tHcy, and Cbl levels and MTHFR C677T gene polymorphism. The most significant finding of our study is the observed reverse correlation of serum 25(OH)D levels with serum tHcy levels. Considering that vitamin D deficiency and hyperhomocysteinemia (HHcy) are associated with an increased risk for cardiovascular diseases (CVDs), we suggest that individuals with high serum tHcy levels should be further investigated for, inter alia, their serum 25(OH)D levels.

INFLUENCE OF THE METHYLENE TETRAHYDROFOLATE REDUCTASE (MTHFR) GENE POLYMORPHISMS ON SERUM FOLATE, COBALANIN AND HOMOCYSTEINE LEVELS IN HEALTHY GREEK ADULTS

Objective: Methylene tetrahydrofolate reductase (MTHFR) is a key enzyme of homocysteine metabolism participating in the folate cycle. It is well known that hyperhomocysteinemia is associated with an increased risk for cardiovascular disease. The aim of this study was to investigate the association of MTHFR C677T and MTHFR A1298C gene polymorphisms with serum folate, cobalamin (Cbl) and homocysteine (Hcy) concentrations in healthy Greek adults. Design and method: The MTHFR C677T and A1298C gene polymorphisms were genotyped in 383 healthy Greek adults (199 men; mean age±SD: 37.3±8.2 years) using polymerase chain reaction and reverse hybridization. Serum folate, Cbl and total Hcy (tHcy) levels were determined using immunoassays methods. Results: Among the 383 individuals, 73 (19.1%) were normal (CC), 202 (52.7%) were heterozygous (CT) and 108 (28.2%) were homozygous (TT) regarding the MTHFR C677T gene polymorphism, while 263 (68.7%) were normal (AA), 105 (27.4%) were heterozygous (AC) and 15 (3.9%) were homozygous (CC) regarding the MTHFR A1298C gene polymorphism. The overall C and T allele frequency for the MTHFR C677T gene polymorphism was 45.4% and 54.6%, respectively, while the overall A and C allele frequency for the MTHFR A1298C gene polymorphism was 82.3% and 17.6%, respectively. The individuals with 677TT genotype had significantly lower serum folate and significantly higher serum tHcy levels than individuals with 677 CC or CT genotypes. On the contrary, the A1298C gene polymorphism had no significantly influence on serum folate and tHcy levels. Conclusions: Serum folate and tHcy levels are influenced by the existence of the MTHFR C677T gene polymorphism (mainly 677TT genotype). Individuals with low serum folate levels and/or high serum tHcy levels should be further investigated for a possible existence of MTHFR C677T and not A1298C gene polymorphisms, with aim to determine the suitable treatment.

Vitamin B12, Folate, Homocysteine, Inflammatory Mediators (Interleukin-6, Tumor Necrosis Factor-α and C-Reactive Protein) Levels in Adolescents with Anxiety or Depressive Symptoms.

To evaluate the prevalence of abnormal vitamin B12, folate, total homocysteine (tHcy), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) levels, to analyze the relationship between these parameters and the severity of anxiety or depressive symptoms, and to explore the possible factors associated with abnormal levels of these parameters in adolescents with anxiety or depressive symptoms. Adolescent (aged 12-18 years) outpatients with anxiety or depressive symptoms were recruited. The patient health questionnaire-9 and generalized anxiety disorder scale-7 were used to measure the severity of depression and anxiety. Serum vitamin B12, folate, tHcy, IL-6, TNF-α, and CRP levels were determined. 128 subjects were recruited. The prevalence of vitamin B12 and folate deficiency, tHcy, TNF-α, IL-6, and CRP elevation was 8.6%, 10.2%, 25.8%, 14.8%, 21.9%, and 10.2%, respectively, in adolescents with anxiety or depressive symptoms. Lower vitamin B12 levels were correlated with a higher risk of severe anxiety and depressive symptoms. The severity of some symptoms of anxiety or depression were weakly correlated with vitamin B12, folate, tHcy, IL-6, and CRP levels. Vitamin B12, folate, and tHcy levels were not associated with inflammatory mediators. Vitamin B12 deficiency was associated with older age and higher tHcy levels. Folate deficiency was associated with elevatedtHcy. ElevatedtHcy was associated with lower vitamin B12 and folate levels. IL-6 elevation was associated with elevated CRP and TNF-α. CRP elevation was associated with older age, higher BMI, and current drinking. Lower vitamin B12 levels were correlated with a higher risk of severe anxiety or depressive symptoms. Weak correlations were observed between the severity of some symptoms of anxiety or depression and vitamin B12, folate, tHcy, IL-6, and CRP levels. Vitamin B12, folate, and tHcy levels were related to each other. IL-6 elevation was associated with elevated CRP and TNF-α. CRP elevation was associated with older age, higher BMI, and current drinking.

