Serum interleukin-17 A and homocysteine levels in children with autism.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that typically emerges early in childhood. This study aimed to explore the potential link between serum levels of vitamin B12 and homocysteine (Hcy) and the severity of ASD symptoms in children. METHODS: In this study, 50 children diagnosed with ASD comprised the observation group, while 50 healthy children constituted the control group. Serum levels of IL-17 A, Hcy, folate, and vitamin B12 were compared between the study group and control group, as well as among children with different degrees of ASD severity. The correlation between the Childhood Autism Rating Scale (CARS) score and serum levels of IL-17 A, Hcy, folate, and vitamin B12 was examined. Additionally, the relationship between serum IL-17 A and Hcy levels and their association with the severity ASD were explored. RESULTS: Compared to the control group, the observation group demonstrated elevated serum Hcy and IL-17 A levels alongside decreased folate and vitamin B12 levels. Individuals with severe ASD exhibited higher Hcy and IL-17 A levels but lower folate and vitamin B12 levels compared to those with mild to moderate ASD. The CARS score showed negative correlations with serum folate and vitamin B12 levels and positive correlations with serum IL-17 A and Hcy levels in ASD patients. Additionally, serum Hcy and IL-17 A levels were correlated with ASD severity. CONCLUSION: Children diagnosed with ASD presented with reduced serum vitamin B12 levels and increased levels of Hcy, potentially contributing to the onset and severity of ASD.

Relationship between Serum Homocysteine Concentration and Dietary Factors in Young Japanese Women.

Homocysteine is a methionine metabolism intermediate and its increased blood levels are associated with a higher risk of noncommunicable diseases. Reportedly, blood homocysteine levels increase with inadequate folate, vitamin B6, and vitamin B12 intake; however, its relationship with dietary factors other than these three vitamins remains unknown. Thus, we investigated the relationship of homocysteine with other nutrient intake. We performed a dietary survey on 227 young women using a food record with approximate amounts for 7 consecutive days in conjunction with digital imaging. We collected early morning fasting blood samples the day after the dietary survey was completed and analyzed the serum homocysteine levels. We observed that the serum homocysteine concentrations were significantly negatively associated with soluble, insoluble, and total fiber intake. In addition, participants with high fruit and mushroom intake displayed lower serum homocysteine concentrations, suggesting dietary fiber involvement from these foods. However, we observed no serum homocysteine concentration-related association with cereals and vegetables (well-documented dietary fiber sources) or with fruits and mushrooms. In conclusion, fiber quality-related differences could thus be caused by different sources, including antioxidant components such as fruit polyphenols and mushroom antioxidant and anti-inflammatory factors.

The association between circulating Hcy and Lp-PLA2 levels and poststroke depression: A meta-analysis.

OBJECTIVE: To analyze the correlation between circulating homocysteine (Hcy) and lipoprotein-associated phospholipase A2 (Lp-PLA2) levels and poststroke depression (PSD). MATERIALS AND METHODS: Chinese (Chinese National Knowledge Infrastructure, Wanfang, and VIP) and English (PubMed, EMBASE, MEDLINE, and Cochrane Library) databases on the correlation between circulating Hcy and Lp-PLA2 and PSD were collected. Meta-analysis was performed to compare the distinctions in circulating Hcy and Lp-PLA2 levels between PSD and non-PSD groups. Meta-analysis was conducted by using STATA 15.0 software. RESULTS: A total of 20 literatures were included in this study. The level of circulating Lp-PLA2 in the PSD group was obviously higher than that in the non-PSD group (weighted mean differences: 2.75, 95%CI: 0.10-5.39, P = .002), which was an independent predictor of PSD (effect size = 0.05, 95%CI: 0.03, 0.07, P < .001). The level of circulating Hcy in the PSD group was obviously higher than that in the non-PSD group (weighted mean differences = 1.41, 95%CI: 1.01, 1.81, P < .001), which was an independent influencing factor for the occurrence of PSD (effect size = 0.07, 95%CI: 0.04, 0.09, P = .011). CONCLUSION: Circulating Hcy and Lp-PLA2 levels are linked to the development of PSD, and can be applied as predictive or diagnostic indicators.

