Risk Of Hyperhomocysteinemia Research Articles

Association between sleep duration and the risk of hyperhomocysteinemia among adults in the United States: National Health and Nutrition Examination Survey, 2005–2006

The study aimed to discuss the association between sleep duration and the risk of hyperhomocysteinemia (Hhcy). This cross-sectional study included 4173 adults (≥ 20 years) from the National Health and Nutrition Examination Survey 2005–2006. According to their sleep duration, participants were divided into five subgroups. Multivariate logistic regression analysis models and restrictive cubic spline regressions were used to explore the association between sleep duration and the risk of Hhcy. Compared with the participants who sleep 7 h, sleep deprivation (≤ 5 h) increased the risk of Hhcy, odds ratio (OR) 1.68 (95% confidence interval (CI) 1.06–2.68); Excessive sleep (≥ 9 h) also increased the risk of Hhcy, OR 1.86 (95% CI 1.09–3.14) after adjusting for a series of confounding factors in the entire population. The risk of Hhcy was distributed in a U-shape with sleep duration. Similar results were demonstrated in obese populations. The association between sleep duration and the risk of Hhcy is U-shaped. Both sleep deprivation and excessive sleep can increase the risk of Hhcy.

Association of Triglyceride-Glucose Index with the Risk of Hyperhomocysteinemia Among Chinese Male Bus Drivers: A Longitudinal Study.

Insulin resistance (IR) and hyperhomocysteinemia (HHcy) are significant risk factors for cardiovascular disease (CVD). As an important marker for IR, Triglyceride-Glucose (TyG) index maybe a significant predictor for HHcy progression, reflecting cardiovascular risk. However, the relationship between TyG index and HHcy has been unknown, especially for the high-risk occupation group of male bus drivers. This longitudinal study was initially conducted to explore the outcome of TyG index in predicting HHcy among male bus drivers. In total, 1018 Chinese male bus drivers with Hcy data and regular follow-up from 2017 to 2021 were screened, and 523 non-HHcy subjects at baseline were included in the longitudinal cohort. A restricted cubic spline (RCS) was performed to investigate the possible non-linear relationship between TyG index and the progression of HHcy. A multivariate logistic regression model was used to explore the association between TyG index and developing HHcy via assessing the value of odds ratio (OR) and 95% confidence interval (CI). After the median follow up time of 2.12 years, approximately 27.7% of male bus drivers (mean age: 48.1 years) was identified as new incidents HHcy. Multivariate logistic regression found that the higher level of TyG was associated with an increased risk of new onset HHcy (OR = 1.47; 95% CI: 1.11-1.94); and the association seemed to be strong among male bus drivers with elevated low-density lipoprotein cholesterol (LDL-C) (P for interaction < 0.05). As a higher risk occupation group for HHcy, male bus drivers should cause much more attentions from policy makers, employers, and health professionals in China. Identifying male bus drivers with HHcy is of significance at an earlier stage in the primary care setting. Being a significant predictive factor for HHcy, TyG index could be used to monitor and prevent Chinese male bus drivers from HHcy, especially for individuals with elevated LDL-C.

Association between body fat composition and hyperhomocysteinemia in the analysis of the baseline data of the Northwest China Natural Population Cohort: Ningxia Project (CNC-NX).