Association of methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms with serum folate, cobalanin and homocysteine concentrations in Greek adults

Methylene tetrahydrofolate reductase (MTHFR) is a key enzyme of homocysteine metabolism participating in the folate cycle. The aim of this study was to investigate the association of MTHFR C677T and MTHFR A1298C gene polymorphisms with serum folate, cobalamin (Cbl) and homocysteine (Hcy) concentrations in healthy Greek adults. The MTHFR C677T and A1298C gene polymorphisms were genotyped in 383 healthy Greek adults (199 men and 184 women) using polymerase chain reaction and reverse hybridization. Serum folate, Cbl and total Hcy (tHcy) levels were determined using immunoassays methods. Among the 383 individuals, 73 (19.1%) were normal (CC), 202 (52.7%) were heterozygous (CT) and 108 (28.2%) were homozygous (TT) regarding the MTHFR C677T gene polymorphism, while 263 (68.7%) were normal (AA), 105 (27.4%) were heterozygous (AC) and 15 (3.9%) were homozygous (CC) regarding the MTHFR A1298C gene polymorphism. The overall C and T allele frequency for the MTHFR C677T gene polymorphism was 45.4% and 54.6%, respectively, while the overall A and C allele frequency for the MTHFR A1298C gene polymorphism was 82.3% and 17.6%, respectively. The MTHFR C677T and not the A1298C gene polymorphism had a significantly influence on serum folate and tHcy levels. The individuals with 677TT genotype had significantly lower serum folate and significantly higher serum tHcy levels than individuals with 677 CC or CT genotypes. Serum folate and tHcy levels are influenced by the existence of the MTHFR C677T gene polymorphism (mainly 677TT genotype). Individuals with low serum folate levels and/or high serum tHcy levels should be further investigated for a possible existence of MTHFR C677T and not A1298C gene polymorphisms, with aim to determine the suitable treatment.

The Association between Methylenetetrahydrofolate Reductase (MTHFR) Mutations and Serum Biomarkers of Cardiac Health

Background: Homocysteine (tHcy) has emerged as a new risk factor for cardiovascular diseases (CVD) The Methylenetetrahydrofolate reductase (MTHFR) polymorphisms are seen to give rise to high levels of tHcy which can be a causative factor in the progression of CVD due to its thrombogenic effect. Serum cardiac biomarkers help in the diagnosis, prognosis, or surveillance of CVD. The present study evaluated the association of the two MTHFR mutations, rs1801133 and rs1801131 with 16 well-established serum cardiac markers. Additionally, the influence of age and gender on the association of the two MTHFR polymorphisms with serum cardiac marker levels was also investigated. Methods: The study was carried out on 1295 individuals who visited Vibrant America Clinical Lab for regular or suspected CVD check-ups. The serological markers and genomic variant analysis were carried out as per the standard laboratory protocol under CLIA. The association between serological markers and the rs1801133 and rs1801131 genetic variants with respect to age and gender was evaluated using a one-way ANNOVA test. Results: No significant association was observed in tHcy levels with respect to gender, however, plasma total tHcy levels were higher in males than females. tHcy levels increased with increasing age in the wild and heterozygous genotypes for the mutations, rs1801133 and rs1801131. Additionally, the serum cardiac markers, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Cholesterol (CHOL), Apolipoprotein A (APOA), Apolipoprotein B (APOB), N-terminal (NT)-pro hormone BNP (BNPNT), LDL calculated (LDLCAL), Small Density Low Density Lipoprotein (SDLDL), APOBAR, Oxidised Low Density Lipoprotein (OXLDL), Lipoprotein (A) (LPA), Triglycerides (TRIG), and Lipoprotein-Associated Phospholipase (Lp-PLA2) Test (PLAC) showed significant associations with respect to gender and age for rs1801133 and rs1801131 (P < 0.05) However, these markers were seen to have different trends in correlation with gender and age. Conclusions: The present study reports the association of tHcy, HDL, LDL, CHOL, APOA, APOB, BNPNT, LDLCAL, SDLDL, APOBAR, OXLDL, LPA, TRIG, and PLAC with respect to age and gender for the mutations, rs1801133 and rs1801131. We observed that tHcy levels were high in males and the levels increased with increasing age in males for both polymorphisms. rs1801131 mutant males have high levels of triglyceride whereas rs1801133 mutant postmenopausal females showed high levels of cholesterol. Further analysis will be required to understand the pattern of association of the rest of the serum cardiac markers with age and gender for rs1801133 and rs1801131 mutations.

