Elevated homocysteine levels in patients with Raynaud's syndrome.

OBJECTIVE: Patients with Raynaud's phenomenon (RP) have vasomotor dysregulation, the etiology of which has not yet been elucidated. We investigated plasma levels of homocysteine and folate in patients with primary or secondary RP in comparison with healthy subjects. METHODS: Plasma from patients with RP, either primary (n = 10) or secondary to scleroderma (n = 10), and from healthy subjects (n = 20) was obtained for homocysteine determination using high performance liquid chromatography. RESULTS: Patients with primary and secondary RP had significantly higher homocysteine concentrations (mean 15.5 +/- 4.1 and 11.6 +/- 6.2 micromol/l, respectively; p < 0.05) compared to healthy individuals (mean 5.9 +/- 2.0 micromol/l). Patients with primary RP had significantly lower plasma levels of folate in comparison with patients with secondary RP or healthy individuals. CONCLUSION: This is the first study to show higher plasma levels of homocysteine in patients with RP. Given the obscure etiology of this disorder, these findings may provide new clues in the understanding of vasomotor dysfunction in RP.     

Effect of B vitamin supplementation on plasma homocysteine levels in celiac disease

AIM： To investigate the effect of vitamin supplements on homocysteine levels in patients with celiac disease. METHODS： Vitamin B6, folate, vitamin B12, and fasting plasma homocysteine levels were measured in 51 consecutive adults with celiac disease [median （range） age 56 （18-63） years; 40% men, 26 （51%） had villous atrophy, and 25 （49%） used B-vitamin supplements] and 50 healthy control individuals matched for age and sex. Finally, the C677T polymorphism of 5,10-methylene tetrahydrofolate reductase （MTHFR） was evaluated in 46 patients with celiac disease and all control individuals. RESULTS： Patients with celiac disease and using vitamin supplements had higher serum vitamin B6 （P = 0.003）,folate （P 〈 0.001）, and vitamin B12 （P = 0.012） levels than patients who did not or healthy controls （P = 0.035, P 〈 0.001, P = 0.007, for vitamin B6, folate, and vitamin B12, respectively）. Lower plasma homocysteine levels were found in patients using vitamin supplements than in patients who did not （P = 0.001） or healthy controls （P = 0.003）. However, vitamin B6 and folate, not vitamin B12, were significantly and independently associated with homocysteine levels. Twenty-four （48%） of 50 controls and 23 （50%） of 46 patients with celiac disease carried the MTHFR thermolabile variant T-allele （P = 0.89）. CONCLUSION： Homocysteine levels are dependent on Marsh classification and the regular use of B-vitamin supplements is effective in reduction of homocysteine levels in patients with celiac disease and should be considered in disease management.     

Homocysteine concentration in primary and systemic sclerosis associated Raynaud's phenomenon

OBJECTIVE: To investigate whether patients with systemic sclerosis (SSc) have raised homocysteine (Hcy) plasma levels, thought to be an independent risk factor for vascular disease, and to study the relationship between Hcy and endothelial damage, and between Hcy and methylene-tetrahydrofolate reductase (MTHFR) genotypes, and patients' vitamin nutritional status, which are among the more frequent causes of hyperhomocysteinemia. METHODS: We measured Hcy, von Willebrand factor (vWF), folic acid, and vitamin B12 plasma levels and analyzed the frequencies of MTHFR mutations in 30 patients with SSc and 12 patients with primary Raynaud's phenomenon (RP); 29 healthy subjects served as controls. RESULTS: Patients with SSc had higher Hcy and vWF concentrations than those with RP (p < 0.01 and p < 0.02, respectively) or controls (p < 0.02 and p < 0.0001, respectively). Folic acid and vitamin B12 were lower in SSc than in RP (p < 0.01 and p < 0.02, respectively) or controls (p < 0.05). MTHFR genotype did not influence Hcy, folate, or vitamin B12 concentrations, but patients homozygous for the mutant gene had higher vWF levels. CONCLUSION: Patients with SSc, but not those with RP, had significantly higher Hcy and vWF plasma levels. Nutritional rather than inherited factors seem to have a pathogenic role in SSc hyperhomocysteinemia.     

