Serum Hcy Research Articles

385Prospective associations between serum homocysteine, folate, vitamin B12 and risk of metabolic syndrome

Abstract Background Both elevated homocysteine (Hcy) and metabolic syndrome (MetS) are associated with cardio-metabolic disease. However, the potential causality in the association between Hcy and MetS is unclear, and there is uncertainty about the importance of serum level of folate and vitamin B12 for MetS. The aim of this study was to determine the prospective associations between serum homocysteine, folate and vitamin B12, and incidence of MetS in a community-based cohort of Korean adults aged ≥ 40 years. Methods We measured serum Hcy, folate and vitamin B12 in 2,895 participants (1,187 men and 1,708 women) who did not have MetS. During follow-up (10,043 person-years), 471 MetS cases were newly diagnosed. Results Higher Hcy levels were positively associated with risk of MetS (adjusted incidence rate ratio, IRR 1.87; 95% CI, 1.07–3.25 for ≥15 compared with <10 μmol/L of Hcy in men; IRR 1.81; 95% CI, 1.06–3.08 for ≥10 compared with <5 μmol/L of Hcy in women). However, serum folate was not associated with MetS, and higher serum vitamin B12 levels were associated with a statistically significant protection of MetS in men only (IRR 0.61; 95% CI, 0.42–0.90; P for trend=0.0082 in the highest tertile). Conclusions Hcy levels were positively associated in men and women, and serum vitamin B12 was inversely associated with risk of MetS in men but not in women. Serum folate do not seem to be a protective marker for MetS. Key messages Our results extend previously reported associations of Hcy with MetS, and the absence of associations of folate with MetS.

Implication of N-Methyl-d-Aspartate Receptor in Homocysteine-Induced Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a leading cause of vision loss. Elevated homocysteine (Hcy) (Hyperhomocysteinemia) (HHcy) has been reported in AMD. We previously reported that HHcy induces AMD-like features. This study suggests that N-Methyl-d-aspartate receptor (NMDAR) activation in the retinal pigment epithelium (RPE) is a mechanism for HHcy-induced AMD. Serum Hcy and cystathionine-β-synthase (CBS) were assessed by ELISA. The involvement of NMDAR in Hcy-induced AMD features was evaluated (1) in vitro using ARPE-19 cells, primary RPE isolated from HHcy mice (CBS), and mouse choroidal endothelial cells (MCEC); (2) in vivo using wild-type mice and mice deficient in RPE NMDAR (NMDARR−/−) with/without Hcy injection. Isolectin-B4, Ki67, HIF-1α, VEGF, NMDAR1, and albumin were assessed by immunofluorescence (IF), Western blot (WB), Optical coherence tomography (OCT), and fluorescein angiography (FA) to evaluate retinal structure, fluorescein leakage, and choroidal neovascularization (CNV). A neovascular AMD patient’s serum showed a significant increase in Hcy and a decrease in CBS. Hcy significantly increased HIF-1α, VEGF, and NMDAR in RPE cells, and Ki67 in MCEC. Hcy-injected WT mice showed disrupted retina and CNV. Knocking down RPE NMDAR improved retinal structure and CNV. Our findings underscore the role of RPE NMDAR in Hcy-induced AMD features; thus, NMDAR inhibition could serve as a promising therapeutic target for AMD.

Homocysteine is an indicator of arterial stiffness in Chinese women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is associated with an increased risk of cardiovascular disease in women. Hyperhomocysteinemia (H-Hcy) is closely related to arterial stiffness (AS) in patients with cardiovascular disease. This study aimed to investigate the relationship between serum homocysteine(Hcy) level and brachial-ankle pulse wave velocity (baPWV) in Chinese women with PCOS. A total of 124 PCOS women were enrolled and divided into two groups according to their baPWV values: normal, baPWV < 1400 cm/s and high AS, baPWV ≥ 1400 cm/s. Univariate analysis was performed to investigate the relative factors for baPWV, and multiple regression analysis was used to evaluate the association of Hcy with baPWV. The group with high AS (n = 35) had higher Hcy levels than the other group (n = 89; P < 0.05). Moreover, univariate analysis revealed that serum Hcy was positively correlated with baPWV (r = 0.133, P < 0.01). In multiple regression analysis, the age-adjusted serum Hcy level was positively correlated with baPWV (β = 0.201, P < 0.01). It remained positively associated with baPWV (β = 0.145, P < 0.01) after further adjustments for age, BMI, PCOS duration, systolic blood pressure, and homeostasis model assessment-insulin resistance as well as several other factors correlated with baPWV. Our results demonstrated that H-Hcy was significantly and independently related to elevated baPWV, suggesting that Hcy might play a role in the pathologic process of AS in women with PCOS. Further researches with more subjects are needed to explore whether Hcy would be a promising biomarker for the stratification management of PCOS women.

