tHcy Levels Research Articles

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.

Plasma Homocysteine Levels and Cardiovascular Events in Patients With End-Stage Renal Disease: A Systematic Review.

Patients with chronic renal disease or failure are at a heightened risk of mortality due to cardiovascular disease (CVD), which is a predominant cause of death in this population. Hyperhomocysteinemia is prevalent in patients with end-stage renal disease (ESRD), which may increase their susceptibility to CVD. We conducted a comprehensive search of PubMed, Science Direct, and Google Scholar for articles published between 2003 and February 2023, using a combination of keywords such as "plasma homocysteine levels," "hyperhomocysteinemia," "end-stage renal disease," "renal failure," "kidney failure," "cardiovascular events," "cardiovascular disease," "myocardial infarction," "coronary artery disease," and "stroke." Our inclusion criteria were studies that investigated the association between total homocysteine (Hcy) level and CVD or total mortality, as well as the impact of vitamin supplementation on cardiovascular or mortality risk. We restricted our search to English-language studies that included ESRD patients and provided data on plasma Hcylevels and associated CVD events. This systematic review includes 11 articles published between 2003 and 2023 that enrolled a total of 3,953 subjects, of whom 79.15% were male patients. All studies included in the review were either quantitative randomized trials or non-randomized studies, such as cross-sectional, cohort, or case-control studies. Of the total studies included, 10 reported either cardiovascular mortality or CVD events, including cardiovascular death, myocardial infarction (MI), angina, and stroke. One study reported the CVD risk score of the patients, and most of them had higher total homocysteine (tHcy) levels. Overall, a total of 817 CVD events were reported across the studies. In conclusion, the relationship between Hcy and cardiovascular events in ESRD patients is not straightforward and requires further research. However, our review suggests that Hcy could be a predictor of cardiovascular events in this population, and its nutritional characteristics as well as other associated comorbidities may contribute to its inverse association with outcomes.

Platelet counts affect the association between hyperhomocysteinemia and pregnancy complications

BackgroundThe joint effect of platelet and other modifiers on the risk of pregnancy complications is unknown. This study investigated whether platelet count (PC) and total homocysteine (tHcy) level have a synergistic effect on the incidence of pregnancy complications in a Chinese population.MethodsTotal 11,553 consecutive pregnant women who received whole blood cell and biochemical tests at the time of admission for labor in Changzhou Maternal and Child Health Care Hospital were analyzed. The primary outcome was the prevalence of pregnancy complications: gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy (ICP), pre-eclampsia (PE), and pregnancy induced hypertension (PIH).ResultsThe prevalence of GDM, ICP, PE, and PIH was 8.4%, 6.2%, 3.4%, and 2.1%, respectively. The highest rate of ICP (28.6%) was observed in women with high tHcy (> 15 μmol/L) and low PC (quartile 1); and the lowest rate of GDM (0.6%) was found in women with high tHcy and high PC (quartiles 2 to 4). In low PC group, the prevalence of ICP in women with high tHcy was significantly higher than that in women with low tHcy (≤ 15 μmol/L) (28.6% vs. 8.4%), representing an absolute risk increment of 20.2% and a relative risk increment of 3.3-fold (OR: 3.34; 95% CI: 1.55, 7.17; P = 0.002), whereas no joint effect was observed among high PC group.ConclusionsAmong Chinese pregnant women, one subgroup (high tHcy and low PC) has the highest risk of ICP and another (high tHcy and high PC) has the lowest risk of GDM; tHcy and platelet could be used as indicators to identify the women with high risk of ICP or low risk of GDM.

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.