Relation of Helicobacter pylori infection to plasma vitamin B12, folic acid,and homocysteine levels in patients who underwent diagnostic coronary arteriography

OBJECTIVE: The aim of this study was to test the hypothesis that chronic atrophic gastritis induced by Helicobacter pylori (H. pylori) causes malabsorption of vitamin B12 and folate in food, leading ultimately to an increase in circulating homocysteine levels. METHODS: We performed endoscopy with stomach biopsy and measured fasting plasma homocysteine, vitamin B12, and folate levels in 93 patients who underwent diagnostic coronary arteriography. The patients were divided into two groups according to the presence (n = 57) or absence (n = 36) of H. pylori infection. Positive H. pylori infection was defined as positive H. pylori histology of biopsy specimens from the stomach. The extent of atrophic gastritis was endoscopically graded from 0 to 6. RESULTS: There were no differences in age, sex, or traditional coronary risk factors between the two groups. Atrophy scores of the stomach were greater in patients with H. pylori infection than in patients without (3.9 +/- 1.4 vs 2.2 +/- 1.8, p < 0.0001). Patients with H. pylori infection had lower levels of vitamin B12 (630 +/- 222 vs 747 +/- 259 pg/ml, p = 0.02) and folate (6.2 +/- 2.1 vs 7.4 +/- 2.8, p = 0.046), as well as higher levels of homocysteine (11 +/- 4.9 vs 8.3 +/- 2.1 nmol/ml, p = 0.01), than did patients without H. pylori infection. Plasma homocysteine levels correlated inversely with plasma vitamin B12 and folate levels and positively with atrophic scores. CONCLUSIONS: This study suggests that H. pylori-induced chronic atrophic gastritis decreases plasma vitamin B12 and folic acid levels, thereby increasing homocysteine levels. However, this effect does not seem to be strong.     

血浆同型半胱氨酸及其代谢酶基因多态性与溃疡性结肠炎的相关性研究

目的 探讨血浆同型半胱氨酸(Hcy)、叶酸和维生素B12水平及Hcy代谢酶基因多态性与溃疡性结肠炎(UC)的关系.方法 收集310例UC患者和936名正常对照者,采用聚合酶链反应-限制性片断长度多态性(PCR-RELP)法检测亚甲基四氢叶酸还原酶(MTHFR)C677T、A1298C、甲硫氨酸合成酶(MTR) A2756G和甲硫氨酸合成还原酶(MTRR) A66G基因多态性;并从中随机选取88例UC患者和100名正常对照者,采用循环酶法检测血浆Hcy水平,微粒子免疫化学发光法检测叶酸和维生素B12浓度.结果 UC患者MTHFR A1298C、MTR A2756G和MTRRA66G突变的等位基因及基因型频率均明显增高(P值均<0.01).UC患者Hcy平均水平为(21.73±6.59)mmol/L,较正常对照组显著增高[(12.47±5.01)mmol/L,P<0.01],而叶酸和维生素B12平均水平分别为(11.25±6.19)nmol/L和(322.81±128.47)pmol/L,明显较正常对照组降低[(15.28±7.72)nmol/L和(422.59±129.36)pmol/L,P值均<0.01].Logistic回归分析提示血浆Hcy、叶酸和维生素B12浓度是UC的独立危险因素(P值均<0.01).结论 Hcy代谢酶基因多态性及血浆Hcy、叶酸和维生素B12水平异常与UC明显相关,为临床采用叶酸、维生素B12补充疗法治疗UC提供了理论依据.     

Influence of a glutamate carboxypeptidase II (GCPII) polymorphism (1561C-->T) on plasma homocysteine,folate and vitamin B(12) levels and its relationship to cardiovascular disease risk

Elevated levels of total homocysteine and low folate in blood are independent and graded risk factors for arterial occlusive disease. An impairment of folate distribution can be an important cause of hyperhomocysteinemia. Glutamate carboxypeptidase II (GCPII) regulates the absorption of dietary folates. In the present study, we examined the relationship of a 1561C-->T variant in the GCPII gene with fasting, post-methionine load plasma homocysteine, folate and vitamin B(12) levels and the risk of cardiovascular disease (CVD) in 190 vascular disease patients and in 601 apparently healthy controls. Fasting as well as post-load homocysteine concentrations associated with the 1561TT genotype tended to be lower, whereas the homocysteine concentrations of the 1561CT individuals were not different from their 1561CC peers. The 1561C-->T polymorphism significantly increased both red blood cell folate and plasma folate concentrations (ANOVA P=0.013; test for linear trend P=0.03, respectively), but had no effect on vitamin B(12) levels (ANOVA P=0.35). Since not only homocysteine itself is considered to be positively associated with the risk of CVD, but also a decreased folate status, the results of this study indicate that the 1561C-->T polymorphism may affect the predisposition to CVD.     