The authors conducted an observational study to explore the association between body fat composition and the risk of hyperhomocysteinemia (HHcy) and their combined effect on the risk of developing cardiovascular disease (CVD). Adults aged 18-74years from the Northwest China Natural Population Cohort: Ningxia Project (CNC-NX) were recruited in this study. Association between body fat composition and HHcy was evaluated by logistic regression model. Restricted cubic spline was used to find nonlinear association. The impact of the interaction between HHcy and body fat composition on CVD was evaluated using the addition interaction model and mediation effect model. In total, 16419 participants were included in this research. Body fat percentage, visceral fat level, and abdominal fat thickness were positively associated with overall HHcy (p for trend<.001). Adjusted odds ratios (ORs) in quarter 4 were 1.181 (95% CI: 1.062, 1.313), 1.202 (95% CI: 1.085, 1.332), and 1.168 (95% CI: 1.055, 1.293) for body fat percentage, visceral fat level, and abdominal fat thickness, respectively, compared with those in quarter 1. Subgroup analysis indicated age, estimated glomerular filtration rate (eGFR), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and CVD were the interaction factors of body fat percentage, visceral fat level, abdominal fat thickness with HHcy (all p for interaction<.05). ORs of CVD were higher in participants with HHcy and high body fat. Body fat composition was positively associated with HHcy, indicating that reducing body, abdominal, and visceral fat content may lower the risk of HHcy and CVD.

Serum uric acid concentration is associated with hyperhomocysteinemia in hypertensive Chinese adults.

This study is to investigate the correlation between serum uric acid levels and hyperhomocysteinemia Chinese adult patients with hypertension. We enrolled 981 hypertensive patients, including unmedicated hypertensives, in our study. There were 453 patients with hyperhomocysteinemia (hyperhomocysteinemia hypertension group) and 528 without it (ordinary hypertension group). We collected histories of coronary heart disease, diabetes, and smoking and tested patients' BMI, blood pressure, fasting serum uric acid, serum total cholesterol, triglycerides, low-density lipoprotein cholesterol, serum creatinine, and homocysteine. Subjects were stratified into four groups according to their serum uric acid quartiles: Q1 group, 249 cases (≤268 μmol/L); Q2 group, 245 cases (269-322 μmol/L); Q3 group, 244 cases (323-378 μmol/L); and Q4 group, 243 cases (≥379 μmol/L). We employ logistic regression analysis to investigate the relationship between serum uric acid levels and the risk of hyperhomocysteinemia in patients with hypertension. We find that there were significant differences in gender distribution, serum uric acid, BMI, serum creatinine, total cholesterol, and diastolic blood pressure between the two groups (P < 0.05). The prevalence of hyperhomocysteinemia in groups Q1 through Q4 was 26.91% (67/249), 45.31% (111/245), 47.01% (117/244), and 65.02% (158/243), respectively, after adjusting for relevant factors, we find that the risk of hyperhomocysteinemia in the Q4 group was significantly higher than that in the Q1 group (odds ratio = 3.00, 95% confidence interval: 1.83-4.93). We find evidence that an elevated serum uric acid level is an independent indicator for hyperhomocysteinemia in patients with hypertension.

Higher Blood Selenium Level is Associated with Lower Risk of Hyperhomocysteinemia in the Elderly

Higher Blood Selenium Level is Associated with Lower Risk of Hyperhomocysteinemia in the Elderly

Association of Obesity with the Risk of Hyperhomocysteinemia among the Chinese Community Residents: A Prospective Cohort Study in Shanghai, China.

A prospective community-based cohort study was conducted to investigate the effects of obesity on hyperhomocysteinemia (HHcy) in community residents from Shanghai, China, with a median follow-up period of 2.98 years. The exposures were high body mass index (BMI) (BMI ≥ 28.0 kg/m2) and high waist circumference (WC) (WC ≥ 85.0 cm for female and WC ≥ 90.0 for male) at baseline investigation, and the outcome was the incident of HHcy after the follow-up. A restricted cubic spline (RCS) was performed to assess the possible nonlinear relationship of BMI and WC with HHcy. A Cox proportional hazard regression model was used to evaluate the association between BMI and WC measured obesity and the risk of HHcy (Hcy level > 15 µmol/L). No significant non-linearity was found between BMI and WC with HHcy. Cox regression model showed that underweight measured by BMI was negatively associated with the risk of HHcy after controlling for confounder variables (adjusted HR = 0.64, 95% CI = 0.42 to 0.99). While abdominal obesity was positively associated with the risk of HHcy for those without CVD-related comorbidities (adjusted HR = 1.26, 95% CI = 1.05 to 1.51). Our results suggested that individuals could maintain a relatively low BMI and normal WC to lower the risk of HHcy.

