High Blood Homocysteine Level Research Articles

Elevated blood homocysteine increases the risk of incident Motoric Cognitive Risk syndrome: A two cohort study.

Motoric Cognitive Risk (MCR) syndrome, a pre-dementia syndrome characterized by cognitive complaints and slow gait, may have an underlying vascular etiology. Elevated blood levels of homocysteine, a known vascular risk factor, have been linked to physical and cognitive decline in older adults, though the relationship with MCR is unknown. We aimed to identify the association between homocysteine and MCR risk. We examined the association between baseline homocysteine levels and incident MCR using Cox proportional hazard models in 1,826 community-dwelling older adults (55% female) from two cohorts (Einstein Aging Study [EAS] and Quebec Longitudinal Study on Nutrition and Successful Aging [NuAge]). We calculated hazard ratios (HR) with 95% confidence intervals (CI), for each cohort as well as stratified by sex and vascular disease/risk factors. Median follow-up time was 2.2 years in EAS and 3.0 years in NuAge. Individuals with elevated baseline homocysteine levels (> 14 µmol/L) had a significantly higher risk of incident MCR compared to those with normal levels in NuAge (HR 1.41, 95% CI = 1.01-1.97, p = .04), after adjusting for covariates. Our exploratory stratified analyses found that these associations were significant only in men with vascular disease/risk factors. Higher blood homocysteine levels are associated with increased risk of developing MCR in older adults, particularly in men with vascular disease or vascular risk factors.

SYNERGISTIC EFFECT OF HIGH HOMOCYSTEINE AND LOW VITAMIN B12 LEVELS ON CARDIOVASCULAR AND STROKE RISK OF HYPERTENSIVE PATIENTS

Objective: Arterial hypertension is a risk factor for cardiovascular (CV) events, including stroke. High blood homocysteine levels (hyperhomocysteinemia) are also considered to increase CV risk and are associated with vitamin B12 deficiency that possibly increase CV and stroke risk, as well. The present study assessed the possible relation of high homocysteine and low vitamin B12 levels with the underlying CV and stroke risk of hypertensive patients. Design and method: This retrospective study comprised all hypertensives referred to our institutions and had a blood sample measurement of homocysteine and B12 (n = 32800). The 10-year fatal CV risk and stroke risk were calculated with the HeartScore and the FraminghamStrokeScore, respectively. The population was divided in quartiles according to homocysteine levels (groups 1, 2, 3 and 4 for increasing levels) and B12 levels (groups 1, 2, 3 and 4 for decreasing levels). Cardiovascular and stroke risk were calculated for each homocysteine and B12 quartile group as well as for each of the 16 homocysteine/B12 combination quartile subgroups. Results: The mean values for homocysteine were 13.3 ± 7.2 μmol/l and for B12 525 ± 196 pg/ml. For homocysteine quartiles 1, 2, 3, 4, CV risk was 3.4%, 5.5%, 9.0%, 17.9%, respectively (pfor trend 0.05). For B12 quartiles 1, 2, 3, 4, CV risk was 3.0%, 6.2%, 9.5%, 15.1%, respectively (pfor trend 0.01). Correlation coefficient ® between homocysteine and CV risk values was 0.416 (p < 0.0001) while between B12 and CV risk values was -0.369 (p < 0.0001). For homocysteine quartiles 1, 2, 3, 4, stroke risk was 4.2%, 7.3%, 12.9%, 25.0%, respectively (pfor trend 0.04). For B12 quartiles 1, 2, 3, 4, stroke risk was 5.4%, 9.2%, 13.4%, 19.3%, respectively (pfor trend 0.08). Correlation coefficient ® between homocysteine and stroke risk values was 0.474 (p < 0.0001) while between B12 and stroke risk values was -0.348 (p < 0.0001). The synergistic effect of increasing homocysteine and decreasing B12 values on CV and stroke risk increase is presented in Figure. Conclusions: High homocysteine levels and low vitamin B12 levels are individually and synergistically associated with the underlying CV and stroke risk of hypertensive individuals. Possible mechanisms merit further examination.