The Auxiliary Diagnostic Value of Serum Adenosine Deaminase in Acute Leukemia at Clinical Test

To investigate the auxiliary diagnostic value of serum adenosine deaminase (ADA) in acute leukemia (AL) at clinical test. 123 AL patients hospitalized in Zhejiang hospital from November 2018 to March 2020 were enrolled as the observation group, and 98 healthy people in the same period were randomly enrolled as the control group. AL patients were divided into two groups: 77 acute myeloid leukemia (AML) patients for AML group and 46 acute lymphoblastic leukemia (ALL) patients for ALL group. The levels of adenosine deaminase (ADA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH) and homocysteine (Hcy) in serum of the patients were detected, and the correlation of ADA with these items was analyzed. Receiver operating characteristic curve (ROC) was used to analyze the clinical diagnostic value of ADA, Yoden index was used to confirm the best cut-off point. The serum ADA level in AL patients was significant higher than that in control group (P < 0.05). The results of Pearson correlation analysis showed that there was a significant positive correlation of ADA with Hcy, ALT, AST, GGT, LDH in AML group (r = 0.47, r = 0.28, r = 0.37, r = 0.22, r = 0.55); and also there was a significant positive correlation of ADA with GGT in ALL group (r = 0.54). In AML group, the maximum area under ROC curve was 0.761 (P = 0.00), 95% confidence interval was 0.682-0.841, sensitivity was 54.50%, specificity was 98.90%, and the best cut-off point was 17.1 U/L. In ALL group, the maximum area under ROC curve was 0.785, 95% confidence interval was 0.694-0.877, sensitivity was 65.90%, specificity was 84.00%, and the best cut-off point was 13.45 U/L. The detection of ADA in serum can be used as an auxiliary examination in patients with AL, which can provide a certain value for the diagnosis of the disease.

The dual impact of homocysteine and cholesterol on cognitive functions

Background There is some debate about the role of cholesterol in cognitive functions. Cholesterol has been accused of its deleterious effect on cognitive functions since decades. Others talked about its beneficial outcomes on cognition. Aim The aim of the study was to find the correlation between total cholesterol (TC) and cognitive functions and if it is homocysteine (Hcy) dependent. Participant and methods We enrolled 41 individuals, aged 55 years old and over. All participants underwent measurement of serum Hcy and TC and other lipid profile components. Assessment of cognitive functions was done by two batteries: Mini-Mental State Exam (MMSE) and Memory Assessment Scale (MAS). Results Forty participants were found to have normal Hcy levels (2.499 ± 0.77 μmol/l). According to the TC level, the participants were divided into three tertiles, in those with the highest TC (>181 mg/dl) there was a direct significant correlation between TC and cgnitive functions as follows: MMSE (P = 0.01), total MAS score (P = 0.04), verbal memory (P = 0.01), and visual memory (P = 0.03). Also, it was noticed that MMSE (P = 0.03), total MAS (P = 0.03), verbal memory (P = 0.04), and visual memory (P = 0.02) had significant positive correlations with high-density lipoprotein cholesterol. Also, MMSE (r = 59, P = 0.00) and total MAS (r = −0.39, P = 0.01) had significant negative correlation with low-density lipoprotein cholesterol. Conclusion High serum TC levels, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol may have protective effects on cognitive functions. However, the authors could not confirm if there is a dual correlation between serum TC and Hcy levels on cognitive functions, as all the participants had normal Hcy levels.

Age-Dependent Association Between Elevated Homocysteine and Cognitive Impairment in a Post-stroke Population: A Prospective Study.

Background and Purpose: The results regarding the independent association between homocysteine (Hcy) levels and post-stroke cognitive impairment (PSCI) were inconsistent. The effect of age on this association has yet to be explored. This study aims to determine the relationship between Hcy levels, age, and cognitive impairment in a post-stroke population.Methods: A total of 592 patients with acute ischemic stroke (AIS) completed follow-up. Serum Hcy levels were measured enzymatically by spectrophotometry within 24 h of admission. Cognitive function was evaluated by the Mini-Mental State Examination (MMSE) 1 month after stroke, and the scores ≤ 24 were considered as cognitive impairment. Our study was dichotomized into two groups by a cut-off of 65 years. Multivariate logistic regression models were used to determine the association between baseline Hcy levels and cognitive impairment.Results: According to the MMSE score, 317 (53.5%) patients had cognitive impairment. Patients with higher levels of Hcy were more prone to have cognitive impairment 1 month after stroke than patients with lower levels of Hcy (p < 0.001). The optimal cut-off points of Hcy level (μmol/L) were (T1) ≤ 8, (T2) 8–12, and (T3) ≥ 12. After adjusting for confounding factors, the multivariate regression analysis showed that the third Hcy tertile was independently associated with cognitive impairment [odds ratio (OR) = 2.057, 95% confidence interval (CI) = 1.133–3.735, p = 0.018). A stronger association [T2 (OR = 2.266, 95% CI = 1.042–4.926, p = 0.039); T3 (OR =3.583, 95% CI = 1.456–8.818, p = 0.005)] was found in the younger group. However, the independent association was not confirmed in the older group.Conclusions: Elevated Hcy levels in the acute phase of ischemic stroke were independently associated with cognitive impairment in a post-stroke population. Furthermore, the association was age-dependent and more meaningful in a younger population aged below 65. So, Hcy levels in patients with stroke should be well-monitored, especially in younger patients.