1400Central but not general obesity is positively associated with risk of hyperhomocysteinemia in middle-aged women

Abstract Background Obesity and homocysteine (Hcy) are two important risk factors for cardiovascular disease (CVD); however, there were conflicting results for the relationship between them. Our study is to explore the associations of general and central obesity with hyperhomocysteinemia (HHcy) in middle-aged women. Methods The current analysis was based on data from 11007 women aged 40-60 years. Height, weight, and waist circumference (WC) were measured and serum homocysteine was determined. Multiple logistic regression models were used to assess the associations of the risk of hyperhomocysteinemia (HHcy, Hcy&amp;gt;15μmol/L) with BMI and WC. Results 13.71% women had HHcy. The prevalences of BMI-based general obesity and WC-based central obesity were 11.17% and 22.88%, respectively. Compared with non-obese women, the mean serum Hcy concentration was significantly higher in WC-based central obese women (P = 0.002), but not in BMI-based general obese women (P &amp;gt; 0.05). In the multiple logistic regression models, central obesity was positively related to the risk of HHcy (OR = 1.30, 95%CI=1.10 to 1.52), while general obesity was inversely related to the risk of HHcy (OR = 0.82, 95%CI=0.72 to 0.93 and OR = 0.71,95% CI = 0.57 to 0.89). Conclusions Central obesity was positively, while general obesity was negatively related to the risk of HHcy. Menopause showed no effect modification on these associations. Key messages Homocysteine; Central obesity; Menopause; Cardiovascular Disease

Association of MTHFR C677T (rs1801133) and A1298C (rs1801131) Polymorphisms with Serum Homocysteine, Folate and Vitamin B12 in Patients with Young Coronary Artery Disease.

C677T (rs1801133) and A1298C (rs1801131) MTHFR gene polymorphisms and/or nutritional deficiency of folate/vitamin B12 leading to hyperhomocysteinemia is an established risk factor for CAD. The objective of this study was to evaluate the clinical usefulness of association between MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms with serum homocysteine, folate and vitamin B12 in addition to conventional cardiovascular risk factors in patients with young CAD. Genomic DNA was isolated from the whole blood. Genotyping of MTHFR C677T (rs1801133) and MTHFR A1298C (rs1801131) polymorphisms in young CAD patients and healthy controls was performed by ARMS-PCR method. Serum homocysteine, vitamin B12 and folate were estimated by CMIA and lipid profile parameters were measured by automated chemistry analyzers. Serum homocysteine levels were significantly higher but serum folate and vitamin B12 levels were not significantly different among young CAD group as compared to control group. Statistically significant hyperhomocysteinemia was observed in carriers of T allele for MTHFR 677C/T (rs1801133) genotype in young CAD group but this association was not significant for MTHFR 1298A/C (rs1801131) polymorphism. The association between hyperhomocysteinemia and CAD in young group was not independent of conventional cardiovascular risk factors. Risk of hyperhomocysteinemia and young CAD could be monitored by MTHFR polymorphism detection followed by serum homocysteine, folate and vitamin B12 measurements. The findings could help to prevent or delay the occurrence of young CAD through appropriate measures.