Plasma folate, vitamin B(12), and total homocysteine and homozygosity for the C677T mutation of the 5,10-methylene tetrahydrofolate reductase gene in patients with Alzheimer's dementia. A case-control study.

BACKGROUND: Elevated total plasma homocysteine (tHcy) levels are considered a risk factor for cerebrovascular disease and may also play an important role in the pathogenesis of Alzheimer's disease (AD). High values of plasma tHcy and low levels of vitamin B(12) and folate are frequently present in AD patients. Moreover, the homozygous mutation (C677T) of the methylene tetrahydrofolate reductase (MTHFR) gene, related to a thermolabile type of the encoded enzyme, causes hyperhomocysteinemia by reducing the 5-methyltetrahydrofolate availability. OBJECTIVE: The aim of the study was to investigate plasma levels of folate, vitamin B(12) and tHcy in patients with AD. These values were also related to the severity and the duration of the disease and to the possible role of the MTHFR genotype (C677T). METHOD: Plasma tHcy levels, homozygosity for the C677T mutation of the MTHFR gene, and folate and vitamin B(12) plasma levels were evaluated in 74 patients with AD (45 men, 29 women, mean age 68 years) and in 74 healthy matched controls (42 men, 32 women, mean age 68 years). RESULTS: AD patients had higher mean (+/- SD) plasma levels of tHcy (20.9 +/- 15 micromol/l compared to 11.8 +/- 5 micromol/l, p < 0.001) and lower mean plasma folate (5.7 +/- 2.1 ng/ml compared to 8.5 +/- 3.2 ng/ml, p < 0.001) and vitamin B(12) (491 +/- 144 pmol/l compared to 780 +/- 211 pmol/l, p < 0.001) concentrations. Homozygosity for the C677T mutation of the MTHFR gene had a similar prevalence among controls (18%) and AD patients (20%). Homozygous AD patients (n = 15) had higher plasma tHcy values than nonhomozygotes, in spite of similar mean plasma folate and vitamin B(12) levels. This difference in plasma tHcy levels was not observed in controls. Patients with levels of plasma tHcy above and of plasma folate below the normal limits were more frequent in the homozygous AD group. The duration of the disease correlated with plasma levels of tHcy (r = +0.832, p < 0.001), plasma folate (r = -0.580, p < 0.05), and vitamin B(12) (r = -0.460, p < 0.05). However, when all the data were corrected for age, serum creatinine levels, and duration of the disease, mean plasma tHcy, folate, and vitamin B(12) levels were not statistically different between controls and AD patients. CONCLUSIONS: Our data suggest that rather than a risk factor for AD, hyperhomocysteinemia is related to its progression and increasing severity. This might be particularly relevant in homozygotes for the C677T mutation of the MTHFR gene and supports the possible need for continuous supplements in this setting.     

Age, sex and vitamin status affect plasma level of homocysteine, but hyperhomocysteinaemia is possibly not an important risk factor for venous thrombophilia in Taiwanese Chinese

The biological effects of age, sex and vitamin status on plasma total homocysteine (tHcy), and association of hyperhomocysteinaemia with venous thromboembolism in Taiwanese Chinese individuals, were investigated. Eighty patients (16-85 years) with venous thrombophilia and 123 healthy subjects (15-85 years) without history of vascular thrombosis were studied for plasma levels of tHcy, folate and vitamin B12. A multivariate analysis in healthy subjects revealed that plasma tHcy levels tended to increase with age (P < 0.001) and with decreasing plasma levels of folate (P=0.001) or vitamin B12 (P < 0.029); men tended to have higher plasma tHcy levels than women (P=0.006). Thrombotic risk assessment in a case-control study demonstrated that neither plasma level of tHcy [odds ratio (OR), 1.07; 95% confidence interval (CI), 0.96-1.18; P=0.210] nor hyperhomocysteinaemia (OR, 1.65; 95% CI, 0.50-5.49; P=0.415) was significantly associated with venous thrombophilia. The relationship between hyperhomocysteinaemia and recurrence of episode remained insignificant (P=0.560). We conclude that age, sex and vitamin status affect plasma tHcy but hyperhomocysteinaemia is possibly not an important risk factor for venous thrombophilia in Taiwanese Chinese.     