FOLINIC ACID OR L-METHYLFOLATE SUPPLEMENTATION FOR THE TREATMENT OF HYPERHOMOCYSTEINEMIA

Objective: Hyperhomocysteinemia (HHcy) is recognized as a risk factor for for cardiovascular disease. The aim of this study was to investigate and compare the efficacy of two tHcy-lowering treatments including FNA or L-methylfolate in healthy Greek adults. Design and method: Two hundred and seventy two (272) health Greek adults (143 men; mean age±SD: 43.0±15.3 years), with elevated serum tHcy levels (>10 mmol/L) received randomized folinic acid (Group 1) or L-methylfolate (Group 2) orally both with hydroxycobalamine im for three months. Serum folate, Cbl and tHcy levels were determined using immunoassays methods at the beginning and the end of the study period. The MTHFR C677T and A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. Results: At the end of the 3-month intervention period the levels of serum folate and Cbl were significantly increased, whereas serum tHcy concentrations were significantly decreased in both groups. The individuals with 677TT genotype had significantly higher reduction of serum tHcy levels than individuals with the 677CC or 677CT genotypes. Although the individuals of Group 1 had significantly greater increase of their serum folate levels than those of Group 2, the reduction of serum tHcy concentrations between the two groups did not differ significantly. The individuals with 677CT genotype had statistically significant greater reduction of serum tHcy levels when received folinic acid than methylfolate supplementation. Conclusions: The tHcy-lowering treatment which included FNA supplementation compared to treatment which included L-methylfolate supplementation caused a greater increase of serum folate levels but no difference in reduction of serum tHcy levels. The reduction of serum tHcy levels was influenced by the existence of MTHFR C677T and not A1298C gene polymorphisms. The individuals with 677CT genotype appear to benefit more by the treatment which included FNA than L-methylfolate supplementation.

Vitamin B12 Status in Recreational Users of Nitrous Oxide: A Systematic Review Focusing on the Prevalence of Laboratory Abnormalities.

The recreational use of nitrous oxide (N2O) as "laughing gas" is a growing problem. The chronic toxicity of N2O is mainly due to its ability to oxidize vitamin B12, making it dysfunctional as a cofactor in metabolic pathways. This mechanism plays a major role in the development of neurological disorders in N2O users. The assessment of vitamin B12 status in N2O users is important but challenging due to the lack of decrease in total vitamin B12 in most cases despite genuine vitamin B12 functional deficiency. Other biomarkers, such as holotranscobalamin (holoTC), homocysteine (tHcy) and methylmalonic acid (MMA), are interesting candidates to properly assess vitamin B12 status. Here, we conducted a systematic review of case series in order to assess the prevalence of abnormal values of total vitamin B12, holoTC, tHcy and MMA in recreational N2O users, which is an important prerequisite for determining the best screening strategy in future guidelines. We included 23 case series (574 N2O users) from the PubMed database. Total circulating vitamin B12 concentration was low in 42.2% (95% confidence interval 37.8-46.6%, n = 486) of N2O users, while 28.6% (7.5-49.6%, n = 21) of N2O users had low circulating concentrations of holoTC. tHcy levels were elevated in 79.7% (75.9-83.5%, n = 429) of N2O users, while 79.6% (71.5-87.7%, n = 98) of N2O users had increased concentrations of MMA. In summary, the increases in tHcy and MMA were the most prevalent abnormalities, and should be measured alone or in combination in symptomatic N2O users rather than total vitamin B12 or holoTC.

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.

Methylenetetrahydrofolate reductase polymorphisms and elevated plasma homocysteine levels in small vessel disease.

Despite its public health importance, the causes of small vessel disease (SVD) are not fully understood. The presence of SVD in monogenic twins indicates the involvement of genetic factors in the pathogenesis of this disease. The purpose of this study was to investigate the association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with SVD risk. Patients with SVD and matched controls were recruited from Tianjin Union Medical Center and Tianjin Huanhu Hospital. Clinical and laboratory data were collected. Plasma total homocysteine (tHcy) and folate levels were measured, and MTHFR rs1801133 (C677T) and rs1801131 (A1298C) single-nucleotide polymorphisms were genotyped. We analyzed potential associations among SVD and MTHFR polymorphisms, tHcy, and folate levels. Patients with SVD displayed significantly decreased plasma folate levels (Z=-3.537, p<.001) and increased tHcy levels (Z=4.910, p<.001) compared with controls. Significantly different plasma tHcy levels were associated with rs1801133 (χ2 =6.664, p=.036), and post hoc analysis indicated higher plasma tHcy levels in individuals carrying the TT allele compared with levels in those carrying the TC allele (Z=2.478, p=.013). No significant differences in tHcy levels were observed for rs1801131 alleles. The genotype and allele frequencies of rs1801133 were different between SVD and control groups (χ2 =9.378, p=.009). There was no significant difference in distributions of rs1801131 genotypes between the two groups, and multivariable logistic regression analysis showed that rs1801131 and rs1801133 were not significantly associated with the risk of SVD. Our study indicates that an elevated plasma tHcy level is independently associated with the development of SVD. Although MTHFR rs1801133 is linked to increased plasma homocysteine (Hcy) levels, it is not a risk factor for SVD. rs1801131 is not related to Hcy levels or SVD risk.