[Association between maternal plasma one-carbon biomarkers during pregnancy and fetal growth in twin pregnancies].

Objective: To characterize the relationship between the levels of plasma methyl donor and related metabolites (including choline, betaine, methionine, dimethylglycine and homocysteine) and fetal growth in twin pregnancies. Methods: A hospital-based cohort study was used to collect clinical data of 92 pregnant women with twin pregnancies and their fetuses who were admitted to Peking University Third Hospital from March 2017 to January 2018. Fasting blood was collected from the pregnant women with twin pregnancies (median gestational age: 18.9 weeks). The levels of methyl donors and related metabolites in plasma were quantitatively analyzed by high-performance liquid chromatography combined with mass spectrometry. The generalized estimation equation was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and neonatal outcomes of twins, and the generalized additive mixed model was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and fetal growth ultrasound indicators. Results: (1) General clinical data: of the 92 women with twin pregnancies, 66 cases (72%) were dichorionic diamniotic (DCDA) twin pregnancies, and 26 cases (28%) were monochorionic diamniotic (MCDA) twin pregnancies. The comparison of the levels of five plasma methyl donors and related metabolites in twin pregnancies with different basic characteristics showed that the median levels of plasma choline and betaine in pregnant women ≥35 years old were higher than those in pregnant women <35 years old, and the differences were statistically significant (all P<0.05). (2) Correlation between plasma methyl donor and related metabolites levels and neonatal growth indicators: after adjusting for confounding factors, plasma homocysteine level in pregnant women with twins was significantly negatively correlated with neonatal birth weight (ß=-47.9, 95%CI:-94.3- -1.6; P=0.043). Elevated methionine level was significantly associated with decreased risks of small for gestational age infants (SGA; OR=0.5, 95%CI: 0.3-0.9; P=0.021) and low birth weight infants (OR=0.6, 95%CI: 0.4-0.9; P=0.020). Increased homocysteine level was associated with increased risks of SGA (OR=1.5, 95%CI: 1.0-2.2; P=0.029) and inconsistent growth in twin fetuses (OR=1.9, 95%CI: 1.0-3.7; P=0.049). (3) Correlation between the levels of plasma methyl donors and related metabolites and intrauterine growth indicators of twins pregnancies: for every 1 standard deviation increase in plasma choline level in pregnant women with twin pregnancies, fetal head circumference, abdominal circumference, femoral length and estimated fetal weight in the second trimester increased by 1.9 mm, 2.6 mm, 0.5 mm and 20.1 g, respectively, and biparietal diameter, abdominal circumference and estimated fetal weight increased by 0.7 mm, 3.0 mm and 38.4 g in the third trimester, respectively, and the differences were statistically significant (all P<0.05). (4) Relationship between plasma methyl donor and related metabolites levels in pregnant women with different chorionicity and neonatal birth weight and length: the negative correlation between plasma homocysteine level and neonatal birth weight was mainly found in DCDA twin pregnancy (ß=-65.9, 95%CI:-110.6- -21.1; P=0.004). The levels of choline, betaine and dimethylglycine in plasma of MCDA twin pregnancy were significantly correlated with the birth weight and length of newborns (all P<0.05). Conclusion: Homocysteine level is associated with low birth weight in twins, methionine is associated with decreased risk of SGA, and choline is associated with fetal growth in the second and third trimesters of pregnancy.

Association of Prolactin, Oxytocin, and Homocysteine With the Clinical and Cognitive Features of a First Episode of Psychosis Over a 1-Year Follow-Up.

BACKGROUND: The clinical debut of schizophrenia is frequently a first episode of psychosis (FEP). As such, there is considerable interest in identifying associations between biological markers and clinical or cognitive characteristics that help predict the progression and outcome of FEP patients. Previous studies showed that high prolactin, low oxytocin, and high homocysteine are factors associated with FEP 6 months after diagnosis, at which point plasma levels were correlated with some clinical and cognitive characteristics. METHODS: We reexamined 75 patients at 12 months after diagnosis to measure the evolution of these molecules and assess their association with clinical features. RESULTS: At follow-up, FEP patients had lower prolactin levels than at baseline, and patients treated with risperidone or paliperidone had higher prolactin levels than patients who received other antipsychotic agents. By contrast, no changes in oxytocin and homocysteine plasma levels were observed between the baseline and follow-up. In terms of clinical features, we found that plasma prolactin and homocysteine levels were correlated with the severity of the psychotic symptoms in male FEP patients, suggesting that they might be factors associated with psychotic symptomatology but only in men. Together with oxytocin, these molecules may also be related to sustained attention, verbal ability, and working memory cognitive domains in FEP patients. CONCLUSION: This study suggests that focusing on prolactin, oxytocin, and homocysteine at a FEP may help select adequate pharmacological treatments and develop new tools to improve the outcome of these patients, where sex should also be borne in mind.