A novel approach in the management of hyperhomocysteinemia

Hyperhomocysteinemia (Hhcy) is a biochemical alteration with plasma levels of homocysteine higher than 15 µmol/L, associated with atherosclerosis, and with vascular thrombosis by disrupting endothelial cells. Homocysteine is a sulfur-containing amino acid derived from methionine which is an essential amino acid. Excess homocysteine produced in the body is expelled out by liver and kidney from the systemic circulation. Hhcy is caused by the excess deficiencies of the vitamins like pyridoxine (B6), folic acid (B9), or cyanocobalamin (B12). High protein consumers are usually at risk for hyperhomocysteinemia because of low plasma B12 levels. It is approximated that mild Hhcy occurs in 5–7% of the general population and 40% in patients with vascular disease. Patients with heart failure, impaired renal function, and diabetes should be screened since the prevalence of Hhcy in these patients appears to be quite high. In this article, we hypothesise that citicoline is a novel drug for the management of Hhcy. Furthermore, the side effects of citicoline are also minimal and self-limiting. If this strategy is validated, citicoline will be the cost-effective way to be administered for Hhcy. Many evidences are available which suggest that ignoring homocysteine levels in patients with the vascular disease would be unwise. Thus, there is an urgent need for health care providers to develop effective preventions and interventions program (folic acid, Vitamin B6 and Vitamin B12 supplementation as well as lifestyle change) to reduce this disorder.

Association between shift work and hyperhomocysteinemia in male workers.

BackgroundShift work is associated with a higher risk of cardiovascular diseases. Here, we sought to assess the relationship between shift work and plasma homocysteine levels. Determining the correlations between shift work and homocysteine levels may provide a better understanding of the mechanisms underlying cardiovascular diseases.MethodsThis study was performed using data from routine health examinations of steel workers in 2017. In total, 431 male workers (70 daytime workers and 361 shift workers) employed on a rolling departure schedule were recruited. Plasma homocysteine levels > 15 μmol/L were considered elevated. The χ2, analysis of variance, and multiple logistic regression analyses were used to examine the association between shift work and plasma homocysteine levels.ResultsIn comparison to daytime workers, the odds ratio (OR) of hyperhomocysteinemia in individuals with < 10 years of shift work was 1.14 (95% confidence interval [CI]: 0.64–2.03), compared to 2.01 (95% CI: 1.14–3.54) for workers with ≥ 10 years of experience. After adjusting for confounding variables, the adjusted OR for shift workers with < 10 years of experience was 0.95 (95% CI: 0.50–1.80), compared to 2.00 (95% CI: 1.07–3.74) for workers with ≥ 10 years of experience.ConclusionsThe risk of hyperhomocysteinemia was significantly higher in shift workers compared to those working normal daytime hours, particularly among long-term shift workers.

Hyperhomocysteinemia and Folate Deficiency in Preterm Premature Rupture of Membranes: A Hospital Based Case Control Study (India)

Abstract Aim: To understand the role of hyperhomocysteinemia in association with nutritional (folate and vitamin B12) factors involved in one carbon metabolic pathway in the causation of preterm premature rupture of membranes (PPROM). Methods: The case group (women presenting with PPROM) is compared with gestation matched pregnant women without PPROM or any bad obstetric history. Data on demographic, clinical and reproductive profile was obtained from all the women. Fasting blood sample (~5ml) was drawn followed by serum folate, vitamin B12 and plasma homocysteine level estimations. Results: Hyperhomocysteinemia and folate deficiency were found to be posing 8.46 and 2.9 fold increased risk for PPROM cases as compared to the gestation matched controls respectively. The differences were found to be statistically significant for both risk of hyperhomocysteinemia (p<0.0001) and folate deficiency (p=0.002) for preterm premature rupture of membranes. Conclusion: Hyperhomocysteinemia and folate deficiency are associated with PPROM. Keywords Hyperhomocysteinemia; folate deficiency; vitamin B12; preterm complications; rupture of membranes

Impact of CPS1 Gene rs7422339 Polymorphism in Argentine Patients With Hyperhomocysteinemia