Elevated homocysteine levels with weight loss after Lap-Band surgery: higher folate and vitamin B12 levels required to maintain homocysteine level.

OBJECTIVE: To investigate homocysteine levels and their relationship with serum folate and vitamin B12 concentrations with weight loss after the Lap-Band form of gastric restrictive surgery, with the view to minimizing risk. METHODS: We measured levels of fasting plasma homocysteine (tHcy), folate (serum and RBC) and vitamin B12 in two groups. The study group was 293 consecutive patients at 12 (n=192) or 24 (n=101) months review after surgery. The controls were 244 consecutive patients presenting for this surgery. RESULTS: The group losing weight had higher geometric mean tHcy levels: 10.4 (95% CI, 9.8-10.8) micromol/l compared with 9.2 (95% CI, 8.9-9.7) in controls (P<0.001). This occurred with higher folate levels and unchanged vitamin B12 levels. Levels of folate and B12 together explained 35% (r (2)) of the homocysteine variance in the weight loss group compared with only 9% (r (2)) in controls (P<0.001). Those taking regular multivitamin supplements had lower tHcy levels: 9.6 (9.1-10.0) micromol/l vs 12.3 (11.4-13.3) in those not taking supplements (P<0.001). A low normal plateau of tHcy levels occurred at levels of folate >15 ng/l and B12)600 ng/ml. A curvilinear relationship exists between these cofactors and tHcy levels, with the dose-response relationship shifted to the right in the weight loss group. CONCLUSION: This study shows elevated tHcy levels with weight loss, without lower serum folate or vitamin B(12) levels. There is an altered dose-response relationship with higher serum B(12) and folate levels required to maintain recommended tHcy levels. Patients losing weight have significant health benefits; however, they may be at greater risk of vascular events or fetal abnormality in association with raised tHcy levels. Multivitamin supplementation is effective in lowering tHcy levels.     

Hyperhomocysteinemia and inflammatory bowel disease: prevalence and predictors in a cross-sectional study

OBJECTIVE: Homocysteine is a sulfur-containing amino acid formed during the demethylation of methionine. Vitamin B12 and folate deficiency and therapy with antifolate drugs may predispose patients with inflammatory bowel disease (IBD) to hyperhomocysteinemia. The known associations between hyperhomocysteinemia and smoking, osteoporosis, and thrombosis make it an interesting candidate as a pathogenetic link in IBD. The aim of this study was to identify the prevalence and risk factors of hyperhomocysteinemia in patients with IBD. METHODS: Sixty-five consecutive IBD patients were recruited from a tertiary outpatient gastroenterology practice. Fasting plasma homocysteine levels were measured, along with vitamin B12 and folate. Data regarding medication use, multivitamin use, disease location and severity, and extraintestinal manifestations of IBD were gathered. Homocysteine levels in 138 healthy control subjects were compared with the IBD cohort, and adjustments for age and sex were made using logistic regression. Multivariate analysis was performed to seek predictors of homocysteine levels. RESULTS: The mean age in the IBD cohort was 42+/-13.4 yr (+/-SD), and 43% were male. The mean disease duration was 13.8+/-9.4 yr, and 32% had used steroids within the last 3 months. Immunomodulator therapy had been used in 32%, and 75% had had an intestinal resection. Osteoporosis was present in 33% of patients. Five patients had experienced venous thrombosis or stroke, but only one of these had hyperhomocysteinemia. Of the 10 IBD patients (15.4%) with hyperhomocysteinemia, only two had vitamin B12 deficiency. The homocysteine levels in the IBD cohort cases and controls were 8.7 and 6.6 micromol/L, respectively (p < 0.05). IBD significantly increased the risk of hyperhomocysteinemia (adjusted odds ratio = 5.9 [95% CI: 1.5-24]). Advanced age, male sex, vitamin B12 deficiency or lower vitamin B12 serum levels, and multivitamin therapy were independently associated with higher homocysteine levels in the multivariate analysis (R2 = 0.55; p = 0.001). CONCLUSIONS: Hyperhomocysteinemia is significantly more common in patients with IBD compared with healthy controls, and is associated with lower (but not necessarily deficient) vitamin B12 levels.     