SYNERGISTIC EFFECT OF HIGH HOMOCYSTEINE AND LOW VITAMIN B12 LEVELS ON THE PREVALENCE OF ATRIAL FIBRILLATION IN HYPERTENSIVE PATIENTS

Objective: Atrial fibrillation (AF) is common arrhythmia in hypertensive patients. Besides hypertension, several other conditions are deemed to be associated with AF. High blood homocysteine levels (hyperhomocysteinemia) is a known risk factor for cardiovascular disease and are associated with vitamin B12 deficiency that possibly increase cardiovascular risk, as well. The present study assessed the possible effect of high homocysteine and low B12 levels on AF prevalence in hypertensive patients. Design and method: This retrospective study comprised all hypertensives referred to our institutions and had a blood sample measurement of homocysteine and B12 (n = 32800). The presence of sustained AF (SAF; Long-standing/Persistent or Permanent AF) was recorded with a resting electrocardiogram (ECG). Paroxysms of AF (PAF) were confirmed with previous relevant ECGs provided by the patient. The population was divided in quartiles according to homocysteine levels (groups 1, 2, 3 and 4 for increasing levels) and B12 levels (groups 1, 2, 3 and 4 for decreasing levels). The prevalence of AF (SAF and PAF) was calculated for each homocysteine and B12 quartile group as well as for each of the 16 homocysteine/B12 combination quartile subgroups. Results: The mean values for homocysteine were 13.3 ± 7.2 ?mol/l and for B12 525 ± 196 pg/ml. The prevalence of SAF, PAF and all-type AF (SAF and PAF) was 5.0%, 6.1% and 11.1%, respectively. For homocysteine quartiles 1, 2, 3, 4, SAF prevalence was 2.9%, 5.3%, 11.7%, 24.3% (pfor trend 0.049), PAF prevalence was 0.6%, 0.9%, 4.6%, 14.0% (pfor trend 0.090) and all-type AF prevalence was 3.2%, 5.4%, 11.5%, 22.2% (pfor trend 0.051), respectively. For B12 quartiles 1, 2, 3, 4, SAF prevalence was 2.9%, 6.4%, 11.0%, 20.2% (pfor trend 0.030), PAF prevalence was 2.5%, 5.1%, 7.7%, 9.0% (pfor trend 0.009) and all type-AF prevalence was 2.4%, 7.1%, 16.8% 21.0% (pfor trend 0.019), respectively. The synergistic effect of increasing homocysteine and decreasing B12 values on SAF, PAF and all-type AF prevalence is presented in Figure. Conclusions: High homocysteine levels and low vitamin B12 levels are individually and synergistically associated with the prevalence of AF in hypertensive individuals. Underlying mechanisms merit further examination.

Investıgatıon of The Effect of Serum Homocysteıne Level on Cognıtıve Functıons in Multıple Sclerosıs Patıents

Objective: In this study, we aimed to investigate whether serum homocysteine level was higher in patients with MS, and evaluate the effect of this situation on cognitive functions. In addition, we aimed to determine whether high blood homocysteine level is associated with socio-demographic and clinical features and determine the affected cognitive functions with neuropsychological tests.Methods: We looked at changes in the levels of vitamin B12 and folic acid associated with high levels of serum homocysteine levels. Cognitive performance, and laboratory values of 60 cases with Relapsing-remitting MS (RRMS) patient, and 30 healthy volunteers were compared. The frontal lobe activities, information processing speed, flexibility, and the ability of the calculation, as well as cognitive functions of attention and visuospatial perception and construction of complex skills were also evaluated. For these purposes, Paced Auditory Serial Addition Test (PASAT), Line Orientation Test (LOT) and Stroop Test were used.Results: Test performance for all of the test steps were found to be defective in MS group more than the control group subjects. In addition, all steps of the test performance were found to be impaired in both patients and healthy subjects with high levels of homocysteine(p<0.001).Conclusion: In this study visual memory processes, visual-spatial functions, construction skills, planning, programming and executive functions were found to be significantly deteriorated and the reaction time prolonged in RRMS patients with high levels of homocysteine compared with healthy control group

886Serum folate and risk of disabling dementia: Community-based nested case-control study

