Plasma Homocysteine Levels Research Articles

Bacteroides ovatus accelerates metformin-induced vitamin B12 deficiency in type 2 diabetes patients by accumulating cobalamin

Vitamin B12 (VB12) deficiency, which may lead to hematologic and neurologic symptoms, has been associated with metformin use, but the underlying mechanism is unclear. Here we report the B. ovatus as an effective VB12 catcher which was enriched in the type 2 diabetes patients suffered from VB12 deficiency after 3 to 6 months of metformin treatment. Colonization of B. ovatus increased the plasma levels of methylmalonic acid and homocysteine in high-fat diet (HFD)-fed mice treated with metformin, and compromised the efficacy of metformin against the HFD-induced metabolic disorders. Mechanistically, metformin increased the intracellular accumulation of VB12 in B. ovatus via btuB upregulation and promoted ATP production for energy-dependent translocation of VB12 transporters at the inner membrane, leading to an enhanced colonization of B. ovatus to compete for VB12 with hosts and subsequently an aggravated VB12 deficiency in the host. Our findings illustrate a previously unappreciated mechanism of metformin leads to host VB12 deficiency by acting directly on gut bacteria to increase their VB12 uptake and consumption, and suggest that inter-host-microbe competition for nutrients may broadly impact human health and drug safety.

Highly scalable design of 3D copper-doped graphene printed microfluidic chip for the electrochemical quantification of plasma homocysteine

Elevated levels of plasma homocysteine (Hcy) increase the risk of various diseases, but early diagnosis and monitoring can help prevent and treat such diseases. However, current diagnostic assays that quantify Hcy levels fail to detect more complex and rare proteins related to certain mutations, i.e., N-homocysteinylated proteins (N-Hcy-proteins), which are important for clinical decision-making. Therefore, the discrete diagnosis of Hcy in each mutated protein is in high demand. In this study, we design and fabricate a disposable microfluidic Hcy sensor chip (MHS-chip). Specifically, we utilize a laser direct-writing carbonization approach to mount a microfluidic channel filled with three-dimensional Cu-doped graphene and sensing electrodes onto a polyimide film for the first time. This microfluidic channel promotes the binding of N-Hcy-proteins and isolates the Hcy from a 10 µL plasma sample, while the sensing electrode is used for detection. The MHS-chip has a linear dynamic range of 0.01–124 µM and a detection limit of 2.9 nM, which is suitable for clinical application. Moreover, it exhibits good selectivity, high reproducibility, and real-time applicability in plasma samples. Overall, the MHS-chip is an efficient, low-cost device for the early diagnosis of Hcy and can be applied in point-of-care tests.

A case report of homocysteinuria with endophthalmitis and diabetes

Homocysteinuria is a rare inherited metabolic disorder that leads to the accumulation of homocysteine, which is toxic to blood vessels and other tissues. We present the case of a 29-year-old female with homocysteinuria and recently diagnosed diabetes mellitus presented with sudden eye symptoms and was diagnosed with endophthalmitis. High blood glucose levels were detected and further investigation revealed that the patient had a history of childhood vision difficulties and elevated plasma homocysteine levels. This case report highlights the importance of considering homocysteinuria in patients presenting with endophthalmitis in aphakic eyes and diabetes, and underscores the need for close monitoring of blood glucose levels and insulin therapy in patients with homocysteinuria and diabetes.

Association between Plasma Homocysteine Level and Atherogenic Index of Plasma among Hypothyroid Patients - A Case-Control Study