Homocysteine levels in vegetarians versus omnivores

Vitamin B(12), folate, and vitamin B(6) are the main determinants of homocysteinemia. The vegan diet provides no vitamin B(12), but also less strict forms of alternative nutrition may suffer from a deficit of this vitamin. The plasma homocysteine level was measured in alternative nutrition groups of adults (lacto- and lactoovovegetarians, n = 62; vegans, n = 32) and compared with the levels in a group consuming traditional diet (n = 59), omnivores). In the group of vegetarians the average homocysteine level is 13.18 vs. 10.19 micromol/l in omnivores; the frequency of hyperhomocysteinemia is 29 vs. 5% in omnivores. In the group of vegans the average homocysteine value is 15.79 micromol/l (53% of the individual values exceeded 15 micromol/l). Omnivores consume the recommended amount of methionine; however, in individuals consuming an alternative diet, the intake of methionine is deficient (assessed by food frequency questionnaire; lower content of methionine in plant proteins). Under conditions of lower methionine availability the remethylation pathway prevails; therefore, vitamin B(12) and folate were evaluated in relation to the homocysteine level. The serum vitamin B(12) levels are significantly lower in the alternative nutrition groups (214.8 pmol/l in vegetarians, 140.1 pmol/l in vegans vs. 344.7 pmol/l in omnivores); a deficit (<179.0 pmol/l) was found in 26% of the vegetarians and in 78% of the vegans vs. 0% in omnivores. The serum folate levels were within the range of reference values in all groups; however, they were significantly lower in omnivores. The results show that the mild hyperhomocysteinemia in alternative nutrition is a consequence of vitamin B(12) deficiency.     

Association of low red blood cell folate concentrations with coronary artery disease in Iranians: a matched case-control study

BACKGROUND: It is not fully established whether the increasing risk of coronary artery disease (CAD) is associated with high plasma homocysteine levels or components of the homocysteine remethylation pathway, e.g. vitamin B(12) or 5-methyltetrahydrofolate (5-MTHF) in plasma and red blood cells (RBC). In this study, we tested the hypothesis that 5-MTHF in RBC, which represents the long-term folate status of individuals, may be a more reliable marker of homocysteine remethylation pathway disturbances, and its deficiency may be associated with CAD in Iranians. METHODS: Plasma total homocysteine (tHcy), vitamin B(12), and plasma and RBC 5-MTHF were measured in 200 angiographically documented patients and 200 controls matched for sex and age. RESULTS: In the plasma, tHcy levels were significantly higher in cases compared to controls (geometric mean 12.9 +/- 6.5 vs. 10.6 +/- 5.6 micromol/l, p = 0.04). However, RBC 5-MTHF (527.2 +/- 185.9 vs. 461.3 +/- 117.9 nmol/l, p = 0.007) and vitamin B(12) (254.2 +/- 132.8 vs. 182.2 +/- 110.4 pmol/l, p = 0.04) were significantly higher in controls than patients. RBC 5-MTHF was a strong and independent predictor of plasma tHcy (beta = -0.01, p = 0.003, r(2) = 0.19). Subjects in the lowest quartile of red-cell 5-MTHF had a 2.5-fold increased prevalence of CAD compared to subjects in the highest quartile. The association of CAD in the first quartile with red-cell 5-MTHF remained significant when adjusted for plasma tHcy, vitamin B(12), hypertension and hypercholesterolemia (odds ratio, OR 2.3, confidence interval: 1.1-3.9, p = 0.01). However, the association between CAD in the highest quartile and plasma tHcy decreased and became insignificant when adjusted for red-cell 5-MTHF, vitamin B(12), hypertension and hypercholesterolemia (OR 1.27, confidence interval: 0.96-1.69, p = 0.11). CONCLUSION: In this study, the association between CAD and low RBC 5-MTHF was stronger than with plasma 5-MTHF and plasma tHcy levels, indicating that RBC 5-MTHF may be a more stable parameter to study disturbances in the homocysteine remethylation pathway in Iranians.     