Abstract Background Folate regulates homocysteine metabolism and high blood homocysteine level has been associated with risk of dementia. Accordingly, serum folate is hypothesized to decrease the risk of dementia but epidemiological evidence, especially for Japanese, is scant. The aim of this study was to examine associations between serum folate and risk of disabling dementia within a Japanese cohort over 20 years of follow-up. Methods We performed an intracohort case-control study nested in a community-based cohort, the Circulatory Risk in Communities Study (CIRCS), involving 13934 Japanese individuals aged 40-84 years at the baseline period of 1984-2005. Serum folate was measured in 511 cases of incident disabling dementia, and in 1022 controls whose age (±1 years), sex, area, and baseline year were matched with the cases. The diagnosis of disabling dementia was performed by attending physicians under the National Long-Term Care Insurance System in Japan. Conditional odds ratios of disabling dementia according to quintiles of serum folate were calculated using conditional logistic regression models. Results Serum folate was inversely associated with risk of disabling dementia. The multivariate odds ratios (95% confidence intervals) were 0.62(0.43-0.88), 0.71(0.49-1.00), 0.63(0.43-0.91), and 0.51(0.34-0.76) for persons with the second, third, fourth, and highest quintiles of serum folate, respectively, compared with the lowest quintiles (P for trend = 0.19). Conclusions Low serum folate level was associated with increased risk of disabling dementia among Japanese. Key messages e Low folate intake may have an adverse effect on developing dementia.

Causal Effects of Homocysteine, Folate, and Cobalamin on Kidney Function: A Mendelian Randomization Study.

Blood homocysteine level and related vitamin levels are associated with various health outcomes. We aimed to assess causal effects of blood homocysteine, folate, and cobalamin on kidney function in the general population by performing Mendelian randomization (MR) analysis. Genetic instruments for blood homocysteine, folate, and cobalamin levels were introduced from a previous genome-wide association (GWAS) meta-analysis of European individuals. Summary-level MR analysis was performed for the estimated glomerular filtration rate (eGFR) from the CKDGen consortium GWAS that included 567,460 European ancestry individuals. For replication, allele-score-based MR was performed with an independent U.K. Biobank cohort of 337,138 individuals of white British ancestry. In summary-level MR for the CKDGen data, high genetically predicted homocysteine levels were significantly associated with low eGFR (per 1 standard deviation, beta for eGFR change −0.95 (−1.21, −0.69) %), supported by pleiotropy-robust MR sensitivity analysis. Genetically predicted high folate levels were significantly associated with high eGFR change (0.86 (0.30, 1.42) %); however, causal estimates from cobalamin were nonsignificant (−0.11 (−0.33, 0.11) %). In the U.K. Biobank data, the results were consistently identified. Therefore, a high blood homocysteine level causally decreases eGFR. Future trials with appropriate homocysteine-lowering interventions may be helpful for the primary prevention of kidney function impairment.

Synergistic Effect of Serum Homocysteine and Diabetes Mellitus on Brain Alterations.

Both elevated blood homocysteine and diabetes mellitus (DM) are related to cognitive impairments or dementia. A previous study also demonstrated that the association between homocysteine and cognitive decline was much stronger in individuals with DM than in those without DM. This study aimed to examine the interactive effect of blood homocysteine and DM on brain pathological changes including brain atrophy, amyloid-β and tau deposition, and small vessel disease (SVD) related to cognitive impairments. A total of 430 non-demented older adults underwent comprehensive clinical assessment, measurement of serum homocysteine level, [11C] Pittsburgh Compound B (PiB) PET, [18F] AV-1451 PET, and brain MRI. The interactive effect of homocysteine with the presence of DM on brain atrophy, especially in aging-related brain regions, was significant. Higher homocysteine concentration was associated with more prominent brain atrophy in individuals with DM, but not in those without DM. In contrast, interaction effect of homocysteine and DM was found neither on Alzheimer's disease (AD) pathologies, including amyloid-β and tau deposition, nor white matter hyperintensity volume as a measure of SVD. The present findings suggest that high blood homocysteine level and DM synergistically aggravate brain damage independently of AD and cerebrovascular disease. With regard to preventing dementia or cognitive decline in older adults, these results support the importance of strictly controlling blood glucose in individuals with hyperhomocysteinemia and lowering blood homocysteine level in those with DM.

Levels of Vitamins and Homocysteine in Older Adults with Alzheimer Disease or Mild Cognitive Impairment in Cuba.