Mild hyperhomocysteinemia induces blood-brain barrier dysfunction but not neuroinflammation in the cerebral cortex and hippocampus of wild-type mice.

This study explored the potential effects of mild hyperhomocysteinemia (HHcy) on the blood-brain barrier (BBB) and neuroinflammation. Seven-week-old male wild-type C57BL/6 mice were fed normal mouse chow (the control group) or a methionine-enriched diet (the HHcy group) for 14 weeks. Mice in the HHcy group exhibited a slight increase in serum Hcy levels (13.56 ± 0.61 μmol/L). Activation of the ERK signaling pathway, up-regulation of matrix metalloproteinase-9 (MMP-9), and degradation of tight junction proteins (occludin and claudin-5) were observed in both the cerebral cortex and hippocampus of mice with mild HHcy. However, microglia were not activated and the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were not changed in either the cerebral cortex or hippocampus of mice with mild HHcy. Moreover, the signaling activity of STAT3 also did not differ significantly between the two groups. These findings demonstrate that the BBB is highly vulnerable to homocysteine insult. Even a slight increase in serum homocysteine levels up-regulates MMP-9 expression and disrupts the BBB integrity. Meanwhile, microglia activation or the STAT3 pathway might not contribute to the effects of mild HHcy on the brain.

Genetic Polymorphisms in Enzymes Involved in One-Carbon Metabolism and Anti-epileptic Drug Monotherapy on Homocysteine Metabolism in Patients With Epilepsy.

Aims: To investigate the effects of single nucleotide polymorphisms (SNPs) in genes of one-carbon metabolism (OCM) related enzymes and anti-epileptic drug (AED) monotherapy on homocysteine (Hcy) metabolism in patients with epilepsy, and to further explore specific SNPs that may increase patients' susceptibility to the effects of AEDs on the Hcy imbalance.Method: This case-control study analyzed 279 patients with epilepsy, including patients receiving monotherapy with valproate (VPA) (n = 53), oxcarbazepine (OXC) (n = 71), lamotrigine (LTG) (n = 55), or levetiracetam (LEV) (n = 35) and patients who had not taken any AEDs (controls, n = 65) for at least 6 months. Serum levels of vitamin B12 (vit B12), folate (FA) and Hcy were measured, and 23 SNPs in 13 genes of OCM-related enzymes were genotyped in all patients.Results: Methylenetetrahydrofolate reductase (MTHFR) rs1801133 was associated with elevated serum Hcy levels in patients with epilepsy (P < 0.001), and patients presenting the TT genotype exhibited higher serum Hcy levels than patients with the CC (P < 0.001) or CT (P < 0.001) genotype. A subsequent multiple linear regression analysis showed that AED monotherapy with VPA (vs. control: P = 0.023) or OXC (vs. control: P = 0.041), and genotypes of MTHFR rs1801133 TT (vs. CC: P < 0.001; vs. CT: P < 0.001), transcobalamin 2 (TCN2) rs1801198 CC (vs. GC: P = 0.039) and folate receptor 1 (FOLR1) rs2071010 AA (vs. GA: P = 0.031) were independent risk factors for higher Hcy levels. In the subgroup analysis of patients taking OXC, we found that patients with genotypes of MTHFR rs1801133 TT (vs. CC: P = 0.001; vs. CT: P < 0.001) and TCN2 rs1801198 CC (vs. GC: P = 0.021; vs. GG: P = 0.018) exhibited higher serum Hcy levels.Conclusions: VPA, OXC, and genotypes of MTHFR rs1801133 TT, TCN2 rs1801198 CC, and FOLR1 rs2071010 AA are all independent risk factors for elevated Hcy levels in patients with epilepsy. Moreover, genotypes of MTHFR rs1801133 TT and TCN2 rs1801198 CC may increase patients' susceptibility to the effect of OXC on disrupting Hcy homeostasis.