Morphological and Functional Remodeling of the Ischemic Heart Correlates with Homocysteine Levels.

Homocysteine (Hcy) is involved in various methylation processes, and its plasma level is increased in cardiac ischemia. Thus, we hypothesized that levels of homocysteine correlate with the morphological and functional remodeling of ischemic hearts. Thus, we aimed to measure the Hcy levels in the plasma and pericardial fluid (PF) and correlate them with morphological and functional changes in the ischemic hearts of humans. Concentration of total homocysteine (tHcy) and cardiac troponin-I (cTn-I) of plasma and PF were measured in patients undergoing coronary artery bypass graft (CABG) surgery (n = 14). Left-ventricular (LV) end-diastolic diameter (LVED), LV end-systolic diameter (LVES), right atrial, left atrial (LA) area, thickness of interventricular septum (IVS) and posterior wall, LV ejection fraction (LVEF), and right ventricular outflow tract end-diastolic area (RVOT EDA) of CABG and non-cardiac patients (NCP; n = 10) were determined by echocardiography, and LV mass was calculated (cLVM). Positive correlations were found between Hcy levels of plasma and PF, tHcy levels and LVED, LVES and LA, and an inverse correlation was found between tHcy levels and LVEF. cLVM, IVS, and RVOT EDA were higher in CABG with elevated tHcy (>12 µM/L) compared to NCP. In addition, we found a higher cTn-I level in the PF compared to the plasma of CABG patients (0.08 ± 0.02 vs. 0.01 ± 0.003 ng/mL, p < 0.001), which was ~10 fold higher than the normal level. We propose that homocysteine is an important cardiac biomarker and may have an important role in the development of cardiac remodeling and dysfunction in chronic myocardial ischemia in humans.

Abstract WP174: Elevated Homocysteine Intensify The Effect Of Lipoprotein(a) On Stroke Recurrence

Introduction: Lipoprotein(a) [Lp(a)] and homocysteine (tHcy) are risk factors for ischemic stroke. tHcy show great impact on Lp(a) binding to fibrin and interaction between Lp(a) and Mac-1 integrin, which might intensify the atherogenic and thrombotic pathway mediated by Lp(a). The study aims to explore the effect of Lp(a) on stroke recurrence within 1 year in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA), based on different tHcy level. Method: A total of 10068 patients with AIS or TIA from the third China National Stroke Registry cohort were included. Since Lp(a) levels vary strongly between ethnicities, the cut-off value was set at the 80 th percentile based on National Lipid Association recommendation. The association between Lp(a) and stroke recurrence was evaluated using Cox proportional hazards model. Patients were further categorized to five different subtypes according to the TOAST criteria. The interaction between Lp(a) and tHcy was tested in different subtypes. Result: 8054 patients were classified into the ≤80 th group, 2014 patients were classified into the &gt;80 th group. No significant differences were found between the two groups in terms of age, sex, and traditional risk factors (P&gt;0.05). 999 patients experienced recurrent stroke in 1 year follow-up. Patients with Lp(a)&gt;80 th patients had a higher risk of stroke recurrence (11.57% vs 9.51%). Patients were further stratified by tHcy (&gt;15 and ≤15 μmol/L). Among all patients, the highest recurrence rate (12.8%) was observed in the patients with elevated both Lp(a) and tHcy (aHR 1.41; 95%CI 1.14-1.74), the interaction between Lp(a) and tHcy was observed (P=0.03). We also found significant interaction among large-artery atherosclerosis (LAA) subtype (P&lt;0.01). Conclusion: The finding indicated elevated tHcy might intensify Lp(a)-associated stroke recurrence. Elevated Lp(a) should receive more attention in AIS/TIA patients with elevated tHcy, especially in the LAA subtype.