Additive effect between homocysteine and low-density-lipoprotein cholesterol upon incidence of novel carotid plaque formation: data from a Chinese community-based cohort.

OBJECTIVE: Homocysteine (HCY) has been associated with carotid plaque in cross-sectional studies, but the prospective relationship between HCY and incident carotid plaque has not been well established. The purpose of this study was to investigate the association between HCY and incidence of novel carotid plaque in a Chinese community-based population without pre-existing carotid atherosclerosis and to assess the additive effect of HCY and low-density lipoprotein cholesterol (LDL-C) on the incidence of novel plaque. METHODS: At baseline, we measured HCY and other risk factors in subjects aged ≥ 40 years. All participants underwent carotid ultrasound examinations at baseline and after an average of 6.8 years of follow-up. Incidence of plaque was identified if plaque was absent at baseline, but plaque was detected at the end of follow-up. A total of 474 subjects were included in the analysis. RESULTS: The incidence of novel carotid plaque was 24.47%. Multivariate regression analyses showed that HCY was independently associated with a 1.05-fold-higher likelihood for incident novel plaque (adjusted odds ratio [OR] = 1.05, 95% confidence interval [CI]: 1.01-1.09, P = 0.008). Using tertile 1 and tertile 2 for reference, the top HCY tertile (T3) showed a 2.28-fold-higher likelihood for incident plaque (adjusted OR = 2.28, 95%CI: 1.33-3.93, P = 0.002). The combination of HCY T3 and LDL-C ≥ 3.4 mmol/L had the highest risk for novel plaque formation (adjusted OR = 3.63, 95%CI: 1.67-7.85, P = 0.001) compared to those without either condition. In the LDL-C ≥ 3.4 mmol/L subgroup, HCY was significantly associated with incidence of plaque (adjusted OR = 1.16, 95%CI: 1.04-1.28, P = 0.005, P-interaction = 0.023). CONCLUSION: In the Chinese community-based population, HCY was independently associated with the incidence of novel carotid plaque. There were additive effect between HCY and LDL-C on the incidence of plaque, the highest risk was observed in individuals with both high HCY levels and LDL-C ≥ 3.4 mmol/L. Our findings suggest that HCY may be a potential target for preventing the incidence of carotid plaque, particularly in individuals with elevated LDL-C levels.

Homocysteine serum levels correlate with the number of failed IVF cycles even when within normal range.

INTRODUCTION: Repeated implantation failure is a common challenge in daily practice. Homocysteine and vitamin B12 have been associated with reproductive processes among patients undergoing in vitro fertilization; however, their involvement in repeated implantation failure has not been assessed. We explored possible associations of serum homocysteine and vitamin B12 with repeated implantation failure. MATERIAL AND METHODS: A retrospective analysis of 127 women who underwent ≥ 3 unsuccessful embryo transfers during 2005-2016, at the Fertility and In Vitro Fertilization Unit at Carmel Medical Center. After at least 3 IVF failures serum levels of homocysteine and vitamin B12 were measured. RESULTS: The mean patient age was 33.5 ± 5.2 years. The mean number of embryo transfers was 4.6 ± 1.5. The mean total cumulative number of embryos transferred was 10.4 ± 5.2. Mean serum levels of homocysteine were 8.6 ± 3.7 µM/L, and of vitamin B12 were 302.5 ± 155.3 pg/ml. Homocysteine levels were within the normal range (< 14 µM/L) in 95.8% of the patients. Yet, the levels of homocysteine correlated with both the number of failed embryo transfers (r = 0.34, p = 0.004) and the total cumulative number of transferred embryos (r = 0.36, p = 0.002). CONCLUSIONS: Our findings suggest an association between serum homocysteine levels and the occurrence of repeated implantation failure, even when homocystein levels were within the normal range. It should be studied whether nutritional supplementation to modulate serum homocysteine levels may improve treatment outcome.