Homocysteine is potential serological marker for predicting the risk of deep venous thrombosis of the lower extremities in patients received operation of lower limb fracture

Abstract Objective The aim of the study is to investigate the correlations among serum homocysteine (Hcy), D-dimer, and the risk of developing deep venous thrombosis (DVT) of the lower extremities in patients who underwent operation for lower limb fracture. Methods Seventy-five cases who underwent operation for lower limb fracture were included and further divided into DVT group (n = 26) and control group (n = 49) based on post-DVT diagnostic criteria. The serum Hcy and D-dimer were examined 48 h after operation. The serum Hcy and D-dimer levels were compared between the two groups. The correlation between serum Hcy and D-dimer was investigated by the Pearson correlation test. The receiver-operating characteristic (ROC) curve was applied to evaluate the diagnostic performance of serum Hcy and D-dimer as serological markers for DVT. Results The serum Hcy concentrations were 11.96 ± 3.98 μmol/L and 7.92 ± 3.27 μmol/L for DVT and control groups, respectively, with statistical difference (t = 4.72, P &lt; 0.01). The serum D-dimer in the DVT group was significantly higher than that of the control group (8.99 ± 4.50 vs 1.70 ± 2.11) μg/mL with statistical difference (t = 9.56, P &lt; 0.01). Line regression analysis indicated that serum Hcy was positively correlated with serum D-dimer concentration and can be demonstrated by the equation of Y = 0.6651*X + 1.036 for the DVT group. Using serum Hcy as the biomarker for predicting DVT, the prediction sensitivity and specificity were 76.92 and 71.44%, respectively, with the AUC of 0.7804 under the cut-point of 9.54 μmol/L. For serum D-dimer, the prediction sensitivity and specificity were 96.15 and 73.47%, respectively, with the area under the ROC (AUC) of 0.9455 under the cut-point of 1.66 μg/mL. Conclusion Serum Hcy was significantly elevated in DTV patients, and hence, it can be applied as a serological marker for DVT prediction in patients who underwent operation for lower limb fracture. However, the DVT prediction performance of serum Hcy was inferior to D-dimer especially for diagnostic sensitivity.

Serum Homocysteine Level Is a Predictor of Relapse and Prognosis in Patients With First-Attack Neuromyelitis Optica Spectrum Disorders.

Background: Many patients with neuromyelitis optica spectrum disorders (NMOSD) experience the adverse consequences of relapse and disability aggravation. Thus, it is necessary to identify sensitive and reliable biomarkers for early prognosis. This study investigated whether serum homocysteine (Hcy) level was associated with the risk of relapse or poor prognosis in first-attack NMOSD patients.Methods: We enrolled 161 first-attack NMOSD patients in this retrospective study. We reviewed their medical records and evaluated their initial Expanded Disability Status Scale (EDSS). Clinical outcomes were measured by the final EDSS and the relapse rate. The association between Hcy levels and EDSS score at last follow-up was analyzed by binary logistic regression. The association between Hcy levels and relapse rate was assessed by Cox regression analysis. Receiver operating characteristic (ROC) curve analysis was used to predict the target value of Hcy reduction.Results: Compared with the high Hcy group, the final EDSS score in the low Hcy group was significantly lower (median: 0.5 vs. 2.5, P < 0.001). The relapse rate differed significantly between these groups (30.6 vs. 50.0%, P = 0.023). Multivariate analysis showed that the initial EDSS score (odds ratio [OR] 3.03, 95% confidence interval [CI] 2.07–4.45, P < 0.001) and serum Hcy level (OR 1.13, 95%CI 1.04–1.22, P = 0.002) were significantly associated with poor prognosis in NMOSD patients. Additionally, multivariate analysis showed that serum Hcy level (hazard ratio 1.06, 95%CI 1.04–1.09, P < 0.001) was an independent predictor of the risk for relapse in NMOSD. The 12-month relapse rate of the high Hcy group was 34.8%, and 50% of high Hcy patients relapsed within 35 months after the first onset. A serum Hcy level exceeding 14.525 μmol/L indicated a high risk of relapse, with a sensitivity of 43.7%, specificity of 90.0%, and area under the ROC curve of 0.674 (95%CI 0.59–0.76, P < 0.001).Conclusion: Serum Hcy level is an independent predictor of relapse and poor prognosis in first-attack NMOSD patients. Early monitoring and reduction of serum Hcy levels may be of great significance in the prevention of disease relapse and severe disability.

Association between homocysteine and white matter hyperintensities in rural-dwelling Chinese people with asymptomatic intracranial arterial stenosis: A population-based study.