Acquired Vitamin B12 Deficiency in Newborns: Positive Impact on Newborn Health through Early Detection.

The early diagnosis of and intervention in vitamin B12 deficiency in exclusively breastfed infants by mothers with low vitamin B12 is crucial in preventing possible irreversible neurologic damage, megaloblastic anemia, and failure to thrive. We assess the usefulness of the early detection of asymptomatic B12 deficiency related to acquired conditions and highlight the importance of monitoring serum vitamin B12 levels during pregnancy. We describe demographic, clinical, dietary, and biochemical data, including the evolution of a vitamin B12 deficiency’s functional biomarkers. We enrolled 12 newborns (5 males) with an age range of 1–2 months old that were exclusively breastfed and asymptomatic. These cases were referred to our metabolic unit due to alterations in expanded newborn screening: high levels of methylmalonic acid and/or total homocysteine (tHcy). All mothers were under a vegetarian diet except three who had abnormal B12 absorption, and all presented low or borderline serum B12 level and high plasma levels of tHcy. Supplementation with oral vitB12 re-established the metabolic homeostasis of the mothers. In infants, therapy with an intramuscular injection of 1.0 mg hydroxocobalamin led to the rapid normalization of the metabolic pattern, and a healthy outcome was observed. Acquired B12 deficiency should be ruled out before proceeding in a differential diagnosis of cobalamin metabolism deficits, methylmalonic acidemia, and homocystinuria.

Individual and joint effects of borderline ankle-brachial index and high plasma total homocysteine on all-cause death in hypertensive adults.

BACKGROUNDThe cardiovascular hazards of total homocysteine (tHcy) are long known. In addition, despite the acknowledgment on the importance of low ankle-brachial index (ABI) (< 0.9), borderline ABI (0.91-0.99) was once commonly overlooked. This study aims to explore the independent and joint effect of tHcy level and borderline ABI on all-cause death in hypertensive population.METHODSThis study included 10,538 participants from China H-type Hypertension Registry Study. ABI was described into two groups: normal ABI (1.00-1.40) and borderline ABI. tHcy level was also divided into two groups: < 15.02 and ≥ 15.02 μmo/L. Four groups were analyzed, using COX proportional hazard regression model, separately and pairwise to observe the independent and joint effect on all-cause death.RESULTSA total of 126 (1.2%) deaths were observed in the 1.7 years follow-up time. Borderline ABI has a higher predicted risk of death than normal ABI (HR = 1.87, 95%CI: 1.17-3.00) after adjusting for potential covariates. Compare with tHcy level < 15.02 μmo/L (low tHcy), those with tHcy ≥ 15.02 μmo/L (high tHcy) had higher risk to event outcome (HR = 1.99, 95% CI: 1.30-3.05). According to the cumulative hazard curve, group with borderline ABI and high tHcy level has significantly higher altitude and larger increasing rate over follow-up period compare to other groups. Among those with borderline ABI, participants with high tHcy had higher death risk than those with low tHcy, nevertheless, no significant different between borderline and normal ABI among those with low tHcy levels.CONCLUSIONSBorderline ABI and tHcy level both have independent predictive value on all-cause death. The combined group of borderline ABI and high tHcy has highest risk factor of outcomes, which suggested the mutual additive value of borderline ABI and tHcy. More attention should be given to the importance of borderline ABI in hypertensive population, especially with elevated tHcy level.