Elevated levels of total homocysteine after ischemic stroke: a potential marker for in-hospital outcomes

ABSTRACT Objectives Our goal was to determine the risk conferred by elevated total homocysteine (tHcy) levels on recurrent stroke and cardiovascular disease (CVD) events after an ischemic stroke (IS), using data from the Chinese Stroke Center Alliance (CSCA). Methods The study consisted of 746,854 total participants with IS. Subjects were split into groups as well as quartiles according to tHcy level. Groups included a hyperhomocysteinemia (HHcy) group with tHcy ≥15 μmol/l and a normohomocysteinemia group (nHcy) with tHcy <15 μmol/l. The determined groups and quartiles underwent multiple logistic regression models with nHcy or quartile 1 as reference groups, respectively. The information from these analyses was adjusted for potential covariates and used to investigate the association between blood tHcy and in-hospital outcomes. Information collected at discharge included in-hospital stroke recurrence and CVD events. Results The mean [SD] age of participants was 66.2 [12.0] and 37.4% (n = 279,571) were female. The median hospital duration was 11.0 days (interquartile range, 8.0–14.0 days) and 343,346 (46.0%) patients were identified as HHcy cases (tHcy ≥15 μmol/). According to the tHcy quartile, the cumulative rates of stroke recurrence (from lowest quartile to highest) were 5.2%, 5.6%, 6.1%, and 6.6% (P < 0.0001). Similarly, those of CVD events were 5.8%, 6.1%, 6.7%, and 7.2% (P < 0.0001). Compared with the nHcy group, the HHcy group was associated with increased risks of in-hospital stroke recurrence (21912 [6.4%] vs. 22048 [5.5%], with the adjusted odds ratio (OR) 1.08, 95% CI: 1.05 to 1.10) as well as CVD events (24001 [7.0%] vs. 24236 [6.0%], with the adjusted OR: 1.08, 95% CI: 1.06 to 1.10) among patients with IS in the fully adjusted model. Conclusion HHcy was associated with increased in-hospital stroke recurrence and CVD events among patients with IS. In low-folate regions, tHcy levels may potentially predict in-hospital outcomes after IS.

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.

Associations of Serum Total Homocysteine Levels with Various Demographic, Clinical and Genetic Characteristics in Healthy Greek Adults.

The aim of this study was to investigate the association of serum total Hcy (tHcy) levels with various demographic, clinical and genetic characteristics in healthy Greek adults. Anthropometric characteristics (height, weight), systolic and diastolic blood pressure, complete blood count and biochemical assessments, were recorded and measured among 383 Greek adults (199 men). Serum folate, Cobalamin (Cbl) and tHcy levels were determined using immunoassays methods. The MTHFR C677T and A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. MTHFR C677T gene polymorphism, serum folate and Cbl levels were correlated with serum tHcy levels independently. The individuals with 677TT genotype had significantly higher serum tHcy levels than individuals with 677 CC or CT genotypes. Regarding the MTHFR C677T gene polymorphism, the existence of the T allele was associated with statistically significantly lower serum folate and higher serum tHcy levels than C allele. Regarding the MTHFR A1298C gene polymorphism, the existence of the C allele was associated with statistically significant lower serum tHcy levels than A allele. Furthermore, there was no significant correlation between the serum tHcy levels and demographic (except age) or clinical characteristics (sex, BMI, smoking status, SBP, DBP, HGB, HCT, TC, TG, HDL-C, LDL-C, TC/HDL-C). Serum tHcy levels are influenced by the existence of MTHFR C677T gene polymorphism (mainly 677TT genotype), serum folate and Cbl levels. Individuals with hyperhomocysteinemia should be further investigated for the existence of MTHFR C677T gene polymorphism, with the 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.

Homocysteine and methylmalonic acid in Phenylketonuria patients.