PurposeAlthough homocysteine (Hcy) has been proven to be associated with the incidence of white matter hyperintensities (WMH) in patients with stroke, this association remains unclear in participants with asymptomatic intracranial arterial stenosis (aICAS). This study aimed to investigate the association of Hcy with WMH in participants with aICAS.Materials and methodsThis was a cross‐sectional study based on the Kongcun Town Study. Participants diagnosed with aICAS by magnetic resonance angiography in the Kongcun Town Study were enrolled in this study. Data on demographics, lifestyle, medical histories, and Hcy levels were collected via interviews, clinical examinations, and laboratory tests. The volume of WMH was calculated using the lesion segmentation tool system for the Statistical Parametric Mapping package based on magnetic resonance imaging. The association between Hcy and WMH volume was analyzed using linear and logistic regression analyses.ResultsA total of 137 aICAS participants were enrolled in the present study. Hcy was associated with the incidence of severe WMH (4th quartile, ≥4.20 ml) after adjustment for certain covariates [Hcy as a continuous variable, odds ratio (95% confidence interval) (OR (95% CI)): 1.09 (1.00, 1.19), p = .047; as a categorical variable (Hcy ≥15 μmol/L), OR (95% CI): 3.74 (1.37, 10.19), p = .010)]. After stratification according to the degree of aICAS, this relationship remained significant only in the moderate‐to‐severe stenosis group (stenosis ≥50%). (Hcy as continuous variable, OR (95% CI): 1.14 (1.02, 1.27), p = .025; as a categorical variable (Hcy ≥15 μmol/L), OR (95% CI): 5.59 (1.40, 15.25), p = .015).ConclusionSerum Hcy concentration may be positively associated with the volume of WMH in rural‐dwelling Chinese people with moderate‐to‐severe (stenosis ≥50%) aICAS.

Levels and clinical significance of serum homocysteine (Hcy), high-density lipoprotein cholesterol (HDL-C), vaspin, and visfatin in elderly patients with different types of coronary heart disease.

To investigate the levels and clinical significance of serum homocysteine (Hcy), high-density lipoprotein cholesterol (HDL-C), visceral adipose tissue-derived serine protease inhibitor (vaspin), and visceral fat-specific adipokine (visfatin) in elderly patients with different types of coronary heart disease (CHD). A total of 208 elderly patients with CHD admitted to our hospital were selected as the observation group, and 57 healthy volunteers who received physical examinations during the same period were selected as the healthy control group. The patients in the observation group were divided into a stable angina pectoris (SAP) group, an unstable angina pectoris (UAP) group, and an acute myocardial infarction (AMI) group according to their clinical diagnosis. The levels of serum Hcy, HDL-C, vaspin, visfatin, and coronary angiography Gensini scores were compared among the CHD subgroups and the healthy control group. Pearson linear correlation analysis was used to analyze the correlation between levels of serum Hcy, HDL-C, vaspin, and visfatin with Gensini scores in elderly patients with different types of CHD. The levels of serum Hcy and visfatin in the observation group were significantly higher than those in the healthy control group (P<0.05), while the levels of serum HDL-C and vaspin were significantly lower than those in the healthy control group (P<0.05). There were statistically significant differences in the levels of serum Hcy, vaspin, and visfatin among the CHD subgroups (P<0.05). There were statistically significant differences in the Gensini scores and number of stenotic coronary arteries among the CHD subgroups (P<0.05). Pearson linear correlation analysis showed that the levels of serum Hcy, HDL-C, vaspin, and visfatin in the SAP group were not significantly correlated with Gensini scores (P>0.05). However, the levels of serum Hcy and visfatin in the UAP and AMI groups were positively correlated with Gensini scores (P<0.05), the level of serum vaspin was negatively correlated with Gensini scores (P<0.05). The levels of serum Hcy, vaspin, and visfatin vary according to the different types of CHD and are correlated with the degree of coronary artery stenosis. As such, these serum levels can be used as sensitive indicators for early detection and disease evaluation.

Changes of Serum Sex Hormone-Binding Globulin, Homocysteine, and Hypersensitive CRP Levels during Pregnancy and Their Relationship with Gestational Diabetes Mellitus