Introduction: Hypothyroidism is a common metabolic disorder in general population. Hypothyroidism is a commonly encountered health problem in Bangladesh and morbidity and mortality toll due to cardiovascular disease resulting from hypothyroidism is quite high. Hypothyroidism, dyslipidaemia and hyperhomocysteinemia are recognized risk factor for atherosclerosis and cardiovascular disease. Aim of the Study: The aim of this study was to evaluate the association between plasma Homocysteine level and atherogenic Index of plasma in patients with hypothyroidism. Methods: This was a case-control study and conducted in the Department of Biochemistry in cooperation with Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh during the period from January, 2012 to December, 2013. In our study, we included 60 newly diagnosed hypothyroid individuals as case and 60 euthyroid individuals as control. Result: In this study, most of the participants were female (62%) compared to male (38%) and we found the mean age of the case and control group was 34.31 ± 11.77 years and 32.42 ± 12.51 years. Mean serum homocysteine was found significantly higher in case group (19.00 ± 7.58 µmol/L) than control group (9.59 ± 1.91µmol/L).Mean AIP was found significantly higher in case (0.75 ± 0.27) than control (0.35 ± 0.20). We found 49 (81.67%) cases were within increased risk group of atherogenesis where as in control group it was 28 (46.67%).In present study, mild hyperhomocysteinemia was found in 80% cases and moderate hyperhomocysteinemia in 13.3% cases where as in control group it was 10% & 0% respectively. Conclusion: In this study, we found that total plasma homocysteine level was significantly increased in recently diagnosed hypothyroidism and was normal in control groups. We also found that hypothyroidism is associated with high atherogenic index and hyperhomocysteinemia which causes premature atherosclerosis.

A Methionine-Portioning-Based Medical Nutrition Therapy with Relaxed Fruit and Vegetable Consumption in Patients with Pyridoxine-Nonresponsive Cystathionine-β-Synthase Deficiency.

The main treatment for pyridoxine-nonresponsive cystathionine-β-synthase deficiency is a strict diet. Most centers prescribe low-protein diets based on gram-protein exchanges, and all protein sources are weighed. The purpose of this study is to investigate the effects of a more liberal methionine (Met)-based diet with relaxed consumption of fruits and vegetables on metabolic outcomes and dietary adherence. Ten patients previously on a low-protein diet based on a gram-protein exchange list were enrolled. The natural protein exchange lists were switched to a "Met portion exchange list". Foods containing less than 0.005 g methionine per 100 g of the food were accepted as exchange-free foods. The switch to Met portioning had no adverse effects on the control of plasma homocysteine levels in terms of metabolic outcomes. It resulted in a significant reduction in patients' daily betaine dose. All patients preferred to continue with this modality. In conclusion, methionine-portion-based medical nutrition therapy with relaxed consumption of fruits and vegetables seems to be a good and safe option to achieve good metabolic outcomes and high treatment adherence.

Maternal Plasma Homocysteine Levels & Pregnancy Outcome

Background: Elevated homocysteine levels have been implicated in various adverse pregnancy outcomes, but its association with high-risk pregnancies remains inadequately explored. This study examines the relationship between maternal plasma homocysteine levels and socio-demographic, lifestyle characteristics in high-risk versus control pregnancy groups.  Methods: A comparative cohort study design was utilized, involving 108 participants divided into a control group (n=44) with normal pregnancies and a study group (n=64) identified as high-risk. The study assessed maternal plasma homocysteine levels using a chemiluminescent method and evaluated socio-demographic and lifestyle characteristics through comprehensive history intake and examinations. Statistical analyses compared homocysteine levels between groups and within specific conditions in the high-risk group.  Results: The study group demonstrated a higher mean age and significant percentages of unbooked pregnancies, illiteracy, unemployment, and rural residency compared to the control group. Notably, approximately two-thirds of the high-risk group had a diet deficient in essential nutrients. Homocysteine levels were significantly elevated in the high-risk group (mean 12.82 ± 2.46 μmol/L) compared to the control group (mean 6.4 ± 1.16 μmol/L, P < 0.05). Within the high-risk group, specific conditions such as previous abortions, preterm pain, and antepartum hemorrhage were associated with distinct homocysteine level patterns, suggesting varying degrees of risk across different pregnancy complications.  Conclusion: Elevated homocysteine levels are significantly associated with high-risk pregnancies and specific adverse outcomes. The findings highlight the importance of addressing socio-demographic and lifestyle factors alongside biochemical markers in the management and intervention strategies for high-risk pregnancies. Tailored nutritional and lifestyle interventions targeting homocysteine levels could potentially mitigate these risks.

Plasma homocysteine levels and associated factors in community-dwelling adolescents: the EVA-TYROL study.