Abstract Carbamoyl phosphate synthetase 1 (CPS1) is a key gene in the first step of urea cycle and has been correlated with nitric oxide level and vascular smooth muscle activity. A functional single-nucleotide polymorphism C/A at position 4217 in CPS1 (National Center for Biotechnology Information SNP database no. rs7422339, T1405N) was reported to be associated with high homocysteine (Hcy) plasma values. Although genetic variants of methylenetetrahydrofolate reductase (MTHFR) gene are known to influence Hcy concentration, other genetic determinants of Hcy remain largely unknown. The association between the CPS1 rs7422339 and the risk of hyperhomocysteinemia in Latin American populations is unknown. Here, we study this association in 100 patients having hyperhomocysteinemia without MTHFR c.677C>T polymorphism and 100 controls. CPS1 rs7422339 was studied using polymerase chain reaction and enzymatic restriction. Comparisons of the CPS1 rs7422339 genotype distributions revealed a significant difference between groups (P = 2.3 × 10−3). Patients carrying polymorphic allele showed almost 3 times higher risk (odds ratio [OR] = 2.47) of hyperhomocysteinemia than wild-type allele, suggesting that rs7422339 SNP is associated with high Hcy levels in the Argentine population.

Hyperhomocysteinemia as a potential contributor of colorectal cancer development in inflammatory bowel diseases: a review.

Homocysteine is an amino acid generated metabolically by the S-adenosylmethionine-dependent transmethylation pathway. In addition to being a well-known independent risk factor for coronary heart disease, is also a risk factor for cancer. Patients suffering from inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease are at increased risk of developing colorectal cancer in comparison to healthy individuals. Furthermore, the risk of hyperhomocysteinaemia is significantly higher in IBD patients when compared with controls. In the present article, we review the mechanisms in which hyperhomocysteinemia may contribute to increased risk of colorectal cancer in IBD patients.

Plasma Homocysteine Concentrations in Dogs

Many human epidemiologic studies have reported associations between plasma homocysteine (Hcy) concentrations and cardiovascular disease, Alzheimer’s disease, and osteoporosis. However, few studies have examined the relationship between Hcy and disease in dogs. In this study, we investigated the relationship between canine plasma Hcy concentrations and sex, age, breed, size; spay/neuter status, and disease. Plasma Hcy concentrations were related to sex and age, but the correlations were very weak. ShibaInu dogs and Labrador Retrievers had a higher risk of hyperhomocysteinemia than other breeds. We compared the plasma Hcy concentrations of healthy control dogs with those of dogs with heart, inflammatory, bone and joint, nervous system, neoplastic, skin, and kidney diseases. The mean plasma Hcy concentrations of dogs with cardiovascular, neoplasia, skin, and kidney diseases were significantly different from those of controls. However, multivariate logistic regression (parameters: Hcy concentration, age, sex, and spay/neuter status) revealed a significant relationship between only skin disease and plasma Hcy concentration. The odds ratio (per 1 μmol/l increase of Hcy) was 1.077 (95% confidence interval 1.00–1.158, p<0.05). Plasma Hcy concentrations significantly differ among dog breeds, and there is a relationship between high plasma Hcy concentration and skin disease.

Meta-analysis: hyperhomocysteinaemia in inflammatory bowel diseases

The magnitude of association between homocysteine metabolism and inflammatory bowel diseases (IBD) remains unknown, whereas the association between hyperhomocysteinaemia and thrombosis remains controversial in IBD. To conduct a systematic review and meta-analysis to examine these issues. The literature search was conducted using MEDLINE database and international conference abstracts from January 1966 to April 2011 and included all studies that evaluated plasma homocysteine level in IBD. Twenty-eight studies evaluated the plasma homocysteine level and/or hyperhomocysteinaemia risk in IBD patients. Five studies assessed the association of hyperhomocysteinaemia with thrombosis. The mean plasma homocysteine level was significantly higher in IBD patients when compared with controls (weighted mean difference (WMD)=3.75 μmol/L; 95% CI, 2.23-5.26 μmol/L; P<0.0001; reference ranges for plasma homocysteine level: 5-12 μmol/L). The mean plasma homocysteine level did not differ between ulcerative colitis (UC) and Crohn's disease (CD) (WMD=0.41 μmol/L; 95% CI, -2.45 to 3.06 μmol/L; P=0.76). The risk of hyperhomocysteinaemia was significantly higher in IBD patients when compared with controls [odds ratio (OR)=4.65; 95% CI, 3.04-7.09; P<0.0001]. The risk of hyperhomocysteinaemia was not higher among IBD patients who experienced thromboembolic complications (OR=1.97; 95% CI, 0.83-4.67; P=0.12). Plasma folate level was inversely correlated with IBD risk associated with MTHFR C677T polymorphism (P=0.006). The risk of hyperhomocysteinaemia is significantly higher in IBD patients when compared with controls. The risk assessment of hyperhomocysteinaemia-related thrombosis in IBD requires further investigation. Deficient folate status is associated with a higher impact of MTHFR C677T polymorphism on IBD risk.