Homocysteine Levels in Severe OSA Patients Before and After TORS-OSA Surgery.

OBJECTIVE: The increased risk of cardiovascular diseases owing to a high level of serum homocysteine has been widely reported. Literature has demonstrated that patients with obstructive sleep apnea/hypopnea syndrome (OSA) had a higher homocysteine level than control group. This study aimed to investigate the alteration of serum homocysteine levels in severe OSA patients receiving transoral robotic surgery (TORS). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic medical center. METHODS: Data of polysomnography (PSG) and serum homocysteine levels before and at least 3 months after the surgery were collected and analyzed via paired t tests. A subgroup analysis based on the preoperative homocysteine level (≥15 mcmol/L, as hyperhomocysteinemia group) was conducted to compare the intergroup differences of homocysteine decrease. Pearson's correlation was used to survey the relationships between the changes of major PSG parameters and the levels of homocysteine decrease at baseline and after TORS-OSA surgery. RESULTS: Two hundred sixty-one patients with severe OSA were enrolled. There were significant improvements in major PSG parameters after TORS-OSA surgery. Homocysteine levels significantly decreased from 12.1 ± 3.9 to 11.4 ± 3.7 mcmol/L (difference = -0.7 ± 2.8 mcmol/L, p = .001) postoperatively, which was shown in the hyperhomocysteinemia group (difference = -2.9 ± 4.7 mcmol/L, p = .007) to a greater extent. Pearson's correlation revealed that ΔODI (oxygen desaturation index/h) was the predominant estimate with a positive association with Δhomocysteine (r = 0.525, p = .012). CONCLUSION: TORS-OSA surgery could decrease homocysteine levels in OSA patients. The effects were more relevant in severe OSA patients with abnormal preoperative homocysteine levels.

Homocysteine concentrations in overweight children and adolescents.

OBJECTIVE: The aim of this study was to describe homocysteine concentrations in overweight and obese children and adolescents and relate them to blood pressure levels, renal function, and insulin resistance. METHODS: This is a cross-sectional and observational study with 64 overweight children and adolescents (mean age: 11.6±3.5 years) in outpatient follow-up. The following parameters were evaluated: body mass index z-score, waist-to-height circumference ratio, pubertal stage, blood pressure, serum homocysteine, glycemia, insulin, lipid profile, renal function, high-sensitivity C-reactive protein, microalbuminuria, and creatinuria. Statistical analysis: analysis of variance and logistic regression (dependent variable: homocysteine) (p<0.05). RESULTS: The mean body mass index z-score was 2.9±1.1. The mean homocysteine concentrations were 8.6±2.2 µmol/L (10th and 90th percentiles: 6.6 and 11.2 µmol/L, respectively), with no difference when compared with children with severe obesity and obesity/overweight (p=0.431). High values of waist-to-height ratio (93.8%), systolic blood pressure (18.8%), diastolic blood pressure (12.5%), glycemia (4.7%), low-density lipoprotein cholesterol (31.1%), triglycerides (35.9%), non-high-density lipoprotein cholesterol (34.4%), and microalbuminuria (21.9%) were obtained. The mean glomerular filtration rate was 122.9±24.6 mL/min/1.73 m². Homocysteine concentrations were not associated with any of the studied variables (R²=0.095). CONCLUSION: Homocysteine concentrations in overweight children and adolescents (mean 8.6±2.2 µmol/L) were not associated with body mass index z-score, blood pressure, renal function, and insulin resistance.

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.

Poly(N-2-hydroxypropylmethacrylamide)-capped gold nanoparticles as nanozymes with peroxidase-mimicking performance for the colorimetric monitoring of serum homocysteine.