Homocysteine (Hcy) has been associated with an adverse cardiovascular risk profile in adolescents. Assessment of the association between plasma Hcy levels and clinical/laboratory factors might improve our understanding of the pathogenesis of cardiovascular disease. Hcy was measured in 1,900 14- to 19-year-old participants of prospective population-based EVA-TYROL Study (44.3% males, mean age 16.4 years) between 2015 and 2018. Factors associated with Hcy were assessed by physical examination, standardized interviews, and fasting blood analysis. Mean plasma Hcy was 11.3 ± 4.5 µmol/L. Distribution of Hcy was characterized by extreme right skew. Males exhibited higher Hcy and sex differences increased with increasing age. Univariate associations with Hcy emerged for age, sex, body mass index, high-density lipoprotein cholesterol, and for factors pertaining to blood pressure, glucose metabolism, renal function, and diet quality, whereas the most important multivariate predictors of Hcy were sex and creatinine. Clinical and laboratory factors associated with Hcy in adolescents were manifold, with sex and high creatinine identified as strongest independent determinants. These results may aid when interpreting future studies investigating the vascular risk of homocysteine.

In Situ Fluorescence Imaging Reveals Contribution of Cerebral Hydroxyl Radicals in Hyperhomocysteinemia-Induced Alzheimer-like Dementia.

Elevated plasma level of homocysteine, also termed as hyperhomocysteinemia, is acknowledged as a significant and independent risk factor of Alzheimer's disease. However, the mechanistic insight has not been thoroughly elucidated yet. In this work, 3,5-dihydroxybenzyloxy was explored as the unique reaction trigger and integrated into the naphthalimide fluorophore via a carbamate linker to afford a new probe for •OH imaging. •OH treatment induced aromatic hydroxylation and subsequent elimination reaction to release the caged fluorophore, accompanied with a highly specific and sensitive turn-on fluorescence response. Cell imaging results revealed that excess homocysteine triggered overwhelming •OH production, which was mediated by N-methyl-d-aspartate receptor and NADPH oxidase, and the resultant •OH stress further initiated neuronal ferroptosis, also confirmed by western blot analyses. Additionally, hyperhomocysteinemic mouse models were established, and Alzheimer-like dementia of the mice was observed from behavioral tests. Most importantly, with this probe, cerebral •OH fluctuation was in situ visualized in live mice, which positively correlated with the severity of Alzheimer-like dementia induced by hyperhomocysteinemia. These results reveal that cerebral •OH stress may be the critical nexus linking hyperhomocysteinemia and Alzheimer's disease. This work provides a robust fluorescence probe for in situ visualizing the cerebral •OH fluctuations and illuminating critical insights into •OH contributions in brain disorders.

H-type hypertension is a risk factor for chronic total coronary artery occlusion: a cross-sectional study from southwest China

BackgroundChronic total coronary occlusion (CTO) is serious and the "last bastion" of percutaneous coronary intervention. Hypertension and hyperhomocysteinemia (HHCY) are synergistic and significantly increase cardiovascular event risk. The relationship between H-type hypertension and CTO remains unclear; thus, this cross-sectional study investigated this potential association.MethodsBetween January 2018 and June 2022, 1446 individuals from southwest China were recruited to participate in this study. CTO was defined as complete coronary artery occlusion persisting for over three months. H-type hypertension was defined as hypertension with plasma homocysteine levels ≥ 15 µmol/L. Multivariate logistic regression models were applied to assess the association between H-type hypertension and CTO. Receiver operating characteristic (ROC) curves were generated to determine the accuracy of H-type hypertension in predicting CTO.ResultsOf the 1446 individuals, 397 had CTO, and 545 had H-type hypertension. After multivariate adjustment, the odds ratio (OR) for CTO in individuals with H-type hypertension was 2.3-fold higher (95% CI 1.01–5.26) than that in healthy controls. The risk of CTO is higher in individuals with H-type hypertension than in those with isolated HHCY and hypertension. The area under the ROC curve for CTO was 0.685 (95% CI, 0.653–0.717) for H-type hypertension.ConclusionsIn southwest China, H-type hypertension is significantly related to the occurrence of CTO.Trial registrationThis retrospective study was registered with the Chinese Clinical Trials Registry (http://www.chictr.org.cn, ChiCTR2100050519.2.2).