Homocysteine, folate and vitamin b12 in patients with coronary heart disease

BACKGROUND/AIMS: Homocysteine and possibly also folate and vitamin B(12) are involved in the pathogenesis of cardiovascular disease. We investigated the prevalence of hyperhomocysteinemia in patients with coronary heart disease (CHD), as well as folate and vitamin B(12), the main nutritional factors determining the level of homocysteine. METHODS: Patients with angiographically documented CHD were prospectively investigated (n = 315, 70% male, mean age 61 [range 36-81] years). Fasting total serum homocysteine was determined by high-performance liquid chromatography and fluorescence detection. Folic acid and vitamin B12 were measured with AxSYMR Systems. RESULTS: Median homocysteine concentrations for homocysteine, folate and vitamin B12 were 12.8 micromol/l, 6.8 ng/ml and 345 pg/ml, respectively. Homocysteine levels >10 micromol/l were found in 82% of men and 73% of women. In 19% of the patients serum folate was <3 ng/ml and 22% of the patients had serum vitamin B12 values <250 pg/ml. In a multivariate linear regression model, folate and vitamin B(12) showed significant negative correlations to homocysteine, explaining 5 and 3% of its variability. Age and creatinine were the most important determinants for serum homocysteine, contributing 12 and 7%, respectively. DISCUSSION: The main determinants of total homocysteine in patients with CHD are higher age and increased creatinine. The association of lower levels of folate and vitamin B12 with higher levels of homocysteine may indicate poor dietary habits in these patients.     

Reduced folate, increased vitamin b(12) and homocysteine concentrations in women delivering preterm

Background and Aim: Maternal nutrition is an important determinant of the duration of pregnancy and fetal growth, and thereby influences pregnancy outcome. Folic acid and vitamin B(12) are involved in one-carbon metabolism and are reported to underlie intrauterine programming of adult diseases. Methods: In the present study, the levels of folate, vitamin B(12) and homocysteine were measured in mothers delivering preterm (PT; gestation <37 weeks; n = 67), those delivering preterm due to preeclampsia (PT-PE; n = 49) and women delivering at term (control group; n = 76). Results: Increased vitamin B(12) and homocysteine levels (p < 0.05 for both) were seen in the PT-PE and PT groups as compared to the controls. In addition, reduced folate levels (p < 0.05) were observed in the PT group. A negative association of maternal plasma homocysteine with birth weight was seen in the idiopathic preterm group. Conclusions: Altered maternal micronutrients and resultant increased homocysteine concentrations exist in women delivering preterm. These alterations may also be partly associated with other factors such as undiagnosed inflammatory conditions or inadequate placentation in some women. Since these micronutrients play an important role in epigenetic regulation of vital genes involved in the fetal programming of adult diseases, further studies need to be undertaken to understand their role in preterm deliveries.     

Increased concentration of plasma homocysteine in children with systemic lupus erythematosus

OBJECTIVE: Studies in adults with SLE have evidenced increase of homocysteine related, mainly, to thromboembolic events. The aim of our study was to evaluate plasma homocysteine concentration in children with systemic lupus erythematosus (SLE) and its correlation with renal involvement, serum and erythrocyte folate, vitamin B12, antiphospholipid antibodies, estimated creatinine clearance and dyslipidemia. METHODS: Thirty-two children (29 females) with SLE and 32 healthy controls (29 females) matched for age and sex were included in the study. The mean age of patients and controls was 14.2 years (range from 10 to 18 years). Only one patient presented one thrombotic event. Plasma homocysteine, erythrocyte and serum folate, vitamin B12, lipid profile, antiphospholipid antibodies and estimated creatinine clearance were evaluated. Raised homocysteine concentration was defined as equal or more than 12.9 mol/L. RESULTS: Raised homocysteine concentration was detected in 15 (46.9%) children with SLE with an important statistical difference in relation to control group (p < 0.001). A positive correlation was found between plasma homocysteine concentration and renal involvement (odds ratio 11.1 [95% CI 1.50-82.24], p = 0.01) based on the presence of renal biopsy, abnormalities of urine sediment and/or serum creatinine. However, when we performed the estimated creatinine clearance the correlation with homocysteine concentration was not positive. We did not observe abnormalities in serum and erythrocyte folate and vitamin B12 in our patients. However, they presented significant higher concentrations of TC total cholesterol (p = 0.005) and of LDL low-density lipoprotein (p = 0.02) than controls. CONCLUSION: Elevated plasma homocysteine concentration is frequent in children with SLE. We believe that these results may signalize to the possibility of complications in our patients later in life. Further long-term and prospective studies are needed in order to determine the real role of the homocysteine concentration as a risk factor in children.     