Background: Inflammatory response state is related to the pathogenesis of gestational diabetes mellitus (GDM). Objective: To investigate the changes of serum sex hormone-binding globulin (SHBG), homocysteine (Hcy), and hypersensitive CRP (hs-CRP) levels during pregnancy and their relationship with GDM. Methods: The nested case-control study method was used. Sixty nonobese single pregnant women diagnosed with GDM were divided into the GDM group (GDM, n = 60), together with another 60 pregnant women with normal glucose tolerance who were matched in the same period and divided into the control group (control, n = 60). The serum Hcy, hs-CRP, and SHBG levels were measured. Results: The serum levels of Hcy and hs-CRP were significantly higher in the GDM group compared with the control group, and serum levels of SHBG was significantly lower in the GDM group compared with the control group at different stages of pregnancy. The serum levels of Hcy and hs-CRP in pregnant women increased with the increase of gestational age, and serum levels of SHBG decreased with the increase of gestational age. Increased Hcy and hs-CRP levels in the second trimester and decreased SHBG levels in the first trimester were related to GDM. The odds ratio (OR) and 95% confidence interval (CI) were as follows: OR: 4.5, 95% CI: 1.5–13.0; OR: 4.2, 95% CI: 1.5–10.1; and OR: 0.4, 95% CI: 0.3–0.7, respectively. Conclusion: Increased Hcy and hs-CRP in the second trimester and decreased SHBG in the first trimester were independent predictors of GDM, which provides a new idea for early prevention and treatment of GDM.

Association of homocysteine with IVF/ICSI outcomes stratified by MTHFR C677T polymorphisms: a prospective cohort study

Research questionWhat is the association between homocysteine (Hcy) and IVF/intracytoplasmic sperm injection (ICSI) outcomes, stratified by methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms? DesignThis prospective cohort study recruited 1011 infertile women undergoing IVF/ICSI treatment for the first time at the International Peace Maternity and Child Health Hospital between June 2015 and March 2018. ResultsThe concentration of total serum Hcy was significantly negatively associated with clinical pregnancy and implantation rate. When adjusted for maternal and paternal age and educational level, maternal body mass index, and FSH and oestradiol concentrations, logistic regression analysis showed that women with higher Hcy had a higher risk of unsuccessful pregnancy. After stratification by MTHFR C677T polymorphisms and adjustment for confounding factors, a higher risk of unsuccessful pregnancy and a significantly lower implantation rate only existed in women with higher Hcy concentration in the MTHFR C677T TT genotype. There was no significant association between Hcy concentrations and other ovarian stimulation outcomes (oocytes retrieved, metaphase II stage oocytes, fertilization rate, cleavage rate, high-quality embryo rate) or neonatal outcomes (preterm birth, gestational age at delivery, Caesarean section, birthweight, small for gestational age, large for gestational age or birth defects). ConclusionsHcy is highly negatively associated with clinical pregnancy and implantation rate during the first IVF/ICSI cycle, especially in women carrying the MTHFR C677T TT genotype. Other factors with impacts on reproductive outcomes, such as stage of embryo transferred, other factors involved in folate metabolism, preimplantation genetic testing, etc., should be taken into account in further research.

Relation of kidney function and homocysteine in patients with hypothyroidism.

Objective It has been found that both serum homocysteine (Hcy) and serum creatinine levels were increased in hypothyroidism patients. The aim of this study was to investigate the correlation between serum Hcy and kidney function in patients with subclinical hypothyroidism or hypothyroidism. Methods A total of 448 subjects were enrolled and divided into three groups: hypothyroidism (n = 129), subclinical hypothyroidism (n = 141), and control group (n = 168). Anthropometric information, metabolic parameters, serum Hcy and creatinine levels, and estimated glomerular filtration rate (eGFR) were analyzed. Results Compared with healthy subjects, patients with subclinical hypothyroidism or hypothyroidism had significantly higher serum Hcy and creatinine levels and lower eGFR level (all P < 0.001). Serum Hcy was negatively correlated with eGFR in subclinical hypothyroidism patients (r = −0.220, P = 0.009), and in hypothyroidism patients (r = −0.422, P < 0.001). After adjusting for age, sex and BMI, eGFR was still significantly correlated with serum Hcy in subclinical hypothyroidism or hypothyroidism patients (both P < 0.05). Levothyroxine treatment resulted in significantly decreased Hcy and increased eGFR in hypothyroidism patients (both P < 0.001). The decrease in Hcy was correlated with the increased eGFR after treatment (P = 0.001). Conclusion Serum Hcy was negatively correlated with eGFR in subclinical hypothyroidism or hypothyroidism patients. After levothyroxine treatment, a correlation was found between the decrease in serum Hcy and the increase in eGFR in hypothyroidism patients.

High Methionine Diet-Induced Alzheimer's Disease like Symptoms Are Accompanied by 5-Methylcytosine Elevated Levels in the Brain.