Effect of plasma homocysteine levels on methylation and expression of thrombomodulin gene in patients with retinal vein occlusion

Objective: To explore the effect of plasma homocysteine (Hcy) levels on methylation and expression of thrombomodulin (TM) gene in patients with retinal vein occlusion (RVO).Methods: 11 cases of patients who were diagnosed as RVO in Department of Ophthalmology in Baogang Hospital from January 2019 to December 2020 were included in this research. 11 cases of healthy people who came to our physical examination center for physical examination during the same period were included into the control group. Fasting cubital venous blood was collected in the morning, plasma Hcy levels were measured by means of enzyme cycle assay, TM gene methylation was detected by methylation-specificity polymerase chain reaction (MSP), and the correlation between characteristic changes in plasma Hcy and TM gene methylation was analyzed in the research subjects.Results: Plasma Hcy expression levels were higher in the RVO group than those in the control group (p < .01). In the control group, the TM primer set region was basically unmethylated, while in the RVO group, the TM primer set region was partially methylated.Conclusions: Plasma Hcy affects the occurrence and development of RVO through methylation of TM encoding gene.

Raised Maternal Homocysteine Levels in Antenatal Women at 10 to 14 Weeks of Gestation and Placenta-Mediated Complications: A Cohort Study.

Background Placenta-mediated complications, such as preeclampsia, placental abruption, and fetal growth restriction, can indeed lead to significant maternal and perinatal morbidity and mortality. Early detection and management of these conditions are crucial to ensuring optimal outcomes for both the mother and baby.However, there have been inconsistent correlations found between maternal homocysteine levels and placenta-related problems in various studies. Therefore, prospective research based on data pointing to a role for hyperhomocysteinemia in placenta-mediated complications will open doors for early detection and management of these complications. Thus, this study aims to determine if a higher risk of placenta-mediated problems is connected with a higher maternal plasma homocysteine content between 10 and 14 weeks of gestation. Methodology An observational prospective cohort study was conducted in the Department of Obstetrics and Gynecology, consisting of all the antenatal women between 10 and 14 weeks of gestation attending outpatient departments or inpatients admitted in labor rooms or wards having singleton pregnancies. Along with socio-demographic information and detailed history, a clinical examination was performed, and blood samples were collected to determine plasma homocysteine levels. Results As per thereceiver operating characteristic curve (ROC curve), the cut-off value taken was <5 for the low level of serum homocysteine, 5 to 15 micromol/L for the normal value, and >15 micromol/L for a raised serum homocysteine level. The cutoff value for our study was 45 micromol/L with a sensitivity of 78.33%, a specificity of 91.67%, a positive predictive value of 90.38%, and a negative predictive value of 80.88% with a diagnostic accuracy of 85%. This means that, for most of the women included in the present study, those who developed placenta-mediated complications had serum blood homocysteine levels of 45 micromol/L or more at 10-14 weeks of gestation. Conclusion Women with high homocysteine levels in the late first trimester had more placenta-mediated complications, such as abruption, pre-eclampsia, restricted fetal growth, and recurrent pregnancy losses, compared to women with a normal level of homocysteine in the late first trimester. Therefore, measuring blood homocysteine levels in pregnancy may be helpful as a diagnostic test for the early detection of high-risk individuals for placenta-mediated complications.

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.

Homocysteine promotes atherosclerosis through macrophage pyroptosis via endoplasmic reticulum stress and calcium disorder

BackgroundElevated plasma homocysteine levels, known as hyperhomocysteinemia, have been identified as an independent risk factor for atherosclerosis and related cardiovascular diseases. Macrophage pyroptosis-mediated inflammation is crucial in the development of atherosclerosis, but the underlying mechanisms remain unclear.MethodsA hyperhomocysteinemia atherosclerotic model with ApoE−/− mice fed with a high-methionine diet was constructed to investigate the role of plasma homocysteine in atherosclerosis. THP-1-derived macrophages were used to investigate the mechanisms by which Hcy regulates pyroptosis.ResultsWe found that hyperhomocysteinemia resulted in larger atherosclerotic plaques and more secretion of inflammatory cytokines, while these effects were attenuated in Caspase-1 knockdown mice. Likewise, in vitro experiments demonstrated that treatment of macrophages with homocysteine resulted in NLRP3 inflammasome activation and pyroptosis, as evidenced by cleavage of Caspase-1, production of downstream IL-1β, elevation of lactate dehydrogenase activity, and extensive propidium iodide-positive staining of cells. These were all inhibited by Caspase-1 inhibitor. In addition, excessive generation of reactive oxygen species was associated with mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential and ATP synthesis. Moreover, further experiments revealed that homocysteine induced endoplasmic reticulum stress, enhanced communication between the endoplasmic reticulum and mitochondria, and consequently contributed to calcium disorder. Furthermore, the endoplasmic reticulum stress inhibitor, 4PBA, the calcium chelator, BAPTA, and calcium channel inhibitor, 2-APB significantly improved macrophage pyroptosis.ConclusionHomocysteine accelerates atherosclerosis progression by enhancing macrophages pyroptosis via promoting endoplasmic reticulum stress, endoplasmic reticulum-mitochondria coupling, and disturbing of calcium disorder.