INTRODUCTION Age-related cognitive disorders, including Alzheimer disease, are among the main causes of disability and dependence in older adults worldwide. High blood homocysteine levels (hyperhomocysteinemia) are a risk factor for diseases whose metabolism involves different B vitamins. Antioxidant vitamins provide a protective effect by mitigating oxidative stress generated by these diseases. Epidemiological studies have presented varying results on the relationships between blood levels of these vitamins and such cognitive disorders. OBJECTIVE Evaluate the association of vitamin and homocysteine levels with mild cognitive impairment and Alzheimer disease in a group of Cuban older adults. METHODS A cross-sectional study was conducted in Havana, Cuba, of 424 persons aged ≥65 years: 43 with Alzheimer disease, 131 with mild cognitive impairment, and 250 with no signs of cognitive impairment. Dementia was diagnosed using criteria of the International 10/66 Dementia Research Group and Diagnostic and Statistical Manual of Mental Disorders (DSM IV), and mild cognitive impairment was diagnosed using Petersen's criteria. Blood levels of vitamins (thiamine, B-2, folate, B-12, C and A) and homocysteine were measured by standard procedures. Analysis of variance for continuous variables and percentage comparison tests for dichotomous variables were used to compare groups. RESULTS Persons with Alzheimer disease presented signifi cantly lower levels of vitamins B-2, C and A than healthy participants (p <0.05). Homocysteine levels were signifi cantly higher in those with Alzheimer disease and mild cognitive impairment than in participants with no cognitive impairment (p <0.05). Statistically, levels of thiamine, folic acid, and vitamin B-12 were not signifi cantly different across groups. Compared with those without cognitive impairment, prevalence rates (PR) in the Alzheimer group were signifi cantly higher for hyperhomocysteinemia (PR = 3.26; 1.84-5.80) and defi - ciency of all B vitamins: thiamine (PR = 1.89; 1.04-3.43), B-2 (PR = 2.85; 1.54-5.26), folate (PR = 3.02; 1.53-5.95), B-12 (PR = 2.21; 1.17-4.19), vitamin C (PR = 3.88; 2.12-7.10) and A (PR = 5.47; 3.26-9.17). In mild cognitive impairment, prevalence rates were signifi cantly higher for hyperhomocysteinemia (PR = 1.42; 1.08-1.87), vitamin B-2 defi ciency (PR = 1.70; 1.24-2.32) and vitamin A defi - ciency (PR =1.88; 1.05-3.38). CONCLUSIONS Hyperhomocysteinemia and various vitamin defi ciencies are related to Alzheimer disease and mild cognitive impairment. Longitudinal studies are needed to further elucidate the relationship between different nutritional biomarkers and dementia. A better understanding of this relationship could provide a basis for therapeutic and preventive strategies. KEYWORDS Vitamins, homocysteine, geriatrics, Alzheimer disease, cognitive impairment, Cuba.

Hypermethylation of dihydrofolate reductase promoter increases the risk of hypertension in Chinese.

Background:DNA methylation was considered to play an important role in hypertension. However, the direct association between dihydrofolate reductase (DHFR) promoter methylation and hypertension remains unclear. We thus aimed to investigate the relationship between DNA methylation of DHFR promoter and hypertension.Materials and Methods:A total of 371 hypertensive patients (diastolic blood pressure ≥90 mmHg and/or systolic blood pressure ≥140 mmHg or a history of antihypertensive treatment) and 320 age- and sex-matched healthy controls from the Hypertension Management Information System in Nanshan Community Health Service Centers were included in this case–control study. Quantitative methylation-specific polymerase chain reaction was used to measure the level of DHFR promoter methylation, which was presented as the percentage of methylated reference (PMR). A multivariate logistic regression model was used to explore the risk of DHFR promoter methylation.Results:Our results indicated that the level of DHFR promoter methylation was higher in hypertensive patients (median PMR, 34.32%; interquartile range, 11.34–119.60) than in healthy controls (median PMR, 18.45%; interquartile range, 8.16–35.40) (P < 0.001). Multivariable analysis showed that the risk of DHFR promoter hypermethylation was significantly higher in hypertensive patients than in healthy controls (odds ratio = 3.94, 95% confidence interval = 2.56–6.02, P < 0.001). Furthermore, hypermethylation was positively associated with sex, high blood homocysteine levels, and alcohol drinking. In particular, the area under the receiver operating characteristic curve was 0.688 (0.585–0.668) for the male hypertensive patients, suggesting the potential diagnostic value of DHFR promoter methylation in male hypertension.Conclusion:Our results demonstrated that DHFR promoter hypermethylation is positively associated with the risk of hypertension in Chinese.

