Objective To investigate the association between total homocysteine (tHcy) level in plasma and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus (T2DM) accompanied by dyslipidemia. Methods This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively. Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of MTHFR C677T and A1298C. Plasma tHcy and lipid levels were measured as well. The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using Chi-square test. Plasma tHcy level of T2DM patients who carried the different genotypes was compared by Student's t test. Results Finally, 82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study. There was a significant correlation between tHcy level and MTHFR C677T gene polymorphism in T2DM patients (t=2.27, P=0.02). Moreover, the plasma tHcy level in the dyslipidemia patients who carried MTHFR 677 TT genotype was significantly higher than that in those with CT+CC genotype (13.62±6.97 vs. 10.95±3.62 μmol/L, t=2.20, P=0.03); while for patients without dyslipidemia, comparison of the tHcy level between those who carried the above two alleles showed no significantly difference (13.34±6.03 vs. 12.04±5.09 μmol/L, t=1.08, P=0.29). Conclusion MTHFR 677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.
Adult ; Aged ; Alleles ; Asian People/genetics* ; Base Sequence ; Case-Control Studies ; China ; Diabetes Mellitus, Type 2/genetics* ; Dyslipidemias/genetics* ; Gene Frequency ; Genotype ; Homocysteine/blood* ; Humans ; Linkage Disequilibrium ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Middle Aged ; Polymorphism, Single Nucleotide

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

BACKGROUND: Currently, the hypertension (HTN) patients undergo appropriate medical treatment, and traditional risk factors are highly controlled. Therefore, potential risk factors of atherosclerotic vascular diseases (AVD) and venous thromboembolisms (VTE) in HTN should be reconsidered. We investigated thrombophilic genetic mutations and existing biomarkers for AVD or VTE in HTN patients receiving treatment. METHODS: A total of 183 patients were enrolled: AVD with HTN (group A, n=45), VTE with HTN (group B, n=62), and HTN patients without any vascular diseases (group C, n=76). The lipid profile, homocysteine (Hcy) levels, D-dimers, fibrinogen, antithrombin, lupus anticoagulant, and anti-cardiolipin antibody (aCL) were evaluated. Prothrombin G20210A, Factor V G1691A, and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C were analyzed. RESULTS: All patients revealed wild type prothrombin G20210A and Factor V G1691A polymorphisms. The frequency of MTHFR polymorphisms was 677CT (n=84, 45.9%); 677TT (n=46, 25.1%); 1298AC (n=46, 25.1%); and 1298CC (n=2, 1.1%). The MTHFR 677TT genotype tended to increase the odds ratio (OR) to AVD events in HTN patients (OR 2.648, confidence interval 0.982-7.143, P=0.05). The group A demonstrated significantly higher Hcy levels (P=0.009), fibrinogen (P=0.004), and platelet counts (P=0.04) than group C. Group B had significantly higher levels of D-dimers (P=0.0001), platelet count (P=0.0002), and aCL (P=0.02) frequency than group C. CONCLUSIONS: The MTHFR 677TT genotype and Hcy level could be potential risk factors associated with development of AVD in HTN patients receiving treatment. D-dimer and aCL might be useful to estimate the occurrence of VTE in them.
Adult ; Aged ; Antihypertensive Agents/therapeutic use ; DNA/analysis ; Factor V/genetics ; Female ; Fibrin Fibrinogen Degradation Products/analysis ; Genotype ; Homocysteine/blood ; Humans ; Hypertension/*complications/drug therapy ; Lipids/blood ; Male ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics ; Middle Aged ; Odds Ratio ; Platelet Count ; Polymorphism, Single Nucleotide ; Prothrombin/genetics ; Real-Time Polymerase Chain Reaction ; Republic of Korea ; Risk Factors ; Vascular Diseases/*etiology/genetics ; Venous Thrombosis/*etiology/genetics

OBJECTIVETo assess the association of plasma homocysteine (Hcy) level and 66A/G and 524C/T polymorphisms of methionine synthase reductase (MSR) gene with essential hypertension (EH) in ethnic Uygurs and Hans from Xinjiang.

METHODSFrom September 2011 to July 2014, 199 Uyghur and 216 Han patients were collected, while 195 healthy Uyghur ethnics and 217 healthy Han ethnics were recruited as the controls. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RELP) was adopted to detect the above polymorphisms. Enzyme immunological assay was applied to measure the levels of plasma Hcy.