同型半胱氨酸水平在急性脑梗死再发中的作用

目的 探讨血清同型半胱氨酸（homocysteine,Hcy）水平对脑梗死再发的影响.方法 选择急性脑梗死患者105例,健康对照组90例,比较两者的血清Hcy、叶酸及维生素B12水平;脑梗死组再随机分为A组和B组,A组给予抗血小板、他汀类及活血化瘀等药物,同时口服叶酸和甲钴胺;B组仅给予抗血小板、他汀类及活血化瘀等药物,随访12 m复查血清Hcy水平;观察治疗1年内脑梗死的再发情况.结果 （1）治疗前脑梗死组的Hcy水平显著高于健康对照组,其叶酸和维生素B12水平显著低于对照组（P＜0.001）;且脑梗死组的Hcy水平与叶酸、维生素B12水平呈负相关（P＜0.001）.（2）治疗前A、B两组Hcy水平无显著差异（P＞0.05）,治疗后两者Hcy水平有显著差异（P＜0.001）;A组治疗后Hcy水平显著低于治疗前（P＜0.001）;B组治疗前后Hcy水平无显著差异（P＞0.05）;（3）A组1年内脑梗死再发率为15.01％,B组为21.15％,两组比较差异无统计学意义（P＞0.05）.结论 高同型半胱氨酸血症是脑梗死的危险因素,给予叶酸和维生素B12治疗可有效降低脑梗死患者Hcy水平,但对脑梗死再发影响不大.     

Association of MTRR 66A>G polymorphism with superoxide dismutase and disease activity in patients with Crohn's disease

OBJECTIVES: The aim of this study was to evaluate the association of nutritional (folate, vitamin B12) and genetic (MTHFR, MTR, MTRR, TCN) determinants of homocysteine metabolism and of superoxide dismutase with Crohn's disease (CD). METHODS: One hundred forty patients with CD were compared with 248 matched healthy controls. RESULTS: Plasma homocysteine levels were higher in CD patients than controls (11.8 vs 10.4 micromol/L, P= 0.0004). Vitamin B12 and folate levels were lower in CD subjects compared to controls (207 vs 255 pmol/L, P= 0.0082, and 8.6 vs 11 nmol/L, P= 0036, respectively). Patients with a personal history of ileal resection, ileitis, or colectomy had significantly lower vitamin B12 levels. In multivariate analysis, vitamin B12 and MTHFR 677 TT carriers were the two significant independent factors of plasma homocysteine >15 micromol/L in CD patients (P= 0.0187 and 0.0048, respectively). The significant association between homocysteine and vitamin B12 levels remained significant only in patients with the highest superoxide dismutase values (P < 0.0001). The MTRR AA genotype was a significant independent predictor of CD risk (odds ratio 3.7, 95% CI 1.218-11.649, P= 0.0213). The level of superoxide dismutase was significantly higher (P= 0.0143) and was correlated with Crohn's Disease Activity Index (CDAI) scores (P for trend = 0.0276) in patients carrying MTRR AA genotype. CONCLUSIONS: Vitamin B12 and MTHFR 677 TT genotype are the main determinants of hyperhomocysteinemia in CD patients. The association of MTRR 66A>G polymorphism with oxidant stress and disease activity provides rationale for screening vitamin deficiencies in these patients.     

Elevated levels of homocysteine in plasma as a risk factor for coronary artery disease

This study was performed to assess the significance of association between coronary artery disease (CAD) and circulating homocysteine concentrations. 100 consecutive CAD patients (78 men and 22 women, aged 31 to 79 years) qualified for PTCA were investigated. At the time of PTCA, the risk factors for CAD and plasma for homocysteine and vitamins were obtained. The controls were without clinical evidence of coronary artery disease and hypertension (90 men and 30 women aged 32 to 81 years). Homocysteine was assayed using ELISA test. Red cell folate and plasma vitamin B12 were assayed by immunofluoroscency (Delphia test). Homocysteine concentrations were higher in patients than in controls (13.61 +/- 4.5 vs 10.99 +/- 4.49 mumol/L, p < 0.001, adjusted for age). Male patients had nonsignificantly higher homocysteine levels than females (13.94 +/- 5.21 vs 11.46 +/- 5.16 mumol/L, p = 0.05, adjusted for age). Elevated homocysteine level--defined as one in the top fifth of the control distribution > or = 12.83 mumol/L--was seen in 46% of the patients compared with 20% of the control group (p = 0.001). The odds ratio (OR) for CAD in persons with elevated homocysteine level was 3.1 (95% Cl 1.6-5.8, p < 0.001, adjusted for age). The OR for CAD of 5 mumol/L increment in homocysteine level was 2.1 (95% Cl 1.4-3.1 p < 0.001, adjusted for age). After adjustment for conventional risk factors (age, smoking, hypertension, family history of CAD, hyperlipidemia), elevated homocysteine level remained independent risk factor for CAD (OR 2.88, 95% Cl 1.1-7.8, p < 0.05). We observed inverse correlation between homocysteine and folate level (r = -0.32, p = 0.005) and between homocysteine and vitamin B12 concentrations (r = -0.24, p = 0.03), especially in men. Patients with elevated homocysteine level had lower levels of folate (629.6 +/- 241.2 nmol/L vs 735.1 +/- 252.4 nmol/L, p < 0.05), and vitamin B12 (213.6 +/- 64.4 pmol/L vs 246.6 +/- 62.3 pmol/L, p < 0.05) than patients with normal level of homocysteine. Elevated plasma homocysteine level is a strong risk factor for coronary artery disease. A 5 mumol/L increment in total homocysteine level may be associated with twofold increase of risk for the disease.     

