OBJECTIVETo investigate the changes of plasma homocysteine (Hcy) level in patients with ischemic cerebrovascular or cardiovascular disease and analyze the relationship between plasma Hcy levels and the mutations in Hcy metabolism related enzymes, including methylene tetrahydrofolate reductase (MTHFR) C677T, cystathionine beta-synthetase (CBS) 844ins68 and methionine synthetase (MS) A2756G.

METHODSBy using the HPLC-FLD method, the plasma total homocysteine (tHcy) concentration was determined in 86 patients with cerebral infarction, 66 with myocardial infarction and 80 healthy controls. The association of plasma tHcy levels with cardiovascular or cerebrovascular disease and mutations of MTHFR C677T, CBS 844 ins 68 and MS A2756G were evaluated by statistic methods.

RESULTSIn the patient groups, the plasma tHcy concentrations increased significantly as compared with healthy controls. The individuals homozygous for MTHFR C677T mutation had significantly higher plasma Hcy levels.

CONCLUSIONHyperhomocysteinemia is an important risk factor for ischemic cerebrovascular and cardiovascular disease. The homozygosity of MTHFR C677T may contribute to the increase of plasma Hcy and vascular damage.

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ; genetics ; Brain Ischemia ; blood ; genetics ; Cystathionine beta-Synthase ; genetics ; Female ; Heterozygote ; Homocysteine ; blood ; Homozygote ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; Middle Aged ; Mutation ; Myocardial Ischemia ; blood ; genetics ; Oxidoreductases Acting on CH-NH Group Donors ; genetics ; Polymorphism, Genetic

OBJECTIVETo study the relationship between the plasma homocysteine (HCY) level and the polymorphism of N(5), N(10)-methylenetetrahydrofolate reductase (MTHFR) gene C667T in liver cirrhosis.

METHODS112 normal subjects and 87 liver cirrhosis patients were recruited in the study. Their plasma HCY levels were measured using high performance liquid chromatography with fluorescence detection and polymorphisms of their MTHFR gene were analyzed using PCR-RFLP.

RESULTSThe mean level of plasma HCY was significantly higher in patients with liver cirrhosis (21.71+/-4.86) micromol/L than that in healthy individuals (8.34+/-3.59) micromol/L. There were three kinds of MTHFR genotypes: +/+ (TT, homozygous mutation), +/- (CT, heterozygous mutation) and -/- (CC, wild type). The frequencies of the three genotypes were as follows: +/+, 29.9%; +/-, 52.9%; -/-, 17.2% in cirrhosis patients and +/+, 19.6%; +/-, 33.9%; -/-, 46.4% in normal subjects. The frequency of homozygous or heterozygous mutation was significantly higher in cirrhosis patients than that in the normal control. Moreover, plasma homocysteine level was markedly higher in patients with MTHFR genetic mutation than those without mutation.

CONCLUSIONSHyperhomocysteinemia may be an independent risk factor for liver cirrhosis. MTHFR is the main enzyme related to homocysteine metabolism. The genetic mutation of MTHFR C667T is possibly an important mechanism of hyperhomocysteinemia in liver cirrhosis. The level of plasma homocysteine may be an early indicator for liver cirrhosis.

Female ; Homocysteine ; blood ; Humans ; Hyperhomocysteinemia ; complications ; genetics ; Liver Cirrhosis ; complications ; genetics ; Male ; Methylenetetrahydrofolate Dehydrogenase (NAD+) ; genetics ; Point Mutation ; Polymorphism, Genetic

Hyperhomocysteinemia is known to be associated with an increased risk of myocardial infarction, stroke, peripheral arterial disease, and venous thrombosis. Gene polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) may account for reduced enzyme activity and hyperhomocysteinemia. A recent study has documented evidence of polygenic regulation of plasma homocyteine. We report here on a case of occlusive stroke at young age and hyperhomocysteinemia with homozygous VN (677C to T) variant in the MTHFR gene as well as homozygous D/D (2756G to A) variant in the MS gene.
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase/*genetics ; Adult ; Cerebrovascular Accident/*genetics ; DNA/metabolism ; DNA Restriction Enzymes/metabolism ; Family Health ; Female ; Genotype ; Homocysteine/blood/genetics ; *Homozygote ; Human ; Hyperhomocysteinemia/*genetics ; Male ; Polymorphism (Genetics) ; Tetrahydrofolates/*genetics ; Variation (Genetics)