RESULTSCompared with the control, plasma Hcy levels were significantly higher in EH group in both Uyghur and Han ethnics (P<0.05). In both ethnic groups, there were also significant differences in MSR 524C/T polymorphism between the patients and controls (Uyghur: chi-square=6.559, P=0.038; Han: chi-square=12.684, P=0.002). No significant difference was found in MSR 66A/G polymorphism between the patients and controls in both ethnic groups (P>0.05). Plasma Hcy level in those with a 66G/524C genotype was statistically higher than that with 66A/524T (P<0.05). After adjusting confounding factors such as gender and age, Logistic regression analysis indicated that age (OR=1.924, 95% CI:1.177- 3.164, P=0.009), obesity (OR=2.491, 95% CI: 1.584-3.920, P<0.01), hyperhomocysteine (OR=1.609, 95% CI: 1.016-2.548, P=0.043) were independent risk factors for EH in Uygurs, while age (OR=1.133, 95% CI: 1.010-81.272, P=0.033), hyperhomocysteine level (OR=3.894, 95% CI: 2.432-6.237, P<0.01), and obesity (OR=1.864, 95% CI: 1.141-3.046, P=0.013) were independent risk factors for EH in Han ethnics. No association was found between the polymorphisms and EH in Uygurs and Hans.

CONCLUSIONAge, hyperhomocysteine and obesity were common independent risk factors for EH in both Uygur and Han ethnics from Xinjiang. The MSR 66G genotype can increase the plasma concentration of Hcy, while MSR 524T genotype may reduce it. MSR 524C/T TT genotype may be a protective factor for EH. MSR polymorphisms 66A/G and 524C/T are not independent risk factors for EH in Uygur and Han ethnics from Xinjiang.

Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; China ; ethnology ; Essential Hypertension ; Female ; Ferredoxin-NADP Reductase ; genetics ; metabolism ; Homocysteine ; blood ; Humans ; Hypertension ; blood ; enzymology ; ethnology ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

OBJECTIVETo investigate the cystathione beta synthase (CBS) gene T833C, G919A, 844ins68 polymorphisms and plasma homocysteine (Hcy) levels in ethnic Uyghur and Han patients with essential hypertension (EH) in Xinjiang.

METHODSFour hundred twenty nine cases including 211 Uyghur and 218 Han EH patients were recruited, whilst 410 healthy individuals including 210 Uyghurs and 200 Hans were used as the controls. Amplification refractory mutation system (ARMS) was adopted to analyze the CBS gene polymorphisms including T833C, G919A and 844ins68. Enzymoimmunoassay was applied to determine the plasma level of Hcy. Chemiluminescence was applied to determine the plasma folic acid and vitamin B12.

RESULTSCompared with the controls, the plasma Hcy level was significantly higher in the EH group in both ethnic Uyghurs and Hans (P < 0.05). Plasma levels of Hcy in T833C, G919A genotypes (for both heterozygotes and homozygotes) were statistically higher than wild types (P < 0.05). A significant difference was detected in G919A polymorphism between the EH patients and controls in both Uyghur and [CM(144.5mm] Han ethnics (Uyghur: x² = 10.264, P < 0.01; Han: x² = 23.075, P < 0.01), and in T833C between the EH patients and controls in ethnic Uyghurs (x² = 40.254, P < 0.01). Logistic regression analysis indicated that age (OR=1.151, P=0.047, 95% CI = 1.002-1.323), T833C (CC) (OR = 1.078, P = 0.003, 95% CI = 1.043-1.114), obesity (OR = 1.284, P = 0.021, 95% CI = 1.038-1.590), hyperhomocysteine (OR = 3.296, P = 0.016, 95% CI = 1.244-8.733) were independent risk factors for EH among ethnic Uygurs, while age (OR = 1.162, P = 0.007, 95% CI = 1.042-1.297), obesity (OR = 3.501, P = 0.003, 95% CI = 1.521-8.060), hyperhomocysteine (OR = 1.046, P = 0.031, 95% CI = 1.011-1.459) were independent risk factors for EH in ethnic Hans after adjusting for confounding factors.