Reference interval and determinants of the serum homocysteine level in a Korean population

In this study, we estimated the reference intervals of the serum homocysteine (Hcy) level using two automated immunoassays, and we demonstrated the effects of various factors on the Hcy level in a Korean population. We calculated the gender- and assay-specific reference intervals using the data from 809 healthy Koreans, and we assessed the effects of physiologic and lifestyle factors on the Hcy level. The upper limit was higher in males (19.21 and 19.76 μmol/l) than that in females (14.99 μmol/l and 15.16 μmol/l, AxSym and ADVIA centaur, respectively); the upper limits were comparable between the two assays. Smokers, vitamin nonusers, and persons without regular exercise showed a lower folate level and a higher Hcy level. The risk of hyperhomocysteinemia was significantly associated with the male gender (adjusted OR: 5.705, P-value: 0.008) and with the low folate level group (adjusted OR: 10.412, P-value: 0.002) on the multivariate analysis. The Hcy level was significantly different according to various factors, especially in the gender and folate level. The reference interval should be determined for each ethnic population and for each assay. The appropriate cutoff for assessing the risk for cardiovascular disease or stroke should also be validated in each population.

Major Determinants of Serum Homocysteine Concentrations in a Korean Population

The objective of this study was to identify the factors that determine serum homocysteine concentrations in Korean population. In a community-based study, 871 participants completed detailed questionnaires and physical examination. We found that increased age, male sex, family history of stroke, deficiencies of serum folate and vitamin B12, and elevated serum creatinine significantly increased the risk of hyperhomocysteinemia. However, hormonal and behavioral factors (smoking, alcohol drinking, coffee consumption, and sedentary time) were not associated with the risk of hyperhomocysteinemia. The risk of hyperhomocysteinemia was steeply increased in subjects with two or more risk factors among four selected risk factors (deficiencies of serum folate and vitamin B12, elevated creatinine, and family history of stroke) compared to subjects who did not have any risk factors, especially subjects over the age of 65 yr (odds ratio [OR], 33.5; 95% confidence interval [CI], 3.71-302.0 in men; OR, 39.2; 95% CI, 7.95-193.2 in women). In conclusion, increased age, male sex, family history of stroke, deficiencies of serum folate and vitamin B12, and elevated serum creatinine are important determinants of serum homocysteine concentrations with interaction effects between these factors.

High prevalence of hyperhomocysteinemia in critically ill patients: Vascular damage and adequate vitamin intake

Summary Aims To determine the prevalence of hyperhomocysteinaemia in critically ill patients and its relationship with endothelial damage and vitamin intake. Methods Total antioxidant capacity, lipid peroxides, and carbonyl group in plasma were measured by spectrophotometry. Homocysteine, D-dimer, B12 vitamin and folic acid levels were determined by immunoassay. Daily diet records were compared with vitamin recommendations in 40 consecutive critically ill patients. Results Homocysteinaemia on day 7 was higher in patients with 12 and folic acid than in patients with higher intakes (16.3 ± 3.1 μm/L vs. 9.3 ± 54 μm/L, p r 2 = 0.65, p r 2 = 0.58, p r 2 = −0.57, p r 2 = 0.47, p Conclusions The present findings appear to support the maintenance of an adequate vitamin intake in critically ill patients to reduce their risk of hyperhomocysteinemia, and therefore microthromboses. However, controlled clinical trials are required to establish any causal relationships.