Insulin sensitivity and plasma homocysteine concentrations in non-diabetic obese and normal weight subjects

OBJECTIVE: To determine whether plasma homocysteine (tHcy) levels were related to insulin resistance and obesity in subjects without diabetes or vascular disease. RESEARCH DESIGN AND METHODS: We studied correlates of plasma tHcy in 26 subjects covering a wide spectrum of obesity and insulin sensitivity (S(I)). The measurement of in vivo insulin sensitivity was performed using the minimal model analysis of the frequently sampled intravenous glucose tolerance test (FSIVGTT). RESULTS: There was no relationship between tHcy and body mass index. There was a significant relationship between plasma tHcy and S(I) (r=0.53, P=0.006), demonstrating that the more insulin sensitive subjects had higher levels of tHcy. On log transformation of the plasma insulin values, log insulin correlated negatively with plasma tHcy (r=-0.47; P=0.02). None of the subjects were deficient in vitamin B(12) and folate. Plasma vitamin B(12) was significantly related to plasma tHcy (r=-0.44, P=0.017), although we found no significant relationship between plasma folate and tHcy (r=-0.21, P=0.27). S(I) correlated significantly with vitamin B(12) (r=0.4, P=0.045) whereas, we found no significant relationship between S(I) and plasma folate (r=0.27, P=0.2). On multiple linear regression using tHcy as the dependent variable, S(I) and vitamin B(12) remained significant predictors of plasma tHcy, whereas, age and plasma folate were not predictors of tHcy. CONCLUSIONS: We conclude that in vitamin replete lean and obese individuals, insulin sensitivity correlates significantly with plasma tHcy. This relationship may need to be considered when evaluating the role of plasma homocysteine as a risk factor in patients with obesity and type 2 diabetes.     

Terminal ileum resection is associated with higher plasma homocysteine levels in Crohn's disease

BACKGROUND: Elevated plasma total homocysteine (tHcy) is associated with a higher risk of thrombosis. Crohn's disease (CD) is associated with hypercoagulability of undefined etiology. We investigated tHcy in patients with CD and its relationship with vitamin status, disease activity, location, duration, and history of terminal ileum (TI) resection. STUDY: We examined fasting plasma tHcy, folate, serum vitamin B12 levels, and sedimentation rate in consecutive adult patients with CD. Harvey-Bradshaw index of CD activity and history of TI resection and thromboembolism were recorded. RESULTS: Median plasma tHcy was 10.2 micromol/L in 125 patients with CD. Men (n = 60) had higher plasma tHcy than women (n = 65) (11.2 vs. 9.1 micromol/L; p = 0.004). Patients with a history of TI resection showed lower serum B12 levels (293 vs. 503 pg/mL; p < 0.001) and higher plasma tHcy levels (11.0 vs. 9.35 micromol/L; p = 0.027) than patients without such history. Multivariate analysis showed history of TI resection, serum B12, and creatinine levels to be significant predictors of elevated plasma tHcy. Fourteen patients with CD with a history of thrombosis had an elevated median plasma tHcy of 11.6 micromol/L. CONCLUSIONS: Terminal ileum resection contributes to elevated plasma tHcy levels in CD cases. We recommend tHcy screening in patients with CD, especially in those with prior history of TI resection, and the initiation of vitamin supplementation when appropriate.