Homocysteine altered gyrification related to self‐awareness of everyday cognition

AbstractBackgroundPrevious studies on homocysteine have verified higher homocysteine may adversely influence cognition performance in individuals with subjective cognitive decline (SCD), whereas the potential mechanisms for this relationship are still unclear.MethodWe analyzed data from 23 individuals with SCD enrolled in the 500 nm light therapy cohort who filled the 12 items Everyday Cognition scale (ECog‐12) and had plasma homocysteine levels assessed at the time of their baseline 3T MRI scans. Gyrification and cortical thickness were obtained by using whole brain region of interest (ROI)‐based approach with the CAT12 toolbox (in SPM12). Statistical analyses used one‐sample t‐test including age and sex as covariates. Regions of significant group effects were used as regions of interest for cognitive performance analyses.ResultAt corrected thresholds (p &lt; 0.05, Holm‐Bonferroni‐corrected), there were significant negative correlations between homocysteine and gyrification in the left temporal pole (p = 0.012000) and right inferior temporal sulcus (p = 0.012268). For cortical thickness, we found a significant positive correlation of homocysteine and cortical thickness in the right inferior temporal sulcus (p = 0.032744). In addition, a significant positive correlation was found between the self‐report ECog‐12 scores and gyrification of the left temporal pole.ConclusionHomocysteine alters local surface shape in temporal lobule in SCD patients and localized low gyrification may imply impaired self‐awareness of everyday cognition.

Evaluation of relationship between hyperuricemia and hyperhomocysteinemia

Aims: Hyperuricemia is generally a subclinical disorder. Uric acid takes part in the malignities, obesity-insulin resistance syndrome, and some other cardiovasculer problems. Plasma homocysteine (Hcy) levels are one of the major risk factors of coronary heart disease, one of the major reasons of adult mortality. In this study, it was aimed to determine relationship between hyperuricemia and hyperhomocysteinemia. Methods: In this prospective research, 32 patients and 32 healthy controls were investigated. The age, sex, height, weight, complaints, medications and arterial blood pressure of the patients were measured and recorded. Moreover, whole blood test, fasting plasma glucose, serum lipids, sedimentation, cobalamin, folate, plasma total Hcy and uric acid levels were determined. Results: In the patient group 62.51% was male and 37.5% was female. The mean age was 54.69+12.03. In the healthy controls 62.5% was male and 37.5% was female, and the mean age was 51.59+9.57. The difference between the mean ages of both groups was not significant (p&gt;0.05). Uric acid levels were found to be 8.61±0.98 mg/dl in the patient group and 4.09±0.99 mg/dl in the control group, and this difference was significant (p&lt;0.001). Hcy levels were found to be 10.99+1.42 µmol/L in the patient group and 6.67±0.80 gmoI/L in the control group. This difference was also statistically significant (p&lt;0.001) Conclusion: Hyperuricemia which is generally a subclinical disorder is accepted a coronary risk factor with the presence of other risks. Elevated plasma homocysteine is an independent risk factor for coronary heart disease. There are similar features of the both etiologia. Therefore we recommend to calculate the plasma homocysteine levels in hyperuricemic patients who have the risk of coronary heart disease and to treat the hyperuricemic patients having hyperhomocysteinemia and coronary risk factors.

Impact of Lisinopril on Cardiometabolic Risk Factors in Sisters of Women With Polycystic Ovary Syndrome.