Hyperhomocysteinemia and vitamin B12 deficiency have been reported in patients with phenylketonuria. In this study, total homocysteine (tHcy) and methylmalonic acid (MMA) levels were analyzed in samples from 25 phenylketonuria (PKU) patients. Comparisons were made between pre- and post-treatment values (n= 3); on treatment values, between periods with high and normal/low phenylalanine (Phe) levels (n= 20); and in women before, during and after pregnancy (n= 3). THcy levels decreased after treating PKU with metabolic formula (p=0.014). Except for a pregnant woman before pregnancy, none of the patients had tHcy values above the normal range. In fact, tHcy was < 5 μmol/L in 34% of the samples. We observed a decrease in Phe, tHcy, and tyrosine levels during pregnancy. MMA levels did not differ significantly, with values remaining in the normal range. These data indicate that there was no B12 deficiency in patients who adhere to the diet. In conclusion, in PKU patients treated with metabolic formula, tHcy is frequently not elevated, remaining even in the lower normal range in some patients. Thus, clinical follow-up and adherence to dietary treatment are crucial to prevent B12 deficiency.

Nutritional and health status of adult Syrian refugees in the early years of asylum in Germany: a cross-sectional pilot study

BackgroundMigration is usually accompanied by changes in the social, cultural, and religious environment, socioeconomic status, and housing conditions, all of which affect nutritional health. In a cross-sectional study, we assessed the dietary intake as well as nutritional and health situation in a population of Syrian refugees who have resided in Germany for at least six months up to four years since 2015. The primary aim of this pilot study was to evaluate the nutritional and health status in comparison to reference values.MethodsBetween December 2018 and March 2020, 114 adult Syrian refugees were included in the study. The subjects filled out questionnaires on sociodemographic variables, exercise, and nutrition behavior (three-day nutrition record). After a fasting blood draw, the subjects were examined for anthropometric parameters (height, weight, body mass index, waist circumference, waist-hip ratio, and body composition via a bioelectrical impedance analyzer). Various blood markers including iron status, hematological parameters, Vitamin D status, lipid metabolism, glucose metabolism, and total homocysteine (tHcy) were measured.ResultsAbout half of the participants (71 male, 43 female) had lived in Germany for less than three years. Over 60% of men and 30% of women were overweight (BMI 25–30 kg/m2) or obese (BMI > 30 kg/m2), while 79% of men and 74% of women observed an elevated body fat mass. The evaluation of the three-day nutrition records revealed an unfavorable supply situation for numerous critical nutrients. More than half of the women (53.5%) had depleted iron stores (serum ferritin < 15 µg/l). The 25-OH-Vitamin D blood levels showed a high prevalence of Vitamin D insufficiency (25–49.9 nmol/l: 38% of men and 21% of women) and deficiency (< 25 nmol/l: 44% of men and 70% of women). 83% of men and 67% of women showed tHcy levels in plasma > 10 nmol/l. Fasting insulin levels and the HOMA-IR index indicate a risk for insulin resistance. Hyperlipidemia was prevalent, especially in males with 24% showing hypertriglyceridemia (> 150 mg/dl) and LDL-hypercholesterolemia (> 130 mg/dl).ConclusionsThe nutritional and health status of the cohort of Syrian refugees in Germany examined in this study is unsatisfactory, and many of the investigated refugees are at risk for developing cardiovascular disease and type 2 diabetes mellitus. Further studies are required to investigate the nutritional and health situation of refugees. This is obligatory to find ways to avoid malnutrition with all its associated health, sociodemographic, and economic consequences.

Methionine and total homocysteine in hypertensive patients with renal excretory dysfunction.