Background Excessive or insufficient intake of methionine (Met) causes neuronal dysfunction, neurodegeneration, cerebrovascular dysfunction, vascular leakage, and short-term memory loss, which result in the occurrence of Alzheimer's disease- (AD-) like symptoms. Objective To determine the relationship between high methionine diets (HMD) induced AD-like symptoms and 5-methylcytosine (5-mC) level. Methods C57BL/6J mice were randomly divided into two groups: the control group (Maintain diets) and the model group (2% HMD). Mice were fed with 2% HMD for 9 weeks. Animals were weighed and food intake was recorded weekly. Open field test, nesting ability test, Y maze test, new object recognition test, and Morris water maze test were used to detect the motor, learning, and memory ability. Hematoxylin-eosin (HE) staining was used to observe the damage of cells in hippocampus and cortex. Immunofluorescence (IF) staining was used to detect the expression and distribution of amyloid-β 1-40 (Aβ1-40), amyloid-β 1-42 (Aβ1-42), and 5-methylcytosine (5-mC) in hippocampus and cortex. Western blotting (WB) was used to determine the expression of Aβ and DNA methyltransferases- (DNMTs-) related proteins in the cortex. Enzyme-linked immunosorbent assay (ELISA) was performed to detect homocysteine (Hcy) level (ELISA). Results Feeding of HMD decreased the body weight and food intake of mice. Behavioral testing revealed that HMD caused learning, memory, and motor ability impairment in the mice. HE staining results showed that HMD feeding caused damage of hippocampal and cortical neurons, along with disordered cell arrangement, and loss of neurons. Furthermore, HMD increased the contents of Aβ1-40, Aβ1-42, and 5-mC in the hippocampus and cortex. WB results showed that HMD increased the expression of Aβ production-related proteins, such as amyloid precursor protein (APP) and beta-secretase 1 (BACE1), and decreased the expression of Aβ metabolism-related protein in the cortex, including insulin-degrading enzyme (IDE) and neprilysin (NEP). Additionally, the decreased expression of DNA methyltransferase1 (DNMT1) was observed in HMD-treated mice, but there was no significant change of DNMT3a level. ELISA results showed that HMD increased the levels of Hcy in serum. Conclusion Our result suggested that the HMD can cause neurotoxicity, leading to AD-like symptoms in mice, which may be related to 5-mC elevated.

Comparative Assessment of Serum Homocysteine and High Sensitivity C-reactive Protein in type 2 Diabetic and non Diabetic Patients with ACS

Background: Increased level of serum homocysteine (Hcy) and high sensitivity C-reactive protein (hs-CRP) have a proven implication with epithelial injury leading to coronary artery disease ((CAD). These are strongly associated with different metabolic syndrome variables, although different studies have shown both positive and negative responses when correlated with type 2 diabetes malitus (T2DM). In this study we explored the role of these markers of CAD in type II diabetic and non diabetic patients with newly diagnosed acute coronary syndrome (ACS) at a tertiary care hospital among Bangladeshi population.&#x0D; Methods: We wanted to identify whether Hcy and hs- CRP link positively or negatively with type 2 diabetes in this cross sectional observentional study. A total of 260 patients with new onset ACS were included in the study, out of which 72 patients with T2DM and 188 patients without diabetes were considered as group I and group II respectively. Clinical and biochemical data were compared in between the groups.&#x0D; Results: The mean age of the study population was 50.33±15.50 years and 45.86±18.76 years in group I and II respectivly. Male female ratio was 4:1 among the whole study subjects. There was significantly higher level of serum homocysteine in group II than group I 18.41±15.49 μmol/L vs. 14.11±6.48 μmol/L respectively (p &lt;0.05). Similarly hs-CRP in group I was 26.84±30.30 mg/L and in group II 37.48±37.99mg/L, higher in group II (p&lt;0.05). Both Hcy and hs-CRP were higher in male and female patients in group II. Dyslipidaemia was significant risk factor in group I and smoking in group II (p&lt;0.05).&#x0D; Conclusion: In patients with ACS serum Hcy and hs-CRP were significantly higher in non-daibetic patients then in patients with type 2 diabetes. This association may be population or ethenicity specific which provide further scope for future elaborate studies.&#x0D; Bangladesh Heart Journal 2020; 35(2) : 114-120

Insight into the Metabolite Pattern of Psoriasis: Correlation among Homocysteine, Methionine, and Polyamines

Psoriasis is an incurable dermatological disorder, characterized by increased epidermal cell proliferation. Numerous studies have focused on the modulation of polyamine (PA) metabolism in psoriatic lesions, as well as the relationship between serum homocysteine (Hcy) levels and psoriasis severity. The correlation between Hcy and PA levels has not been investigated, although both of them depend on methionine (Met) loading. The aim of this study was to examine Met, Hcy, and polyamine levels in serum, saliva, lesions, and non-affected skin to investigate the eventual relationship between their levels in skin samples and to assess the correlation of each metabolite among the tested samples. This study was conducted on 24 patients with plaque-form psoriasis vulgaris. The original LC-MS/MS method was used for quantification of analytes. Hyperhomocysteinemia was observed and the serum levels of spermidine (Spd) and spermine (Spm) were also found to be elevated. A significant increase in Met (p &lt; 0.05) and Spm (p &lt; 0.001) concentrations in the psoriatic plaques were found, when compared to the non-affected skin. Significant correlations were established between all polyamines levels and between methionine and spermine in both types of cutaneous samples. This study illustrates the tight relationship between Met and Polyamine levels in epidermis of psoriatic patients. Our results could be helpful in psoriasis treatment, highlighting the importance of the balanced protein diet and intake of vitamins B12 and B9.

