Myeloperoxidase gene-463G > A polymorphism and premature coronary artery disease

We investigated the association between myeloperoxidase gene -463G > A polymorphism and premature coronary artery disease (CAD) in two Chinese population samples: 229 patients and 230 controls. Genotypes were determined by ligase detection reaction-polymerase chain reaction sequencing and the grouping technique. We found lower frequencies of both the A/A genotype and the A allele in patients (p < 0.05). Multivariate logistic regression showed that the risk of premature CAD in subjects carrying the AA genotype was reduced by 83% in relation to individuals carrying the G/G genotype (OR = 0.172, 95% CI: 0.057-0.526, p = 0.002). Our results indicate that -463G > A polymorphism of the myeloperoxidase gene is associated with premature CAD in Chinese individuals, suggesting that the AA genotype is a protective factor against premature CAD

Hyperhomocysteinaemia is associated with coronary events in type 2 diabetes

Objectives. Amongst nondiabetic individuals, a high serum homocysteine concentration is an independent but relatively weak risk factor for coronary events. However, it is not known whether homocysteine increases risk of coronary events in type 2 diabetes. Therefore, we examined the combined effect of homocysteine and type 2 diabetes on risk of fatal and nonfatal coronary events. Subjects. We assessed the 10-year risk of coronary events associated with homocysteine amongst diabetic (n = 140) and nondiabetic (n = 361) individuals. Design. We did this in the Hoorn Study, a population-based study of glucose tolerance and related complications in Caucasian men and women aged 50-75 years. Results. The incidence rate for coronary events was 2.63 (29 of 140) per 100 person-years amongst diabetic and 1.29 (42 of 361) amongst nondiabetic individuals. Amongst diabetic individuals, risk of coronary events increased 28% for each 5-μmol

Homocysteine and Familial Longevity: The Leiden Longevity Study

Homocysteine concentrations are a read-out of methionine metabolism and have been related to changes in lifespan in animal models. In humans, high homocysteine concentrations are an important predictor of age related disease. We aimed to explore the association of homocysteine with familial longevity by testing whether homocysteine is lower in individuals that are genetically enriched for longevity. We measured concentrations of total homocysteine in 1907 subjects from the Leiden Longevity Study consisting of 1309 offspring of nonagenarian siblings, who are enriched with familial factors promoting longevity, and 598 partners thereof as population controls. We found that homocysteine was related to age, creatinine, folate, vitamin B levels and medical history of hypertension and stroke in both groups (all p<0.001). However, levels of homocysteine did not differ between offspring enriched for longevity and their partners, and no differences in the age-related rise in homocysteine levels were found between groups (p for interaction 0.63). The results suggest that homocysteine metabolism is not likely to predict familial longevity

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and high plasma homocysteine in chronic hepatitis C (CHC) infected patients from the Northeast of Brazil

<p>Abstract</p> <p>Background/Aim</p> <p>Hyperhomocysteinemia due to Methylenetetrahydrofolate Reductase (<it>MTHFR</it>) gene, in particular the C677T (Ala222Val) polymorphism were recently associated to steatosis and fibrosis. We analyzed the frequency of <it>MTHFR </it>gene in a cross-sectional study of patients affected by Chronic Hepatitis C (CHC) from Northeast of Brazil.</p> <p>Method</p> <p>One hundred seven-four untreated patients with CHC were genotyped for the C677T <it>MTHFR</it>. Genomic DNA was extracted from peripheral blood cells and the C677T <it>MTHFR </it>polymorphism was identified by PCR-RFLP. The homocysteine (Hcy) levels were determined by chemiluminescence method. All patients were negative for markers of Wilson's disease, hemochromatosis and autoimmune diseases and have current and past daily alcohol intake less than 100 g/week.</p> <p>Results</p> <p>Among subjects infected with CHC genotype non-1 the frequency of <it>MTHFR </it>genotypes TT was 9.8% <it>versus </it>4.4% genotype 1 (p = 0.01). Nevertheless, association was found between the <it>MTHFR </it>genotype TT × CT/CC polymorphism and the degree of steatosis and fibrosis in both hepatitis C genotype (p < 0.05). A significant difference was found on plasma Hcy levels in patients with steatosis regardless of HCV genotype (p = 0.03).</p> <p>Conclusion</p> <p>Our results indicate that plasma Hcy levels is highly prevalent in subjects with chronic hepatits C with steatosis regardless of HCV genotype and vitamin deficiency. The presence of genotype TT of <it>MTHFR </it>C677T polymorphism was more common in CHC genotype non-1 infected patient regardless of histopathological classification and genotype TT+CT frequencies were significant in the presence of fibrosis grade 1+2 and of steatosis in CHC infected patients from the northeast of Brazil regardless of HCV genotype. The genetic susceptibility of <it>MTHFR </it>C677T polymorphism should be confirmed in a large population.</p

Preliminary Evidence for Cell Membrane Amelioration in Children with Cystic Fibrosis by 5-MTHF and Vitamin B12 Supplementation: A Single Arm Trial

Cystic fibrosis (CF) is one of the most common fatal autosomal recessive disorders in the Caucasian population caused by mutations of gene for the cystic fibrosis transmembrane conductance regulator (CFTR). New experimental therapeutic strategies for CF propose a diet supplementation to affect the plasma membrane fluidity and to modulate amplified inflammatory response. The objective of this study was to evaluate the efficacy of 5-methyltetrahydrofolate (5-MTHF) and vitamin B12 supplementation for ameliorating cell plasma membrane features in pediatric patients with cystic fibrosis.A single arm trial was conducted from April 2004 to March 2006 in an Italian CF care centre. 31 children with CF aged from 3 to 8 years old were enrolled. Exclusion criteria were diabetes, chronic infections of the airways and regular antibiotics intake. Children with CF were supplemented for 24 weeks with 5-methyltetrahydrofolate (5-MTHF, 7.5 mg /day) and vitamin B12 (0.5 mg/day). Red blood cells (RBCs) were used to investigate plasma membrane, since RBCs share lipid, protein composition and organization with other cell types. We evaluated RBCs membrane lipid composition, membrane protein oxidative damage, cation content, cation transport pathways, plasma and RBCs folate levels and plasma homocysteine levels at baseline and after 24 weeks of 5-MTHF and vitamin B12 supplementation. In CF children, 5-MTHF and vitamin B12 supplementation (i) increased plasma and RBC folate levels; (ii) decreased plasma homocysteine levels; (iii) modified RBC membrane phospholipid fatty acid composition; (iv) increased RBC K(+) content; (v) reduced RBC membrane oxidative damage and HSP70 membrane association.5-MTHF and vitamin B12 supplementation might ameliorate RBC membrane features of children with CF.ClinicalTrials.gov NCT00730509