Combined homocysteine and apoE rs429358 and rs7412 polymorphism in association with serum lipid levels and cognition in Chinese community-dwelling older adults

BackgroundApoE gene polymorphism and serum total homocysteine (tHcy) has been reportedly associated with cognition. In this study, we assessed the association of combined ApoE gene polymorphism and tHcy with cognition in Chinese elder adults.MethodsA cross- sectional study was carried out by recruiting 1458 community-dwelling people aged 55+ and above in Beijing in 2009. All participants were interviewed using a standard questionnaire and underwent a physical examination. The mini-mental scale examination (MMSE) score was used in assessing cognitive function. Fasting venous blood samples were taken for ApoE rs429358, rs7412 genotyping, tHcy and other serum lipid measurements.ResultsParticipants with high serum tHcy level showed a relatively lower orientation, attention abilities as well as the total MMSE score than the group with normal tHcy after adjusting confounding factors. ApoE rs429358 and rs7412 variants were observed to have the highest serum TC and TG level in the subjects with high serum tHcy level (p < 0.05). Cognition of the subjects was found to be significantly associated with high serum tHcy level and ApoE genetic polymorphism (p < 0.05). Independent of age, BMI, education levels, smoking and alcohol drinking, the worst cognitive ability were detected in the high serum tHcy level subjects with ApoE rs429358C/T and rs7412 C/T as compare with other groups, especially orientation function, memory and delayed recall ability and attention ability.ConclusionHigh serum tHcy level in combination with ApoE rs429358 and rs7412 variants might be linked with serum lipid levels and cognition, particularly for orientation function and memory and delayed recall ability in old Chinese adults.

A Descriptive Study of Total Serum Homocysteine Status in Adult Henan Province, China.

Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease. Total serum homocysteine (tHcy) status varies greatly with ethnicity and gender. Here, we studied the tHcy status by investigating concentration of tHcy and calculating prevalence of HHcy according to different age groups and genders. This is a cross-sectional study of 10,258 participants (7,248 males and 3,010 females) above 19 years old from Henan Province, northern China. tHcy levels were determined enzymatically. HHcy was defined as a tHcy level higher than 15 μmol/L. In the whole population, the median value of tHcy was 13.56 (11.50, 16.50) μmol/L, and the HHcy prevalence was 34.61%. Males had much higher tHcy levels than females: 14.51 (12.58, 17.71) μmol/L vs. 11.23 (9.75, 12.97) μmol/L, p < 0.001. Also, males had much higher HHcy prevalence than females (44.33% vs. 11.20%, p < 0.001, OR = 6.33, 95% CI: 5.59 - 7.14). HHcy prevalence and tHcy levels increased greatly for both genders above 60 years old. Our results demonstrated that prevalence of HHcy is very high in northern China. Implementation of tHcy-lowering strategies is needed.

Periconceptional maternal and paternal homocysteine levels and early utero-placental (vascular) growth trajectories: The Rotterdam periconception cohort.

Maternal elevated plasma total homocysteine (tHcy) is involved in the origin of several placenta-related pregnancy complications. The first trimester is the most sensitive period for placentation influenced by maternal and paternal health. The aim is to study associations between periconceptional parental tHcy levels and utero-placental growth trajectories in the first trimester of pregnancy. Pregnant women and their partners were enrolled before 10 weeks of gestation in the Virtual Placenta study as subcohort of the Rotterdam periconception cohort (Predict study). A total of 190 women with a singleton pregnancy, of which 109 conceived naturally and 81 after IVF/ICSI treatment, were included. We measured serial utero-placental vascular volumes (uPVV) and placental volumes (PV) at 7, 9 and 11 weeks of gestation. First-trimester trajectories of PV were also measured in 662 pregnancies from the total Predict study. Comparing all participants of the virtual placenta study, no association between maternal tHcy and uPVV was observed. However, in IVF/ICSI pregnancies sub-analyses showed significantly negative associations between maternal tHcy in the 3rd and 4th quartile and uPVV trajectories (beta: -0.38 (95%CI -0.74 to -0.02) and beta: -0.42 (95% CI -0.78 to -0.05), respectively) with the 1st quartile as reference. Analysis in the total Predict cohort showed similar negative associations for the total study population. Periconceptional high maternal tHcy levels are associated with smaller placental growth trajectories depicted as PV and uPVV in the first trimester of pregnancy. The stronger negative associations with uPVV in IVF/ICSI pregnancies underline the need for further investigation.