Recently, nanozymes based on polymer-stabilized gold nanoparticles (AuNPs) have attracted more and more attention on account of their polymer-ligands' multiple functionalization sites. However, the contribution of polymer hydrogen bonding to the catalytic activity of AuNPs has received little attention. This study designed and fabricated poly(N-2-hydroxypropylmethacrylamide)-capped AuNPs (PHPAM@AuNPs) using a hydroxyl-rich polymer as the ligand. The PHPAM@AuNPs exhibited good peroxidase-mimicking activity capable of efficiently oxidizing 3,3'5,5'-tetramethylbenzidine (TMB) with H2O2. The effect of PHPAM hydrogen bonding on the catalytic activity of PHPAM@AuNPs was investigated. Under peroxidase-mimicking catalysis, homocysteine introduced a notable reduction in oxidation, allowing the creation of a colorimetric method for homocysteine detection with high selectivity and sensitivity. The ultraviolet-visible absorption intensity of oxidized TMB showed a strong linear relationship with homocysteine concentration in the range of 3.0-20.0 µM (R2 = 0.998), with a limit of detection of 0.4 µM. The proposed colorimetric protocol was used to monitor homocysteine in rat serum following intraperitoneal injection. This work provides a new way to refine AuNP-based nanozymes by relying on polymer-ligand hydrogen bonding. It has strong application potential in the analysis of endogenous molecules in real samples.

Relevance of Plasma Homocysteine and Methylenetetrahydrofolate Reductase 677TT Genotype in Sickle Cell Disease: A Systematic Review and Meta-Analysis.

We evaluated the relevance of plasma homocysteine (HC) and the TT genotype of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) in sickle cell disease (SCD) and associated vaso-occlusive crisis (VOC) and ischemic stroke (IS). We identified in Embase and Medline 22 studies on plasma HC and 22 on MTHFR genotypes. Due to age-related HC differences, adult and paediatric SCD were separated: 879 adult SCD and 834 controls (CTR) yielded a neutral effect size; 427 paediatric SCD and 625 CTR favoured SCD (p = 0.001) with wide heterogeneity (I2 = 95.5%) and were sub-grouped by country: six studies (Dutch Antilles n = 1, USA n = 5) yielded a neutral effect size, four (India n = 1, Arab countries n = 3) favoured SCD (p < 0.0001). Moreover, 249 SCD in VOC and 419 out of VOC yielded a neutral effect size. The pooled prevalence of the MTHFR TT genotype in 267 SCD equalled that of 1199 CTR (4.26% vs. 2.86%, p = 0.45), and in 84 SCD with IS equalled that of 86 without IS (5.9% vs. 3.7%, p = 0.47); removal of one paediatric study yielded a significant effect size (p = 0.006). Plasma HC in paediatric SCD from Middle East and India was higher, possibly due to vitamin deficiencies. Despite its low prevalence in SCD, the MTHFR TT genotype relates to adult IS.

Different effects of maternal homocysteine concentration, MTHFR and MTRR genetic polymorphisms on the occurrence of fetal aneuploidy.

RESEARCH QUESTION: Do maternal homocysteine (Hcy) concentrations, MTHFR and MTRR genes have effects on the occurrence of fetal aneuploidy? DESIGN: A total of 619 aneuploidy mothers and 192 control mothers were recruited in this study. Differences in distributions of maternal MTHFR 677C>T, MTHFR 1298A>C and MTRR 66A>G genetic polymorphisms and maternal Hcy concentrations between aneuploidy mothers and control mothers were analysed. RESULTS: The maternal MTHFR 677C>T polymorphism was found to be a risk factor for the occurrence of many fetal non-mosaic aneuploidies studied here, including trisomies 13, 15, 16, 18, 21, 22, TRA and TS. The maternal MTHFR 1298A>C polymorphism was found to be a risk factor specifically associated with the occurrence of fetal trisomy 15 and fetal TS. The maternal MTRR 66A>G polymorphism was found to be a risk factor only specifically associated with the occurrence of fetal trisomy 21. The Hcy concentrations of mothers of trisomies 22, 21, 18, 16, 15 and TS fetuses were significantly higher than the Hcy concentrations of control mothers. CONCLUSIONS: Overall, data suggested an association between these maternal polymorphisms and the susceptibility of fetal non-mosaic trisomy and Turner syndrome. However, these three maternal polymorphisms had different associations with the susceptibility of different fetal aneuploidies, and the elevated maternal Hcy concentration appeared to be a likely risk factor for fetal Turner syndrome and fetal trisomies.