Women with polycystic ovary syndrome (PCOS), the most common endocrinopathy in reproductive age, are characterized by increased cardiometabolic risk. Similar hormonal and metabolic changes were found in their siblings. The purpose of our study was to compare blood pressure-lowering and pleiotropic effects of lisinopril between sisters of women with PCOS and their unrelated peers. The study included two age-, body mass index-, and blood pressure-matched groups of women with grade 1 hypertension: 26 sisters of PCOS probands (Group 1) and 26 individuals without a family history of PCOS (Group 2), receiving 10-40 mg of lisinopril daily. Blood pressure, glucose homeostasis markers, plasma levels of lipids (androgens, estradiol, high-sensitivity C-reactive protein (hsCRP), homocysteine, fibrinogen, and uric acid), and urinary albumin-to-creatinine ratio (UACR) were measured before lisinopril treatment and 6 months later. At baseline, the study groups differed in insulin sensitivity, testosterone, free androgen index (FAI), hsCRP, homocysteine, and UACR. Blood pressure-lowering properties of lisinopril did not differ between the groups. The decrease in homocysteine and UACR, although observed in both groups, was stronger in Group 2 than in Group 1. Only in women without a family history of PCOS lisinopril improved insulin sensitivity and reduce hsCRP, fibrinogen, and uric acid. The remaining markers did not change throughout the study. Cardiometabolic effects of lisinopril correlated with testosterone, free androgen index, and changes in insulin sensitivity. The obtained results suggest that cardiometabolic effects of lisinopril may be slightly less pronounced in sisters of women with PCOS than in women without a family history of this disorder.

Homocysteine levels, H-Hypertension, and the MTHFR C677T genotypes: A complex interaction

Background and objectivesHigh homocysteine levels are associated with increased risk of hypertension and stroke. Homocysteine is metabolized by the methylenetetrahydrofolate reductase (MTHFR). We aimed to investigate the levels of homocysteine and their association with hypertension, stroke, and antihypertensive medication usage in patients with different MTHFR C677T genotypes. Methods and resultsGenotype frequency of MTHFR polymorphism was performed, and plasma homocysteine levels were measured in 2,640 adult Lebanese patients. Hypertension, history of stroke, and list of medications were documented, among other clinical and demographic parameters. The TT mutant genotype and the T mutant allele of MTHFR were more prevalent in hyperhomocysteinemia (HHcy) and H-hypertensive (H-HTN, defined as hypertension with hyperhomocysteinemia) patients when compared to non-HHcy subjects and non H-HTN patients respectively. Homocysteine levels were significantly higher in hypertensive patients specifically among those on diuretics. A higher level of homocysteine was found in hypertensive patients with the MTHFR T allele compared to patients carrying the C allele. Among the T allele carriers, the average plasma homocysteine level was 13.3 ± 0.193 μmol/L for hypertensive subjects compared to 11.9 ± 0.173 μmol/L (non-hypertensives). Furthermore, homocysteine levels significantly correlated with stroke risk in patients with the T alleles. ConclusionsWe found an association of homocysteine with hypertension, hypertensive medication, and stroke risk among patients with the MTHFR T allele and the TT genotype. The association of diuretics therapy with higher homocysteine levels calls for routine measurements and therapeutic control of homocysteine in patients on diuretic, to improve health-related outcomes.

A RARE TREATABLE CAUSE OF ADULT ONSET SPASTIC PARAPARESIS

pastic paraparesis refers to weakness and stiffness of both lower limbs caused by lesions affecting the Pyramidal tract. It could be due to genetic or acquired etiology. Genetic causes include leukodystophies, Heriditary Spastic Paraplegia (HSP), metabolic disorders etc,. Acquired causes include B12 and folate deficiency , infections like HTLV-1 virus, HIV, neurosyphilis , vascular malformations and so on. Here we encounter a rare treatable cause of spastic paraparesis. A 28 year old male born out of 3o Consanguinous parents with normal developmental history came with insidious onset slowly progressive spastic paraparesis for the past 4 years. Initially at onset he noticed difficulty in getting up from squatting position, which was associated with stiffness of lower limbs. Then he noticed there was slippage of slippers while walking and he was aware about it. Physical examination revealed marfanoid Habitus ,increased tone and exaggerated reflexes involving both lower limbs .Motor power was MRC Grade 4/5 in both lower limbs in both proximal and distal muscles. Ocular Examination revealed Ectopia Lentis. MRI Spine screening was normal. MRI Brain revealed symmetric T2/FLAIR hyperintensities involving periventricular and deep white matter of bilateral frontoparietal region. Possibilities of Primary demyelinating diseases and genetic/degenerative leukoencephalopathies were considered. CSF examination was normal and oligoclonal bands were absent. Clinical Exome sequence testing was done in suspicion of Adult onset leukodystrophy which showed Homozygous MTHFR gene mutation on exon4. Plasma Homocysteine levels were elevated ( 60 µmol/L).Patient was started on Oral Vitamin B12 1500mcg/day, Folic acid and pyridoxine supplementation. Patient showed symptomatic improvement and is under follow up. MTHFR deficiency in adults is a mimicker of leukodystrophies and other white matter disease. It is a potentially treatable disease. Before considering degenerative diseases like HSP, treatable diseases should be considered.