Total Plasma Homocysteine and Depressive Symptoms in Older Hispanics.

Very few studies have investigated the association between total plasma homocysteine (tHcy) and depressive symptoms in older Hispanics. To test the hypothesis that high tHcy associates with depressive symptoms in older Hispanics. A total of 1,418 participants .55 years old from the Maracaibo Aging Study (MAS) underwent standardized neurological, neuropsychiatric, and cardiovascular assessments. The Neuropsychiatric Inventory Depression Subscale (NPId) was used to assess the burden of depressive symptoms. The tHcy levels and other biochemical parameters in blood samples were measured. Univariate and multivariate logistic regression models were applied. Participants with depressive symptoms had higher levels of tHcy than those without (15.1 versus 13.9 µmol/L; p = 0.009). Elevated tHcy levels were associated with depressive symptoms after adjusting for age, sex, education, smoking, diabetes, hypertension, alcohol intake, stroke, and dementia (OR = 1.58; 95% CI, 1.18-2.12). Elevated levels of tHcy were associated with depressive symptoms in older Hispanics living under the nutritional and environmental conditions of a developing country.

Association Between Plasma Total Homocysteine Levels and Risk of Early Hemorrhagic Transformation in Patients with Acute Ischemic Stroke: A Hospital-Based Study

ObjectsIn this study, we investigated the association between plasma total homocysteine(tHcy) levels and the risk of early hemorrhagic transformation(HT) in patients with acute ischemic stroke(AIS). MethodsConsecutive hospitalized participants who met the inclusion criteria were enrolled and grouped according to plasma tHcy levels. Participants were divided into a low homocysteine level(L-tHcy) group (<12 µmol/L) and a high homocysteine level group(H-tHcy) (≥ 12 µmol/L). Baseline computed tomography (CT) examination was performed. HT was determined via CT or magnetic resonance imaging within 1 to 3 days after admission. ResultsA total of 1858 patients were screened and 1378 patients completed the this study(797 patients in the H-tHcy group and 581 patients in the L-tHcy group). HT incidence was 5.2% (30/581,) in the L-tHcy group and 11.2% (90/797) in the H-tHcy group(P<0.05). Binary logistic regression analysis showed that initial NIHSS score, tHcy levels, treatment with recombinant tissue plasminogen activator thrombolysis, systolic blood pressure on admission, glucose level on admission, smoking status and estimated glomerular filtration rate were independent risk factors for HT. Receiver operating characteristic analysis showed that tHcy level was a moderately sensitive and specific index to predict the incidence of HT, and the optimal cutoff was 16.56 μmol/L (sensitivity 63.3%, specificity 41.3%). ConclusionOur study findings reveal that high plasma tHcy level is one independent risk factor associated with increased risk of early HT in patients with AIS.

Elevated Total Homocysteine Predicts In-Hospital Pneumonia and Poor Functional Outcomes in Acute Ischemic Stroke.