Maternal and cord blood homocysteine, vitamin B12, folate, and B-type natriuretic peptide levels at term for predicting congenital heart disease of the neonate: A case-control study

Objective: To investigate the effectiveness of the metabolic markers homocysteine, vitamin B12, folate, and B-type natriuretic peptide in maternal and cord blood for detecting congenital heart disease.Methods: Homocysteine, vitamin B12, folate, and B-type natriuretic peptide concentrations in maternal and cord blood samples at term were measured in the case (n = 42) and control (n = 43) groups with and without fetal congenital heart disease, respectively. Additionally, newborns with congenital heart disease were divided into two subgroups: those with (n = 30) and without (n = 8) 6-month infant survival. The case and control groups and case subgroups were compared with each other with respect to maternal age, gravidity, parity, gestational age at delivery, birth weight, maternal and cord blood levels of homocysteine, vitamin B12, folate, and B-type natriuretic peptide, and arterial cord blood pH and base excess values. Statistical analyses were performed using SPSS for Windows, version 22.0. The Student’s t-test, the Mann–Whitney U test, and the χ2 test were used where appropriate. A p value of < .05 was considered statistically significant.Results: Mean maternal age, birth weight and median gravidity, parity and gestational age at delivery were not significantly different between the case and control groups, as well as between the case subgroups (all p > .05). Concentrations of metabolic markers in maternal blood were not significantly different between the two groups (p > .05). Homocysteine and B-type natriuretic peptide levels in cord blood samples were significantly higher, whereas folate levels were significantly lower in the case group compared with the control group (all p < .05). Cord blood B-type natriuretic peptide levels were significantly higher (p < .05) and arterial cord blood pH values were significantly lower (p < .05) in the case subgroup without 6-month infant survival compared with the case subgroup with 6-month infant survival.Conclusion: High cord blood B-type natriuretic peptide and homocysteine levels and low cord blood folate levels at term may be useful for predicting congenital heart disease in the neonate. Neonates with congenital heart disease who have high cord blood B-type natriuretic peptide and low pH values may have adverse outcomes.

Association of High Blood Homocysteine and Risk of Increased Severity of Ischemic Stroke Events.

Stroke is the leading cause of death and disability in the world as well as in Indonesia. Initial stroke severity is an important factor that affects short- and long-term stroke outcomes. This cross-sectional study was conducted in Cipto Mangunkusumo Hospital from July 2017 to January 2018 to investigate the factors that affect stroke severity. A total of 77 acute ischemic stroke patients were divided into three groups, which include low blood homocysteine levels (< 9 μmol/L), moderate blood homocysteine levels (9-15 μmol/L), and high blood homocysteine levels (> 15 μmol/L). The acquired data were analyzed using Kruskal-Wallis test and a significant difference of initial National Institute of Health Stroke Scale (NIHSS) and blood homocysteine levels ( H = 13.328, p = 0.001) were seen, with a mean rank of 25.86 for low blood homocysteine levels, 33.69 for moderate blood homocysteine levels, and 48.94 for high blood homocysteine levels. The patients were then divided into two groups based on the NIHSS (≤5 and > 5) to calculate the risk correlation of blood homocysteine levels and NIHSS by using regression. We found that patients with high blood homocysteine levels had 14.4 times higher risk of having NIHSS > 5 compared with those with low blood homocysteine levels ( p = 0.002, 95% confidence interval [CI] [2.714-76.407]), and 3.9 times higher risk compared with those with moderate blood homocysteine levels ( p = 0.011, 95% CI [1.371-11.246]). We concluded that homocysteine is a risk factor for a higher stroke severity. Future studies to evaluate the usefulness of homocysteine-lowering therapy in stroke patients are recommended.

Evaluation of Serum Homocysteine Levels in Patients with Cutaneous-Oral Lichen Planus and Psoriasis Patients

Background: An elevated plasma homocysteine level is suggested to be a risk factor for reversible atherosclerotic cardiovascular disease. Psoriasis and lichen planus are two chronic inflammatory skin diseases associated with an increased risk of thrombosis and cardiovascular disease. Materials and Methods: We conducted this descriptive analytical study in 2015 on 30 psoriatic patients and 30 patients with cutaneous-oral lichen planus (selected via a simple randomized method) who were referred to the outpatient department of dermatology at Bouali Sina training and therapeutic hospital in Sari, Iran. We evaluated the serum homocysteine, vitamin B12, and folic acid levels in all patients. Data were evaluated using descriptive statistics and an independent t-test. Logistic regression was used for controlling confounding variables. Results: Nine (30%) patients in the psoriasis group and 11 (36.66%) in the cutaneous-oral lichen planus group had abnormally high blood homocysteine level (P = 0.001). Serum vitamin B12 level in the psoriatic group was significantly higher than in the cutaneous-oral lichen planus group (P = 0.034). Both mean and maximum serum folic acid levels in the psoriatic group were higher than in the cutaneous-oral lichen planus group, but the difference was not significant (P = 0.296). As psoriasis and cutaneous-oral lichen planus are chronic inflammatory skin diseases, in these groups, the serum homocysteine levels were higher than in healthy control subjects, but there was no significant differences between the two groups. Conclusion: Further studies are recommended about the course of treatment in patients with psoriasis and lichen planus diseases before therapeutic intervention. [GMJ.2017;6(3):226-232] DOI: 10.22086/gmj.v0i0.749

Hematinic deficiencies and anemia statuses in antigastric parietal cell antibody-positive erosive oral lichen planus patients with desquamative gingivitis.