Fifteen-year clinical prognosis and cardiovascular or limb event associated with homocysteine levels in peripheral arterial disease

BackgroundThere are limited reports on the relationship between plasma homocysteine (Hcy) levels and long-term all-cause death (ACD), cardiovascular events, or limb events in patients with peripheral arterial disease (PAD). We examined the relationship between plasma Hcy levels and 15-year these events in PAD patients. MethodsWe performed a prospective cohort study in 955 PAD patients. The patients were divided into four groups based on plasma Hcy levels with median (interquartile range). The endpoints were cumulative incidences of ACD, major adverse cardiovascular events (MACE), and MACE plus limb events (MACLE). ResultsThe incidences of ACD, MACE, and MACLE were correlated with plasma Hcy levels (P < 0.05). In multiple regression analysis, plasma Hcy had positive correlations with C-reactive protein (CRP), men, and critical limb ischemia (CLI) and negative correlations with estimated glomerular filtration rate (eGFR) and high-density lipoprotein cholesterol (p < 0.05). In Cox multivariate analysis, higher Hcy (HR 1.614, 95 % CI 1.229–2.119, p = 0.001), age, CRP, brain natriuretic peptide (BNP), D-dimer, lower body mass index, ankle brachial pressure index (ABI), serum albumin, eGFR, CLI, coronary heart disease (CHD), cerebrovascular disease, and diabetes were related to ACD; higher Hcy (HR 1.242, 95 % CI 1.004–1.535, p = 0.045), age, BNP, lower ABI, serum albumin, diabetes, and CHD were related to MACE; and higher Hcy (HR 1.290, 95 % CI 1.057–1.574, p = 0.012), BNP, lower ABI, serum albumin, CHD, and diabetes were related to MACLE (P < 0.05). Statins improved ACD, MACE, and MACLE (p < 0.01). ConclusionsPlasma Hcy was a risk factor for 15-year ACD, MACE, and MACLE in patients with PAD.

Polymorphism studying of the Angiotensin-converting gene for a group of patients with myocardial infarction in Saladin Governorate

Blood samples were collected from 120 people, including 70 people affected by Myocardial Infarction (MI) and 50 healthy people aged between 40 - 70 years. Patients were diagnosed by basis of clinical symptoms and after made laboratory tests in addition to electricity cardio Gram (ECG) by specialists. Also it is measured The concentration of homocysteine for both of groups, where its concentration Patient groups was (45.26 ± 0.71) μmol / L compared to the healthy group (7.86 ± 1) μmol / L. There was a significant difference obviously at level (0.01 and 0.05) between the two groups beside, a mutation Ins / Del was found. Using PCR technique, where appeared three genotypes (II, ID and DD), there was a clear difference in the value of the Allele frequency for Allele D in patients group compared to healthy, where was in patients group(0.664) while in healthy group (0.37). On the contrary, value of the Allele frequency has decreased for Allele I to patients where was(0.336) compared with healthy(0.63) This indicates the association of the deletion mutation (D) with MI and heights level of concentration Homocysteine in plasma. After analysis of Chi square 2, the resent studying proved that society of patients applies Hardy-Weinberg law for balance on it at a significant level (0.01) and Hardy-Weinberg law (p2 + 2pq + q2 = 1) where value of Chi square (7.61)which was less than its tabular value at a significant level (0.01) (9.21). As for the healthy society, it was a balance and applied Hardy-Weinberg law on it at a significant level (0.01) and (0.05) where value of Chi square (5.867) which was smaller than its tabular value at tow levels (9.21) and (5.99).