OBJECTIVETo assess the association of transcobalamine II (TCN2) gene polymorphisms and serum levels of homocysteine (Hcy), vitamin Band folate with ulcerative colitis (UC) among Chinese patients.

METHODSFor 397 UC patients and 574 controls, two single nucleotide polymorphisms of the TCN2 gene (rs1801198, rs9606756) were tested with an improved multiple ligase detection reaction method. Serum Hcy, vitamin Band folate were measured with an enzymatic cycling assay and an chemiluminescence immunoassay, respectively.

RESULTSThe allelic and genotypic frequencies of rs1801198 and rs9606756 did not differ significantly between the two groups (all P> 0.05). Compared with those of the control group, the frequencies of G allele and CG+GG genotype of rs1801198 were greater in patients with moderate and severe UC (both P< 0.05). The same conclusion may also be drawn for the G allele and AG genotype of rs9606756 (both P< 0.05). Compared with the controls, average Hcy level was enhanced in UC patients (P< 0.01), whereas average vitamin Band folate levels were decreased in UC patients (both P< 0.01). In both groups, the average level of Hcy was lower in individuals carrying CC of (rs1801198) than in those with CG+GG (both P< 0.05). A similar conclusion was also drawn for individuals with AA of rs9606756 when compared with those carrying AG(both P< 0.05). Compared with patients with mild UC, average Hcy level was increased in those with moderate and severe UC (P< 0.01), while average vitamin Band folate levels were decreased in those with moderate and severe UC (both P< 0.01). The prevalence of hyperhomocysteinemia(HHcy), vitamin Bdeficiency and folate deficiency was greater in UC patients than in controls (all P< 0.01). In UC patients, the level of Hcy was negatively correlated with those of vitamin B(P< 0.01), albumin(P< 0.01), red blood cells(P< 0.01) and platelet (P< 0.05), but positively correlated with white blood cells(P< 0.01) and Mayo score (P< 0.01). Both HHcy and folate deficiency were independent risk factors for UC (OR=4.173, OR=5.206, both P< 0.01).

CONCLUSIONTCN2 (rs1801198, rs9606756) variations, as well as serum levels of Hcy, vitamin Band folate, are correlated with UC. Both HHcy and folate deficiency are independent risk factors for UC.

Adult ; Colitis, Ulcerative ; blood ; etiology ; genetics ; Female ; Folic Acid ; blood ; Genotype ; Homocysteine ; blood ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Transcobalamins ; genetics ; Vitamin B 12 ; blood

OBJECTIVEThe effect of the gene polymorphism for the key enzyme's folacin metabolism pathway on plasmatic homocysteine (Hcy) levels in fertile woman was observed.

METHODSThe subjects were from Shaoxing City, Jiangsu province in 2012, the selection criteria for the women of childbearing age were between 20-45 years old, with an average age of 28.2 (95%CI:27.8-28.6) years old. Sample collection continued uninterrupted lasted seven days, a total of 535 samples were collected, venous blood with EDTA addition or sodium citrate to anticoagulant. After separation, the blood cells and blood plasma were cryopreserved. DNA was extracted using spin column method. All the samples were selected for the gene polymorphism testing of the key enzyme's on folate metabolism and monitoring of plasmatic Hcy level.