We investigated the association between elevated total homocysteine (tHcy) levels upon hospital admission and short-term in-hospital outcomes, including pneumonia in acute ischemic stroke (AIS) patients. A total of 2,084 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included in the present study. We divided patients into four groups according to their level of admission tHcy: quartile (Q1) (<9.70 umol/L), Q2 (9.70-12.3 umol/L), Q3 (12.3-16.9 umol/L), and Q4 (≥16.9 umol/L). Logistic regression models were used to estimate the effect of tHcy on the short-term outcomes, including in-hospital pneumonia, all-cause in-hospital mortality, and poor outcome upon discharge (modified Rankin Scale score ≥3) in AIS patients. The risk of in-hospital pneumonia was significantly higher in patients with the highest tHcy level (Q4) compared to those with the lowest tHcy level (Q1) (adjusted odds ratio [OR] 1.55; 95% confidence interval [CI], 1.03-2.33; P-trend =0.019). The highest tHcy level (Q4) was associated with a 3.35-fold and 1.50-fold increase in the risk of in-hospital mortality (OR 3.35; 95% CI, 1.11-10.13; P-trend =0.015) and poor outcome upon discharge (OR 1.50; 95% CI, 1.06-2.12; Ptrend =0.044) in comparison to Q1 after adjustment for potential covariates including pneumonia. Having a high admission tHcy level was independently associated with in-hospital pneumonia, in-hospital mortality, and poor outcome upon discharge in AIS patients.

Association of Homocysteine, Methionine, and MTHFR 677C>T Polymorphism With Rate of Cardiovascular Multimorbidity Development in Older Adults in Sweden

Strong evidence links high total serum homocysteine (tHcy) and low methionine (Met) levels with higher risk of ischemic disease, but other cardiovascular (CV) diseases may also be associated with their pleiotropic effects. To investigate the association of serum concentrations of tHcy and Met with the rate of CV multimorbidity development in older adults and to explore the role of methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism in this association. The Swedish National Study on Aging and Care in Kungsholmen is a cohort study of randomly selected individuals aged 60 years or older. The present study included data on 1969 individuals with complete information and without CV diseases at baseline, collected from the baseline examination (2001-2004) to the fourth follow-up (2013-2016). Data analysis was conducted from January to May 2019. Concentrations of tHcy and Met were measured from nonfasting venous blood samples. The Met:tHcy ratio was considered a possible indicator of methylation activity. MTHFR status was dichotomized as any T carriers vs noncarriers. The number of CV diseases at each wave was ascertained based on medical interviews and records, laboratory test results, and drug data. Linear mixed models were used to study the association of baseline tHcy and Met levels and the rate of CV multimorbidity development, adjusting for sociodemographic characteristics, CV risk factors, chronic disease burden, and drug use. Of 1969 participants, most were women (1261 [64.0%]), with a mean (SD) age of 70.9 (9.8) years; 1703 participants (86.6%) had at least a high school level of education. Baseline measurements of serum tHcy, Met, and the Met:tHcy ratio were associated with the rate of CV disease accumulation (tHcy: β = 0.023 per year; 95% CI, 0.015 to 0.030; P < .001; Met: β = -0.007 per year; 95% CI, -0.013 to -0.001; P = .02; Met:tHcy ratio: β = -0.017 per year; 95% CI, -0.023 to -0.011; P < .001). The association between low Met concentrations and the rate of CV multimorbidity development was restricted to the group with CT/TT alleles of MTHFR (β = 0.023 per year; 95% CI, 0.006 to 0.041; P = .009). Results remained largely significant when individual CV diseases were removed from the total count 1 at a time (eg, ischemic heart disease, tHcy: β = 0.023 per year; 95% CI, 0.013 to 0.027; P < .001; Met: β = -0.006 per year; 95% CI, -0.011 to -0.0003; P = .04; Met:tHcy ratio: β = -0.015 per year; 95% CI, -0.020 to -0.009; P < .001). In this study, high tHcy and low Met levels were associated with faster CV multimorbidity development in older age. The interactive association of Met concentrations and MTHFR polymorphism, together with the association found for the Met:tHcy ratio, point toward the relevance of impaired methylation in the pathogenesis of CV aging.