Homocysteine and the Mortality of Critically Ill Patients: A Meta-Analysis.

Prevalence of hyperhomocysteinemia (HHcy) is high in critically ill patients. However, the association between serum homocysteine level and outcomes of the critically ill patients remains unknown. We performed a meta-analysis of cohort studies to comprehensively evaluate the above association. Relevant cohort studies were identified by search of electronic databases including PubMed, Embase, Web of Science, Wanfang, and CNKI from the inception of the databases to February 5, 2022. A randomized-effect model incorporating the possible between-study heterogeneity was used to pool the results. Overall, 16 cohorts with 1663 critically ill patients who were admitted to the intensive care unit (ICU) were involved in the meta-analysis. Pooled results showed that compared to non-survivors of the critical illnesses, survivors had significantly lower serum level of Hcy at ICU admission [mean difference (MD): -3.42 µmol/l, 95% confidence interval (CI): -5.89 to 0.94, p=0.007; I2=86%]. Subgroup analysis showed that the difference of Hcy between survivors and non-survivors was significant in Asian patients (MD: -8.17 µmol/l, p<0.001), but not in non-Asians (MD: 0.30 µmol/l, p=0.62; p for subgroup difference<0.001). Moreover, meta-analysis with seven cohorts, all including Chinese patients, showed that HHcy at ICU admission was independently associated with a higher risk of all-cause mortality in critically ill patients (odds ratio: 2.99, 95% CI: 2.26 to 3.97, p<0.001; I2=69%). A higher serum level of Hcy at ICU admission may be associated with an increased risk of all-cause mortality in critically ill patients, particularly in the Chinese population.

The role of methylenetetrahydrofolate reductase C677T gene polymorphism as a risk factor for coronary artery disease: a cross-sectional study in the Sidoarjo Regional General Hospital.

Introduction: hyperhomocysteinemia (HHcy) may contribute to an increased risk of coronary artery disease (CAD). The underlying mechanisms are not well understood, but other than dietary intake factors, hyperhomocysteinemia may genetically result from a methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism. A cross-sectional study was performed to assess whether this mutation was a potential genetic risk factor for CAD. Methods: this cross-sectional study was performed on 30 CAD patients and 30 normal healthy controls at Sidoarjo Regional General Hospital. The polymorphisms of the MTHFR C677T gene was assessed by polymerase chain reaction (PCR), and plasma homocysteine was measured by chemiluminescence immunoassay (CLIA) and then compared between CAD patients and control subjects by the multivariate logistical regression model. Results: results from an independent sample t-test analysis showed that plasma homocysteine concentrations were significantly higher in CAD patients compared to the control group individuals (13.91 ± 4.55 µmol/L vs 10.97 ± 3.45 µmol/L; p<0.05). There were no significant correlations between MTHFR C677T gene polymorphism and other risk factors, such as age at diagnosis with acute coronary syndrome, sex, smoking, lipid profile, diabetes, hypertension, C-reactive protein (CRP), creatinine, and homocysteine (p>0.05). In multivariate analysis models, the C677T genotype frequencies were insignificantly different between CAD patients and control subjects (p>0.05). Meanwhile, the results of adjusted odds ratio (aOR), 95% confidence interval (CI), and p-value for homocysteine, age, and smoking were aOR: 1.264, 95% CI : 1.042-1.535, p = 0.018; aOR: 0.916, 95% CI: 0.842-0.997, p = 0.043, and aOR: 5.428, 95% CI 1.532-19.226, p = 0.009, respectively. Homocysteine, age, and smoking were significantly different between CAD patients and control subjects (p<0.05). Conclusion: hyperhomocysteinemiais significantly correlated with an increased risk of CAD, but MTHFR C677T gene polymorphism might not contribute to increased CAD risk.

Folate metabolism abnormalities in infertile patients with endometriosis.