Erosive oral lichen planus (EOLP) patients with desquamative gingivitis (DG) are sometimes encountered in our oral mucosal disease clinic. This study assessed hematinic deficiencies and anemia statuses in antigastric parietal cell antibody (GPCA)-positive EOLP patients with DG (GPCA+/DG+/EOLP patients). The blood hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations and serum GPCA levels in 92 GPCA+/DG+/EOLP patients and 184 age- and sex-matched healthy controls were measured and compared between the two groups. We found that 27 (29.3%), 16 (17.4%), and 27 (29.3%) of 92 GPCA+/DG+/EOLP patients had hemoglobin (men<13g/dL and women<12g/dL), iron (< 60μg/dL), and vitamin B12 (< 200pg/mL) deficiencies, respectively. Moreover, 37 (40.2%) of 92 GPCA+/DG+/EOLP patients had an abnormally high blood homocysteine level (> 12.1μM). GPCA+/DG+/EOLP patients had a significantly higher frequency of hemoglobin, iron, or vitamin B12 deficiency and an abnormally high blood homocysteine level than healthy control individuals (all p<0.001). Of 27 anemic GPCA+/DG+/EOLP patients, 13 (48.2%) had pernicious anemia, five (18.5%) had iron deficiency anemia, one (3.7%) had thalassemia trait, and the remaining eight (29.6%) had normocytic anemia. Moreover, of the 92 GPCA+/DG+/EOLP patients, 24 had macrocytosis, and only 13 (54.2%) of these 24 patients had pernicious anemia. We conclude that GPCA+/DG+/EOLP patients may have vitamin B12 deficiency, iron deficiency, and an abnormally high blood homocysteine level. In addition to pernicious anemia, GPCA+/DG+/EOLP patients may sometimes have normocytic anemia or iron deficiency anemia.

Evaluation of an Association of Blood Homocysteine Levels With Gastric Cancer Risk From 27 Case-Control Studies.

High blood homocysteine levels may risk gastric cancer. However, observational studies have been plagued by chance, bias, confounding, or reverse causality. In this study, we assessed the relationship between blood homocysteine levels and gastric cancer by using a Mendelian randomization method, which is independent of nongenetic confounding.We took 2 steps to perform Mendelian randomization analysis. First, we evaluated the methylenetetrahydrofolate reductase (MTHFR) C677T association with gastric cancer by a meta-analysis of case-control studies including 7566 patients with gastric cancer and 10 640 control subjects from 27 Case-Control studies. Second, MTHFR C677T polymorphism, which affects the blood homocysteine levels, was used as an instrumental variable to calculate the risk and estimate the association of gastric cancer with this single nucleotide polymorphism (SNP). We obtained an estimate to the association of blood total homocysteine levels with this SNP from a meta-analysis of Genome-Wide Association Studies (GWAS), which comprises a total of 44 147 individuals.In our Mendelian randomization analysis, we demonstrated a significant effect of the blood homocysteine levels on gastric cancer risk, representing an OR of 2.56 (95% CI = 2.41-2.72; P = 5.0×10) for gastric cancer per 1-SD increase in the natural log-transformed blood total homocysteine levels.We proved that there is a causal relationship between blood total homocysteine and risk of gastric cancer, and this study will add insight into the treatment and pathology research of gastric cancer.

Do all the patients with vitamin B12 deficiency have pernicious anemia?