The role of the kidneys in the metabolism and homeostasis of sulfur-containing amino acids is great, so the levels of methionine (Met), total homocysteine (tHcy) and their ratios can be of diagnostic value in chronic kidney disease (CKD), in a course of the arterial hypertension (AH). The aim of the study was to evaluate the Met/tHcy ratio in hypertensive patients with CKD. We used blood plasma of 76 patients aged 40-75 years with AH and the excretory dysfunction of the kidneys; subgroups: 1 - with proteinuria (n=37); 2 - without proteinuria with glomerular filtration rate (GFR) < 90 ml/min/1.73 m2 (n=39) and comparison group 3 - patients with AH without renal excretory dysfunction (n=28). Significantly lower Met levels were in subgroup 1. THcy levels were higher in subgroups 1 and 2 than in group 3. The Met/tHcy ratio revealed differences in subgroups 1 and 2 vs group 3. No differences were found in Arg and Lys levels. Positive correlations of the Met/tHcy ratio with the number of erythrocytes, but not with the level of hemoglobin, were revealed. In the ROC analysis, the cut-off points for the Met/tHcy ratio compared to group 3 were 3.08 for subgroup 1 and 3.36 for subgroup 2. With the progression of CKD, there is an increase in the levels of tHcy in the blood, and a decrease in the content of Met. A decrease in GFR, especially in a case with proteinuria, is accompanied by a decrease in the level of Met. The Met/tHcy ratio above 3.36 can be considered as the minimum of the balance between these sulfur-containing amino acids contents in a blood necessary for hypertensive patients with CKD.

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.

Relationship between MMP-9 serum levels and tHcy levels and total imaging load and cognitive dysfunction

ObjectivesTo investigate the correlation and predictive value of serum matrix metalloproteinase-9 (MMP-9) level with cognitive dysfunction and total imaging load in patients with cerebral small vessel disease (CSVD). MethodsA total of 80 patients with CSVD who were admitted to the First Affiliated Hospital of Xinxiang Medical University between April 2019 and April 2020 were enrolled. All subjects underwent T1-weighted imaging (T1WI), T2WI, fluid-attenuated inversion recovery (FLAIR), diffusion weighted imaging (DWI), serum sample collection, and assessment of cognitive function at a specific time-point after admission. According to the results of the neuropsychological test, subjects were divided into cognitive dysfunction group (n=40) and normal cognitive function group (n=40). The total imaging load was estimated according to the neuroimaging findings. Serum MMP-9 level was measured by an enzyme-linked immunosorbent assay (ELISA) kit. Beside, serum MMP-9 level and total imaging load were compared between the two groups. ResultsSerum levels of MMP-9 and plasma total homocysteine (tHcy) were negatively correlated with cognitive function (P<0.05). Serum MMP-9 level was found as a significant factor for diagnosing cognitive impairment due to CSVD (area under the curve (AUC), 0.756; sensitivity and specificity were 97.5% and 75.0%, respectively). THcy level was also found as significant factor for diagnosing cognitive impairment due to CSVD (area under the curve (AUC), 0.727; sensitivity and specificity were 97.5% and 75.0%, respectively). ConclusionSerum MMP-9 level and tHcy level were significantly correlated with cognitive function in patients with CSVD. Serum MMP-9 level has a specific correlation with the total imaging load in patients with CSVD. It plays an important role in diagnosing cognitive impairment in patients with CSVD.

Gender difference in association between H-type hypertension and subcortical ischemic vascular disease.

BackgroundSubcortical ischemic vascular disease (SIVD) is a leading cause of vascular dementia. The present study tries to explore not only the gender-specific association between H-type hypertension and SIVD but also the indirect effects of H-type hypertension on cognition through the ischemic brain injury caused by SIVD.Materials and methodsA total of 601 SIVD patients were included, comprising 322 males and 279 females. H-type hypertension was defined as hypertension accompanied with elevated serum total homocysteine (tHcy) level. The imaging manifestations of ischemic brain injury caused by SIVD were also evaluated, including white matter lesions (WML), lacunar infarction (LI) and brain atrophy (BA). Gender-specific subgroup analyses in association between H-type hypertension and SIVD were conducted, followed by a structural equation model based evaluation of the gender-specific mediating effects of SIVD on the relationship between H-type hypertension and cognition.ResultsFor males, there was no noticeable difference in WML, LI and BA scores among control group, isolated hypertension group, isolated high tHcy group, and H-type hypertension group in most brain regions, but significant difference was found in all brain regions for females. Multiple regression analyses showed that H-type hypertension was significantly associated with WML, LI and BA for females, but not for males. For males, H-type hypertension mainly affected cognition through direct effect, while the H-type hypertension effect was mediated by ischemic brain injury caused by SIVD for females.ConclusionH-type hypertension was more closely related to SIVD for females than males, suggesting a gender-specific difference in association patterns between H-type hypertension and cognition.