CONCLUSIONPlasma level of Hcy is associated with ethnic Uyghur and Han patients with EH in Xinjiang. CBS gene T833C CC genotype may be associated with the EH among Uyghur ethnics.

Adult ; Aged ; China ; ethnology ; Cystathionine beta-Synthase ; genetics ; Essential Hypertension ; Female ; Gene-Environment Interaction ; Homocysteine ; blood ; Humans ; Hypertension ; genetics ; Logistic Models ; Male ; Middle Aged ; Polymorphism, Genetic

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

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

The reference interval for plasma total homocysteine (tHcy) and serum folate concentrations were estimated. Total of 3,154 reference individuals (1,029 men and 2,125 women) were selected based on stringent exclusion criteria. For plasma tHcy concentration (microM/L), reference values (median [5-95 percentile]) were 7.72 (5.03 to 13.80) and 6.09 (3.95-10.19) in men and women, respectively. For serum folate concentration (nM/L), reference values were 23.71 (11.73-38.44) and 28.95 (15.23-40.44) in men and women, respectively. The tHcy levels of both genders in the present study were lower than those in previous reports from other countries and Korea.
Age Factors ; Aged ; Aging ; Cohort Studies ; Female ; Folic Acid/*blood ; Genotype ; Homocysteine/*blood ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2)/*genetics ; Middle Aged ; Reference Values ; Republic of Korea ; Sex Factors

Adult ; Age of Onset ; Amino Acid Metabolism, Inborn Errors ; complications ; diagnosis ; genetics ; therapy ; Betaine ; administration & dosage ; therapeutic use ; Carrier Proteins ; genetics ; metabolism ; Child ; China ; epidemiology ; DNA Mutational Analysis ; Gas Chromatography-Mass Spectrometry ; Genotype ; Homocysteine ; urine ; Humans ; Hydroxocobalamin ; administration & dosage ; therapeutic use ; Hyperhomocysteinemia ; complications ; diagnosis ; genetics ; therapy ; Infant ; Methylmalonic Acid ; blood ; urine ; Mutation ; Vitamin B 12 ; metabolism

OBJECTIVETo explore the distribution of genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) 677C/T, 1298A/C and methionine synthase reductase (MTRR) 66A/G among ethnic Han females from Linyi, and to correlate it with serum level of homocysteine (Hcy).

METHODSA cross-sectional study was carried out. Oral epithelial cell samples were collected from 825 subjects. MTHFR and MTRR gene polymorphisms were determined with a Taqman-Minor Groove Binder (MGB) method. Distribution of gene polymorphisms was analyzed and compared with others regions of China including Weifang, Zhengzhou, Deyang and Hainan. A biochemical assay was also carried out to determine the total Hcy in plasma of 281 subjects. The reductase activity of MTHFR was classified into decreased and stable groups according to genetic polymorphism of MTHFR. Correlation between MTHFR groups and total Hcy level were also explored.

RESULTS(1) The frequencies of MTHFR677CC, CT and TT genotypes of the selected subjects were 16.7%, 48.3% and 35.0%, respectively. The frequencies of MTHFR 1298AA, AC and CC genotypes were 76.0%, 21.6% and 2.4%, respectively. And those of MTRR 66AA, AG and GG genotypes were 54.7%, 39.4% and 5.9%, respectively. For the selected subjects, their frequency of MTHFR 677TT genotype was higher than that of Deyang and Hainan (P< 0.01), whilst the frequency of MTHFR 1298CC genotype was lower than that of Deyang and Hainan (P < 0.01), and the frequency of MTRR 66 GG genotype was lower than that of Hainan (P< 0.01). (2) The Hcy level for those with decreased MTHFR activity was significantly higher than those with stable MTHFR activity (P< 0.05).

CONCLUSIONMTHFR gene 677C/T, 1298A/C and MTRR 66A/G polymorphisms in ethnic Han women from Linyi have differed significantly from other regions of China. Decreased MTHFR activity caused by genetic polymorphisms is a risk factor for raised Hcy level.

Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; China ; Female ; Ferredoxin-NADP Reductase ; genetics ; Gene Frequency ; Genetic Association Studies ; Genotype ; Homocysteine ; blood ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2) ; blood ; genetics ; Polymorphism, Single Nucleotide ; Young Adult