Background: Homocysteine levels can be impacted by enzymes variations. Aim: To correlate MTHFR, MTR and MTRR variants with homocysteine levels in the blood and follicular fluid and assisted reproduction results. Material & methods:MTHFR (rs2274976, rs1801131, rs1801133), MTR (rs1805087) and MTRR (rs1801394) genotyping was performed by TaqMan assays and compared with homocysteine levels, measured by ELISA, to oocytes retrieved and to the pregnancy status of women with endometriosis and controls. Results: The MTR G allele and GG genotype were more common in patients with endometriosis. They also showed lower levels of homocysteine and more clinical gestations. Epistasis analysis showed a model associated with gestational results, composed of MTHFR+MTR variants (CC+AG). Conclusion: The summation effect of variants in genes participating in folate metabolism was associated with pregnancy status in Brazilian women. MTR variants were more observed in endometriosis patients, as well as lower follicular Hcy levels and increased clinical pregnancy results.

What was the aim of the study? To correlate genetic variants to homocysteine levels in the blood and oocyte surrounding fluid, and the results of assisted reproduction techniques. How was the study done? A total of 152 women with endometriosis and controls with male infertility were evaluated. DNA was extracted from blood for genetic analysis, and homocysteine levels were measured from the blood and oocyte surrounding fluid. Genetic results were correlated to homocysteine levels, oocyte quality and pregnancy status. What were the results? A specific genetic marker occurred more in endometriosis patients. They also showed lower levels of homocysteine and a tendency to more clinical gestations than controls. What do the results of the study mean? Endometriosis patients showed specific genetic markers and different levels of homocysteine compared with controls. These results can be helpful to predict gestational results.

Serum homocysteine is associated with tubular interstitial lesions at the early stage of IgA nephropathy.

BACKGROUND: The association between homocysteine (Hcy) and IgA nephropathy (IgAN) is not well understood. We aimed to investigate the relationship between Hcy and clinicopathologic features in IgAN patients. METHODS: A total of 337 IgAN patients and 150 sex- and age- matched healthy controls were enrolled in this single-center retrospective study. According to Hcy ≤ 10 µmol/L or > 10 µmol/L, patients were divided into low and high Hcy groups. Multivariate logistic regression was performed to explore the risk factors for elevated Hcy. RESULTS: Serum Hcy was higher in IgAN patients than in healthy controls [11.6 (9.1,15.3) vs. 8.8 (7.5,10.6) µmol/L, P < 0.001], unanimously in the subgroup of 156 patients with a normal estimated glomerular filtration rate (eGFR) (≥ 90 ml/min/1.73 m2) [9.9 (7.6,12.4) vs. 8.8 (7.5,10.6) µmol/L, P < 0.001]. Compared to the low Hcy group, serum creatinine (Scr), blood urine nitrogen (BUN), uric acid (UA), endocapillary hypercellularity (E) and tubular atrophy/interstitial fibrosis lesion (T) were higher in the high Hcy group. Hcy levels were positively correlated with Scr, BUN, UA, 24-h urine protein, and E and T lesions, but negatively correlated with eGFR and superoxide dismutase (SOD). In the subgroup with normal eGFR, patients with higher Hcy were persistent with higher Scr, BUN and T lesions. A multivariate logistic regression model showed that the risk of elevated Hcy in patients with pathological T increased by 2.87-fold. T lesions could better predict high Hcy, with an odds ratio (OR) of 14.20 in the subgroup with normal eGFR. CONCLUSIONS: Pathologic T was an independent risk factor associated with elevated Hcy, especially at the early stage of IgAN.

Association Between Hyperhomocysteinemia Combined with Metabolic Syndrome and Higher Prevalence of Stroke in Chinese Adults Who Have Elevated Blood Pressure.

BACKGROUND Hyperhomocysteinemia (HHcy) and metabolic syndrome (MS) are established cardiovascular risk factors of stroke and are frequently associated with hypertension. However, studies on the association between HHcy combined with MS and stroke risk in hypertensive patients were absent. MATERIAL AND METHODS In 14 059 selected participants with elevated blood pressure, we assessed the prevalence of the MS and stroke. We defined HHcy as plasma total homocysteine >15 µmol/L. MS was defined according to the Chinese Diabetes Society (CDS) criterion. Multivariable analysis was used to examine the association of HHcy or (and) MS with stroke risk in different models. RESULTS The prevalence rates of HHcy and MS were 49.96% and 42.21%, respectively. Patients with stroke had higher plasma total homocysteine levels and a higher prevalence of MS (P<0.001). Multivariable analyses indicated that HHcy and MS are independently associated with higher prevalence of stroke (adjusted-odds ratio (OR): 1.36, 95% CI 1.17 to 1.58, P<0.001; adjusted-OR: 1.68, 95% CI 1.44 to 1.96, P<0.001, respectively). Those with combined HHcy and MS had higher odds of stroke than those with isolated HHcy or MS (adjusted-OR: 1.78, 95% CI 1.47 to 2.15, P<0.001; adjusted-OR: 1.39, 95% CI 1.13 to 1.70, P=0.002, respectively). CONCLUSIONS HHcy combined with MS was associated with higher prevalence of stroke in Chinese adults with elevated blood pressure.