RESULTSEight single nucleotide polymorphism (SNP) sites of methylenetetrahydrofolate reductase gene (MTHFR) , methionine synthase gene (MS) , synthetic methionine reductase gene (MSR) and cystathionine β synthase gene (CBS) were detected. It was found the genotype AA of the SNP sites-rs1801131 would result higher plasmatic Hcy levels (8.99 µmol/L) than the genotypes CC (7.81 µmol/L) and CA(8.38 µmol/L) (P < 0.01) . Similarly, the genotype TT of the SNP sites-rs1801133 was significantly responded to the increasing of Hcy levels (11.10 µmol/L) than the genotype CC (8.15 µmol/L) and CT (8.45 µmol/L), (P < 0.01) . The two sites of genotype combination of AA-TT could also result in the significant increase of Hcy levels (11.02 µmol/L) than other combined genotypes (genotypes CC-CC, CA-CC, CA-CT, AA-CC, AA-CT), especially the genotype CC-CC. And the risk factor was 1.41 (95CI:1.20-1.66) times over the genotype CC-CC.

CONCLUSIONThe gene mutations of two SNP sites rs1801131 and rs1801133 in MTHFR would increase Hcy levels.

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ; genetics ; Adult ; China ; Cystathionine beta-Synthase ; genetics ; Female ; Ferredoxin-NADP Reductase ; genetics ; Folic Acid ; Genotype ; Homocysteine ; blood ; genetics ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Mutation ; physiology ; Polymorphism, Single Nucleotide ; Risk Factors

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ; genetics ; Carrier Proteins ; genetics ; Congenital Abnormalities ; etiology ; Folate Receptors, GPI-Anchored ; Folic Acid Deficiency ; complications ; etiology ; Homocysteine ; blood ; Humans ; Membrane Transport Proteins ; genetics ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Receptors, Cell Surface ; genetics

OBJECTIVETo investigate the relationship between paraoxonase (PON) polymorphisms and serum homocysteine thiolactone (HTL) and coronary heart diseases.

METHODIn this prospective study, serum complex of HTL levels using ELISA, and the lever of serum Hcy using high pressure liquid chromatography (HPLC), determined the PON1/T(-107)C and PON2/C311S genotypes using PCR-restriction fragment length polymorphisms 203 were measured in patients with angiographic documented coronary heart disease (CAD) and 117 controls.

RESULTSSerum levels of Hcy and the complex of HTL in CAD patients were significantly higher than that in controls (P < 0.05). No significant difference was found in frequencies of PON1/T(-107)C genotypes and alleles (P > 0.05) between CAD patient and controls. The PON2/C311S (SS) genotype was lower in CAD patients than that in controls (P < 0.05), while the frequency of allele was similar between the two groups (P > 0.05). The T allele of PON1/T(-107)C and S alleles of PON2/C311S polymorphism were associated with lower plasma Hcy and HTL complex [Hcy (11.83 +/- 4.76) micromol/L vs (15.32 +/- 10.32) micromol/L, P < 0.05; HTL complex (24.36 +/- 9.30) U/ml vs (32.05 +/- 10.44) U/ml, P < 0.05]. The genetype PON2 and allele C were higher in CAD patients with type 2 diabetes than that in CAD patients without type 2 diabetes and controls (P < 0.005).

CONCLUSIONSThe elevation of serum Hcy and the complex of HTL were associated with increased risk of coronary heart disease. The allele PON1/(-107)T and PON2/311S might be protective for the development of atherosclerosis.

Adult ; Aged ; Aryldialkylphosphatase ; genetics ; Coronary Disease ; blood ; complications ; genetics ; Cysteine ; blood ; Diabetes Mellitus, Type 2 ; complications ; Female ; Homocysteine ; analogs & derivatives ; blood ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic

OBJECTIVETo study the relationship between plasma homocysteine (Hcy) level and deep-vein thrombosis (DVT), and analyze the interaction of Hcy, folate and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in patients with DVT.

METHODSTotally 69 patients with DVT and 111 healthy controls were included in our case-control study. We determined the MTHFR C677T genotypes by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), measured the serum folate and vitamin B12 by radioimmunoassay (RIA), and measured the plasma homocysteine level by fluorescence polarization immunoassay (FPIA).