Screening for C677T and A1298C MTHFR Polymorphisms in Patients With Epilepsy and Risk of Hyperhomocysteinemia

Hyperhomocysteinemia can result from decreased methylenetetrahydrofolate reductase (MTHFR) enzyme activity, owing to genetic polymorphisms andor inadequate folate intake. This study was aimed at investigating the prevalence of C677T and A1298C MTHFR polymorphisms, and their impact on hyperhomocysteinemia in 95 epileptic patients and 98 controls. Double gradient-denaturing gradient gel electrophoresis screening revealed that the frequency of T677 polymorphic allele was similar between cases and controls (46.3% vs 42.3%), whereas that of C1298 allele was significantly higher in patients (30.5% vs 19.4%, p < 0.05). Significant differences between the two groups were also found for the frequencies of genotypes AA1298 (46.3% in cases vs 67.3% in controls, p < 0.01) and AC1298 (46.3% in cases vs 26.6% in controls, p < 0.01). Other genotype frequencies did not show any statistically significant differences. Haplotype frequencies significantly differed between the two groups. The CT677/AC1298 diplotype was significantly more frequent in epileptic patients than in controls (32.6% vs 18.4%, p < 0.05). Patients treated with enzyme-inducing antiepileptic drugs, having this diplotype and concomitant low folate concentration (i.e., < 3.4 nmol/L), exhibited plasma homocysteine levels significantly higher than normal values (27.1 +/- 2.44 micromol/L, p < 0.001). This increase, however, was lower than that observed in folate-deficient patients with diplotype TT677/AA1298 (41.3 +/- 3.41 micromol/L, p < 0.001). Indeed, these two diplotypes could be regarded as risk factors for hyperhomocysteinemia. Conversely, we found that the CC677/AA1298 diplotype was significantly more frequent in controls (p < 0.01), suggesting a protective role. Our study suggests that both C677T and A1298C MTHFR polymorphisms should be examined when assessing genetic risk factors of hyperhomocysteinemia in epilepsy.

Potential Association of Thyrotoxicosis with Vitamin B and Folate Deficiencies, Resulting in Risk for Hyperhomocysteinemia and Subsequent Thromboembolic Events

To describe a patient with severe thyrotoxicosis attributable to Graves' disease who had a thrombotic cerebrovascular accident and hyperhomocysteinuria, which resolved on correction of the thyrotoxicosis, and to present findings in a pilot study undertaken to investigate the relationship among thyrotoxicosis, homocysteine, folate, and vitamin B(12). We present a case report of the index case, with clinical and laboratory details. For the investigative analysis, 21 patients who were 18 to 50 years old and had newly diagnosed, untreated Graves' disease and 10 age-and sex-matched euthyroid control subjects were studied. Of the patients with Graves' disease, 11 underwent studies both at diagnosis and after treatment. Fasting blood tests were performed for thyrotropin, free thyroxine, homocys-teine, vitamin B(12), folate, and methylmalonic acid, a marker of vitamin B(12) deficiency. Vitamin B(12), folate, homocysteine, and methylmalonic acid levels were not significantly different between the thyrotoxic and control or posttreatment groups. In patients with thyrotoxicosis, however, free thyroxine was positively correlated with both homocysteine (r = 0.67; P = 0.03) and methylmalonic acid (r = 0.89; P = 0.003). The positive correlation between free thyroxine levels and both homocysteine and methylmalonic acid suggests that thyrotoxicosis may be associated with functional vitamin B(12) deficiency. Such a deficiency may result in clinically important hyperhomocysteine-mia.