Effects of individualized administration of folic acid on prothrombotic state and vascular endothelial function with H-type hypertension: A double-blinded, randomized clinical cohort study.

BACKGROUND: Hypertension and hyperhomocysteinemia (HHcy) have long been associated with adverse cardiovascular and cerebrovascular health outcomes. This study evaluated the effect of individualized administration of folic acid (FA) on homocysteine (Hcy) levels, prothrombotic state, and blood pressure (BP) in patients with H-type hypertension (combination of HHcy and hypertension). METHODS: In this double-blinded, randomized clinical cohort study, 126 patients with H-type hypertension who were treated at our hospital were randomly divided into treatment and control groups (n = 55 each). The control group was treated with oral levamlodipine besylate tablets 2.5 mg and placebo, once a day (in the morning). The treatment group was first treated with oral levamlodipine besylate 2.5 mg and FA tablets 0.8 mg, once a day (in the morning), for 12 weeks. Then, in a second 12-week phase, the FA dose was adjusted using the methylene tetrahydrofolate reductase C677 polymorphism genotype. The levels of Hcy and coagulation factors, prothrombotic state parameters, BP, and adverse drug reactions were compared between the 2 groups. RESULTS: Pretreatment general patient characteristics, including Hcy levels, were similar between the 2 groups (P > .05). BP and prothrombotic status did not differ before and after the first phase of treatment (P > .05). However, Hcy and endothelin-1 (ET-1) levels decreased, while nitric oxide levels increased significantly in the intervention group (P < .05). In the second phase, after 3 months' treatment with an FA dose adjusted according to methylene tetrahydrofolate reductase C677T genotype, the Hcy and ET-1/NO levels were significantly decreased in the intervention group and were lower than those after the first treatment phase and lower than in the control group (P < .01). BP, D-dimer levels, and fibrinogen scores were significantly lower after the second treatment phase (P < .01). There was no significant difference in the incidence of adverse drug reactions between the 2 groups (P > .05). CONCLUSIONS: Individualized administration of FA tablets can effectively reduce BP, and Hcy and coagulation factor levels, and significantly improve prothrombotic status in patients with H-type hypertension.

A High-Methionine Diet for One-Week Induces a High Accumulation of Methionine in the Cerebrospinal Fluid and Confers Bipolar Disorder-like Behavior in Mice.

Methionine (Met) is considered the most toxic amino acid in mammals. Here, we investigated biochemical and behavioral impacts of ad libitum one-week feeding of high-Met diets on mice. Adult male mice were fed the standard rodent diet that contained 0.44% Met (1×) or a diet containing 16 graded Met doses (1.2×-13×). High-Met diets for one-week induced a dose-dependent decrease in body weight and an increase in serum Met levels with a 2.55 mM peak (versus basal 53 µM) on the 12×Met diet. Total homocysteine (Hcy) levels were also upregulated while concentrations of other amino acids were almost maintained in serum. Similarly, levels of Met and Hcy (but not the other amino acids) were highly elevated in the cerebrospinal fluids of mice on the 10×Met diet; the Met levels were much higher than Hcy and the others. In a series of behavioral tests, mice on the 10×Met diet displayed increased anxiety and decreased traveled distances in an open-field test, increased activity to escape from water soaking and tail hanging, and normal learning/memory activity in a Y-maze test, which were reflections of negative/positive symptoms and normal cognitive function, respectively. These results indicate that high-Met ad libitum feeding even for a week can induce bipolar disorder-like disease models in mice.