Associations between B vitamin and amino acid intake, MTHFR genotype, atherogenic indices, and homocysteine levels in postmenopausal women

AbstractIt has been hypothesized that insufficiency of one-carbon metabolism may aggravate lipid metabolism disturbances. Lipid metabolism abnormalities and metabolic syndrome (MetS)—which is associated with abnormally high levels of triglycerides (TG) and low levels of high-density lipoproteins (HDL)—often occur in postmenopausal women. The purpose of this study was thus to determine the relationships between amino acid and B vitamin intake, MTHFR genotype, lipid profile, and atherogenic indices in postmenopausal women.131 postmenopausal women were enrolled for the study. The mean macronutrient, amino acid, and B vitamin intake was evaluated using dietary records. Lipid profile and concentrations of apolipoprotein A1 (ApoA1) and B (ApoB) in serum were measured using the colorimetric method. The total homocysteine (tHcy) and glutathione (GSH) level in plasma were measured using high-performance liquid chromatography. MTHFR genotype (rs1801133) was determined using a single tube TaqMan SNP Genotyping Assay. We calculated atherogenic indices, such as Castelli's risk index I and II (CRI-I and CRI-II), the atherogenic coefficient (AC), and the TG/HDL ratio.No association was found between MetS and tHcy or GSH concentrations. MTHFR genotype and folate intake also did not affect tHcy, GSH, lipid profile, or atherogenic indices. Subjects with tHcy levels over the median had lower total protein intake, lower animal protein/plant protein ratio, lower protein/carbohydrates ratio, and higher amino acid intake (methionine, lysine, arginine, glycine, and tryptophan) than did subjects with lower tHcy levels. Women who failed to meet their vitamin B12 intake needs had almost 40% higher levels of tHcy than women who did met those needs.MTHFR genotype, folate intake, and tHcy levels in plasma are not associated with lipid metabolism in postmenopausal women. tHcy levels may depend on the intake of vitamin B12, and of protein or particular amino acids.The project was financed by the National Science Centre, Poland (grant number 2015/17/N/NZ9/04133).

Measurement of melatonin, indole-dioxygenase, IL-6, IL-18, ferritin, CRP, and total homocysteine levels during herpes zoster.

The risk of herpes zoster (HZ) increases with age and declining immune function. Increased oxidative stress and inflammatory conditions may cause a negative impact on the immune responses. The present study aimed to assess the levels of oxidative/inflammatory stress biomarkers in HZ patients compared with the controls. This case-control study included 43 HZ patients and 47 age-matched controls. Melatonin (MLT), Indole-dioxygenase (IDO), Interleukin-18 (IL-18), Interleukin-6 (IL-6), ferritin, C-reactive protein (hsCRP), and total homocysteine (tHcy) levels were measured and compared in both groups. The significant high levels of IDO, IL-18, IL-6, ferritin, hsCRP, and tHcy, as well as low levels of MLT were found in HZ patients compared with the controls (P < 0.001); these significant differences were also associated with rash and pain severity (P < 0.001). The final logistic regression model with the area under the curve (0.99; 95% confidence interval [CI], 0.98-1.00) showed the association of HZ with decreased level of MLT (odds ratio [OR], 0.95; 95% CI, 0.92-0.98; P = 0.007) and increased levels of tHcy (OR, 1.53; 95% CI, 1.06-2.19; P = 0.02). The findings showed increased inflammation-associated oxidative stress in HZ patients. Elevated tHcy levels and reduced MLT levels may be associated with the manifestation of HZ. More investigations are required to confirm the results.

Association Between Homocysteine Level and Methylenetetrahydrofolate Reductase Gene Polymorphisms in Type 2 Diabetes Accompanied by Dyslipidemia.

Objective To investigate the association between total homocysteine (tHcy) level in plasma and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus (T2DM) accompanied by dyslipidemia. Methods This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively. Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of MTHFR C677T and A1298C. Plasma tHcy and lipid levels were measured as well. The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using Chi-square test. Plasma tHcy level of T2DM patients who carried the different genotypes was compared by Student's t test. Results Finally, 82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study. There was a significant correlation between tHcy level and MTHFR C677T gene polymorphism in T2DM patients (t=2.27, P=0.02). Moreover, the plasma tHcy level in the dyslipidemia patients who carried MTHFR 677 TT genotype was significantly higher than that in those with CT+CC genotype (13.62±6.97 vs. 10.95±3.62 μmol/L, t=2.20, P=0.03); while for patients without dyslipidemia, comparison of the tHcy level between those who carried the above two alleles showed no significantly difference (13.34±6.03 vs. 12.04±5.09 μmol/L, t=1.08, P=0.29). Conclusion MTHFR 677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.