RESULTSThe frequency of the MTHFR C677T TT genotype had no significant difference between DVT group and control group (P > 0.05). The plasma Hcy level was significantly higher in DVT group than in control group (13.03 +/- 8.74 mumol/L vs 10.14 +/- 4.30 mumol/L, P < 0.05). Both serum folate and VitB12 of patients with DVT were not significantly different from those of controls. The odds radios (OR) of hyperhomocysteinemia for DVT was 2.53 (95% CI 1.08-5.92). The interaction of low folate level and TT genotype increased the risk of DVT (OR = 3.12, 95% CI 1.17-8.38).

CONCLUSIONHyperhomocysteinemia may be an independent risk factor for DVT in Han nationality, while serum folate level and MTHRF C677T genotype are not. An interaction between serum folate level and MTHFR genotype that affect the Hcy level is an important risk factor for DVT.

Adult ; Aged ; Aged, 80 and over ; Female ; Folic Acid ; blood ; Genetic Predisposition to Disease ; Homocysteine ; blood ; genetics ; Humans ; Hyperhomocysteinemia ; blood ; genetics ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Middle Aged ; Polymorphism, Restriction Fragment Length ; Venous Thrombosis ; blood ; etiology ; genetics ; Vitamin B 12 ; blood

OBJECTIVETo study the association of methylenetetrahydrofolate reductase (MTHFR) gene C677T mutation and plasma homocysteine (Hcy) levels with hyperlipidemia.

METHODSBlood samples were collected from 1591 adults for detecting MTHFR gene C677T polymorphism with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), plasma Hcy levels with enzymatic cycling method, and blood lipid levels as well. The patients were divided according to the lipid levels into hyperlipidemia group (n=694) and healthy control group (n=897) and the differences in MTHFR gene C677T polymorphisms and plasma Hcy levels were compared.

RESULTSThe hyperlipidemia group and healthy control group showed no significant differences in CC, CT, or TT genotype frequencies or C and T allele frequencies of MTHFR C677T gene, and had comparable plasma Hcy levels (P>0.05). Patients with 3 different MTHFR C677T genotypes had significant differences in plasma Hcy levels (P<0.01) but not in blood lipid levels (P>0.05). Pairwise comparison indicated a significantly higher plasma Hcy level in TT genotype than in CC and CT genotypes (P<0.01), and the latter two genotypes showed no significant difference (P>0.05).

CONCLUSIONMTHFR C677T polymorphisms and plasma Hcy levels are closely related but neither of them is associated with hyperlipidemia. The TT genotype is associated with a significantly higher plasma Hcy level than CC and CT genotypes.

Adult ; Gene Frequency ; Genotype ; Homocysteine ; blood ; Humans ; Hyperlipidemias ; blood ; genetics ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Mutation ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length

OBJECTIVETo investigate the relationship of plasma homocysteine (Hcy) level to stroke and genetic factor to elevated plasma Hcy level.

METHODSThe plasma Hcy level was measured by capillary electrophoresis-ultraviolet detection and the gene polymorphism of N5,N10-methylenetetrahydrofolate reductase (MTHFR) was studied with PCR-RFLP assay in 43 patients with cortical cerebral infarction and 42 healthy control.

RESULTSThe plasma Hcy level of the patients (19.3 +/- 6.0 micromol/L) was markedly higher than that of the controls (13.7 +/- 5.4 micromol/L) (t = 4.16, P < 0.001). There are 3 genotypes, C/C, C/T and T/T, about base-variation of MTHFR gene at locus 677. The plasma Hcy level of the subjects with T/T genotype was higher than that of subjects with other genotypes. However, the frequencies of each genotype and allele were not significantly different between the patients and the controls.

CONCLUSIONSThe elevated plasma Hcy level is a risk factor for atherothrombotic cerebral infarction, and is related to the C-->T mutation at locus 677 of MTHFR gene.

Aged ; Cerebral Infarction ; blood ; genetics ; Female ; Gene Frequency ; Genotype ; Homocysteine ; blood ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Middle Aged ; Point Mutation ; Polymorphism, Genetic