Characteristics of TCM Constitution and Related Biomarkers for Mild Cognitive Impairment.

IntroductionThe incidence of Alzheimer’s disease is on the rise, early detection of cognitive impairment of the elderly is very important. In traditional Chinese medicine, constitution is related to the susceptibility of the human body to diseases. Based on the theory of constitution of traditional Chinese medicine (TCM), the human population can be classified into 9 constitutions. However, little is known about the characteristics of medical constitution and related biomarkers in subjects with mild cognitive impairment (MCI).MethodsWe measured the TCM Constitution of 214 subjects by using the Constitution in Chinese Medicine Questionnaire (CCMQ). MMSE and MoCA were used to assess cognitive function. The subjects were divided into mild cognitive impairment group (MCI, n = 152) and normal control group (NC, n = 62). The levels of serum Hcy and serum/urine 8-iso-PGF 2α were determined.Results1) It was found that there was a significant difference in constitution types between MCI and NC. There were significant differences in MMSE and MoCA score, serum Hcy and serum/urine 8-iso-PGF 2a levels between the two groups. 2) In logistic regression analysis, the variables with statistical significance were TCM Constitution of Yang-Deficient, Phlegm-Dampness, Blood-Stasis and abnormal increase of Hcy (OR>1). 3) The MoCA scores had a positive correlation with the MMSE. A statistically significant inverse association was found between serum Hcy, blood and urine 8-iso-PGF 2a and scores of cognitive assessment in MCI.ConclusionConstitution types (Yang-Deficient, Phlegm-Dampness and Blood-Stasis) and abnormal serum Hcy elevation can be used as risk factors for MCI. MoCA scores can serve to detect MCI at early stage. Serum/urine 8-iso-PGF 2α has a certain relationship with MCI. Higher levels of serum/urine 8-iso–PGF 2α are more likely to be associated with MCI risk.

The Influence of Serum Homocysteine Level to the Prognosis of Newly Diagnosed Multiple Myeloma Patients and Analysis of Related Factors

To analyze the influence of serum homocysteine (Hcy) levels to the prognosis of newly diagnosed multiple myeloma (MM) patients, and to explore related factors affecting the prognosis of the patients. The clinical pathological data of 180 newly diagnosed MM patients treated in our hospital from March 2013 to February 2015 were collected, and the patients were divided into high and low Hcy groups based on the median Hcy. The survival curves of the patients in the two groups were drawn to compare the differences of the survival; univariate and multivariate survival analysis was used to observe the influence of serum cysteine to the prognosis of newly diagnosed MM patients; the clinicopathological data of the patients with high and low Hcy in the two groups was compared, Pearson test was used to further analyzes the relationship between Hcy and different factors, and explores the related factors of Hcy affecting the prognosis of the patients. The median survival times of patients in the high and low Hcy groups were 32 (5-59) and 41 (7-71) months, respectively. The 3-year survival rate of the patients in high Hcy group was significantly lower than those in low Hcy group, and the difference shows statistically significant (P<0.05). The results of univariate survival analysis showed that the OS of newly diagnosed MM patients whom with advanced age, high bone disease grade, high-level bone marrow plasma cell count, LDH, C-reactive protein, Cr, β2-MG, Hcy, low-level Hb, and ALB was significantly shortened (all P<0.05). The results of multivariate survival analysis showed that old age, high levels of bone marrow plasma cells, Cr, β2-MG, low levels of Hb, and ALB were the independent risk factors shorting the overall survival (OS) time of newly diagnosed MM patients (all P<0.05), while Hcy showed no independent relation for the OS of patients (P>0.05). The Hb level of the patients in high Hcy group was significantly lower than those in low-Hcy group, while the LDH level was significantly higher than those in low Hcy group (all P<0.05). Pearson test results showed that serum Hcy and Hb showed negative correlation (r=-0.813, P<0.05), but it shows positive correlation with LDH (r=0.726, P<0.05). Serum Hcy level has a correlation trend with the survival of newly diagnosed MM, which is affected by factors such as Hb.