Vitamin B12 deficiency may result in pernicious anemia (PA). This study evaluated whether all the patients with vitamin B12 deficiency had PA. The blood hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine concentrations and mean corpuscular volume (MCV) in 90 vitamin B12-deficient patients were measured and compared with the corresponding data in 180 age- and sex-matched healthy control subjects. PA was defined by World Health Organization (WHO) as having an Hb concentration <13 g/dl for men and <12 g/dl for women, an MCV ≧ 100 fl, a serum vitamin B12 level <200 pg/ml, and serum gastric parietal cell antibody (GPCA) positivity. We found that 35 (38.9%) and 20 (22.2%) patients with vitamin B12 deficiency had deficiencies of Hb (men <13 g/dl, women <12 g/dl) and iron (<60 μg/dl), respectively. Moreover, 65 (72.2%) and 37 (41.1%) patients with vitamin B12 deficiency had abnormally high blood homocysteine level (>12.7 μM) and high MCV (≧100 fl), respectively. In addition, 43 (47.8%) vitamin B12-deficient patients with had GPCA positivity. Patients with vitamin B12 deficiency had a significantly higher frequency of Hb or iron deficiency, of abnormally elevated blood homocysteine level or high MCV, and of GPCA positivity than healthy control subjects (all P-values < 0.001). However, only 17 (18.9%) of 90 vitamin B12-deficient patients were diagnosed as having PA by the WHO definition. Only 18.9% of patients with vitamin B12 deficiency are discovered to have PA by the WHO definition.

Hematinic deficiencies and pernicious anemia in oral mucosal disease patients withmacrocytosis.

Macrocytosis is defined as having the mean corpuscular volume (MCV) ≥ 100 fL. This study assessed hematinic deficiencies and pernicious anemia (PA) in oral mucosal disease patients with macrocytosis. The blood hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine concentrations and MCV in 60 oral mucosal disease patients with macrocytosis were measured and compared with the corresponding data in 120 age- and sex-matched healthy control participants. PA was defined by the World Health Organization (WHO) as having an Hb concentration < 13 g/dL for men and < 12 g/dL for women, an MCV ≥ 100 fL, a serum vitamin B12 level < 200 pg/mL, and serum gastric parietal cell antibody (GPCA) positivity. We found that 30 (50.0%), 7 (11.7%), 24 (40.0%), and three (5.0%) oral mucosal disease patients with macrocytosis had deficiencies of Hb (men < 13 g/dL, women < 12 g/dL), iron (< 60 μg/dL), vitamin B12 (< 200 pg/mL), and folic acid (< 4 mg/mL), respectively. Moreover, 38 (63.3%) and 16 (26.7%) macrocytosis patients had abnormally high blood homocysteine level (> 12.3 μM) and serum GPCA positivity, respectively. Macrocytosis patients had a significantly higher frequency of Hb, iron, or vitamin B12 deficiency, of abnormally elevated blood homocysteine level, and of GPCA positivity than healthy control participants (p < 0.001). However, only 16.7% of 60 macrocytosis patients were diagnosed as having PA by the WHO definition. Only 16.7% of oral mucosal disease patients with macrocytosis are discovered to have PA by the WHO definition.

Blood profile of oral mucosal disease patients with both vitamin B12 and iron deficiencies.

Vitamin B12 and iron deficiencies lead to macrocytosis [mean corpuscular volume (MCV)≥100fL] and microcytosis (MCV<80fL), respectively. This study evaluated anemic status, MCV, serum homocysteine level, and serum gastric parietal cell antibody (GPCA) level in oral mucosal disease patients with both vitamin B12 and iron deficiencies. The blood hemoglobin (Hb), iron, vitamin B12, folic acid and homocysteine concentrations, MCV, and serum GPCA in 149 patients with both vitamin B12 and iron deficiencies were measured and compared with the corresponding data in 149 age- and sex-matched healthy control subjects. We found that 54 (36.2%), 16 (10.7%), 44 (29.5%), and 36 (24.2%) patients with both vitamin B12 and iron deficiencies had Hb deficiency (men <13g/dL, women <12g/dL), folic acid deficiency (≤6mg/mL), abnormally high blood homocysteine level (>12.6μM), and serum GPCA positivity, respectively. Patients with both vitamin B12 and iron deficiencies had a significantly higher frequency of Hb deficiency, abnormally elevated blood homocysteine level, and serum GPCA positivity than healthy control subjects (all p values<0.001). Of 149 patients with both vitamin B12 and iron deficiencies, 10 (6.7%) had high MCV (≥100fL), 108 (72.5%) had normal MCV (between 80fL and 99fL), and 31 (20.8%) had low MCV (<80fL). Approximately 73%, 30%, and 24% of patients with both vitamin B12 and iron deficiencies are found to have normal MCV, abnormally high blood homocysteine level, and serum GPCA positivity, respectively.

Significant association of deficiencies of hemoglobin, iron, folic acid, and vitamin B12 and high homocysteine level with oral lichen planus

A portion of patients with oral lichen planus (OLP) may have nutritional deficiency. This study evaluated whether there was an intimate association of the deficiencies of hemoglobin (Hb), iron, vitamin B12, and folic acid and high blood homocysteine level with OLP. The blood Hb, iron, vitamin B12, folic acid, and homocysteine concentrations in 352 OLP patients were measured and compared with the corresponding levels in 352 age- and sex-matched healthy control participants. We found that 77 (21.9%) OLP patients, 48 (13.6%) OLP patients, 25 (7.1%) OLP patients, and one (0.3%) OLP patient had deficiencies of Hb (men < 13g/dL, women < 12g/dL), iron (< 60μg/dL), vitamin B12 (< 200pg/mL), and folic acid (< 4ng/mL), respectively. Moreover, 52 (14.8%) OLP patients had abnormally high blood homocysteine level. OLP patients had a significantly higher frequency of Hb, iron, or vitamin B12 deficiency and of abnormally elevated blood homocysteine level than healthy control participants (all p<0.001). Upon further dividing OLP patients into those with major erosive OLP (MjEOLP; n=67), minor erosive OLP (n=202), and nonerosive OLP (NEOLP; n=83), we found that MjEOLP patients had a significantly higher mean homocysteine level than NEOLP patients (p=0.035). We conclude that there is a significant association of deficiencies of Hb, iron, folic acid, and vitamin B12 and abnormally high blood homocysteine level with OLP. There may be a close relation of high blood homocysteine level to severity of OLP.

Family History and Functional Outcome in Korean Stroke Patients: A Preliminary Study.

ObjectiveTo investigate the association of family history of stroke with functional outcomes in stroke patients in Korea.MethodsA case-control study was conducted. A total of 170 patients who were admitted to a rehabilitation unit were included. Risk factors for stroke such as age, sex, diabetes mellitus, hypertension, atrial fibrillation, smoking, high blood cholesterol and homocysteine level, obesity, and family history of stroke were taken into account. Stroke subtypes were the following: large vessel infarct, small vessel infarct, embolic infarct, subarachnoid hemorrhage, and intracranial hemorrhage. Stroke severity as assessed with the National Institutes of Health Stroke Scale (NIHSS), functional outcomes using the Korean version of the Modified Barthel index (K-MBI), Functional Independence Measurement (FIM), and cognitive function using the Korean version of Mini-Mental State Examination (K-MMSE) were assessed at admission and discharge.ResultsSubjects with a family history of stroke were more likely to have an ischemic stroke (90.7%) than were those without a family history (70.9%). The K-MBI, FIM, NIHSS, and K-MMSE scores did not show significant differences between patients with or without family history.ConclusionFamily history of stroke was significantly associated with ischemic stroke, but not with functional outcomes. Other prognostic factors of stroke were not distributed differently between patients included in this study with or without a family history of stroke.

Significant association of deficiencies of hemoglobin, iron, vitamin B12, and folic acid and high homocysteine level with recurrent aphthous stomatitis.

A portion of patients with recurrent aphthous stomatitis (RAS) may have nutritional deficiency. This study evaluated whether there was an intimate association of the deficiencies of hemoglobin, iron, vitamin B12, and folic acid and high blood homocysteine level with RAS. The blood hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations in 273 RAS patients were measured and compared with the corresponding levels in 273 age- and sex-matched healthy control subjects. We found that 57 (20.9%), 55 (20.1%), 13 (4.8%), and 7 (2.6%) RAS patients had deficiencies of hemoglobin (Men < 13 g/dl, Women < 12 g/dl), iron (<60 μg/dl), vitamin B12 (<200 pg/ml), and folic acid (<4 ng/ml), respectively. Moreover, 21 (7.7%) RAS patients had abnormally high blood homocysteine level. RAS patients had a significantly higher frequency of hemoglobin, iron, vitamin B12, or folic acid deficiency and of abnormally elevated blood homocysteine level than healthy control subjects (all P-values = 0.000 except for folic acid P = 0.022). If 273 RAS patients were further divided into 32 patients with major-typed RAS (MjRAS) and 241 patients with minor-typed RAS (MiRAS), we found that male MjRAS patients had a significantly lower mean hemoglobin concentration than MiRAS patients (P = 0.021), but MjRAS patients had a significantly higher mean homocysteine level than MiRAS patients (P = 0.000). We conclude that there is a significant association of deficiencies of hemoglobin, iron, vitamin B12, and folic acid and abnormally high blood homocysteine level with RAS.