• Journal of Nutrition and Health
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• v.43 no.5
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• pp.443-452
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• 2010

Elevated plasma concentration of total homocysteine (ptHcy) is known as an independent risk factor of cardiovascular disease (CVD) and oxidative stress is also commonly implicated in CVD. An association between ptHcy and oxidative stress has recently been suggested. The study objective is to examine the relationship between ptHcy and oxidative stress markers in 103 healthy college students (62 males and 41 females). Plasma levels of ptHcy, oxidative stress markers (conjugated diene, erythrocyte catalase, TRAP, lymphocyte DNA damage), antioxidant vitamins ($\alpha$-tocopherol, $\gamma$-tocopherol, carotenoids), and lipid parameters (total cholesterol, triglyceride, HDL cholesterol) were determined. The results show that the concentration of ptHcy was significantly higher in male subjects ($22.17\;{\pm}\;2.14\;{\mu}mole/L$) than in female subjects ($12.28\;{\pm}\;0.45\;{\mu}mole/L$). There was a negative association between ptHcy and plasma ${\beta}$-carotene in male subjects (p $lt; 0.05), but no correlation between ptHcy and other plasma antioxidant vitamin levels in either gender. However, there were the negative correlations between ptHcy and plasma ${\alpha}$-carotene or ${\beta}$-carotene, and a positive correlation between ptHcy and lymphocyte DNA damage. A significantly low level of ${\alpha}$-carotene or ${\beta}$-carotene was found in male subjects with elevated ptHcy (${\geq}\;15\;{\mu}mol/L$), as compared to those with lower plasma homocysteine. These study results confirmed the views on the association between plasma homocysteine and oxidative stress markers in humans and support the hypothesis that homocysteine promotes the oxidative environment by counteracting the antioxidant defense mechanism.

• Journal of Veterinary Clinics
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• v.29 no.4
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• pp.277-282
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• 2012

This study was conducted to evaluate whether plasma homocysteine levels were related to obesity or its contributing factors (e.g., lipids, insulin, glucose, glucagon, and fructosamine) in dogs without systemic diseases such as diabetes or renal failure. For achieving our study goal, 100 client-owned dogs without systemic diseases were enrolled in this study. Fasting glucose concentration; lipid profile (i.e., total triglycerides [TG], total cholesterol [TC], highdensity lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol [LDL-C]); and fructosamine, insulin, and glucagon levels were determined. The dogs were subdivided by the body condition score (BCS). The median levels of homocysteine were considerably higher in obese dogs than in lean and normal dogs. Interestingly, not only was homocysteine positively associated with the level of HDL-C, but also found to have a significant positive association with TG, TC, plasma glucagon levels, and fructosamine. In contrast, LDL-C, fasting glucose and insulin did not show any association with homocysteine. The findings presented, suggest that elevated levels of homocysteine may play a biological role in obesity in dogs.

• Biomedical Science Letters
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• v.3 no.1
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• pp.29-35
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• 1997

Cardiovascular disease has been the leading cause of death among patients with chronic renal failure. Many reports have been described that homocysteine is one of the independent risk factor to the occulsive vascular disease. In this study, HPLC/FLD (high performance liquid chromatography-fluorescence detector) technique was used to measure homocysteine level in patients with chronic renal failure and normal control group. The detection limit and recovery of total plasma homocysteine using HPLC/FLD were 98.6$\pm$5.8% and 0.2 nmol/ml, respectively. The linearity of this method was established in concentration range of 2~50 nmol/ml (correlation coefficient=0.9997). The concentrations of total plasma homocysteine were 6.81$\pm$1.54 nmol/ml and 27.28$\pm$14.94 nmol/ml in normal control (n=20) and patient group (n=90), respectively (p<0.05). In this study, the HPLC/FLD method showed high sensitivity and reproducibility for a routine clinical laboratory testing. Moreover determination of homocysteine level in plasma might be useful for a biochemical marker for predicting the cardiovascular diseases and for monitoring of therapeutic effect of lowering homocysteine in patients with chronic renal failure.

• Journal of Nutrition and Health
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• v.34 no.4
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• pp.393-400
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• 2001

We examined the relationship between plasma folate and total homocysteine(Hcy) levels and the distribution of plasma folate and Hcy levels from 204 Korean adults(113 men and 91 women aged between 20yr and 69yr). Plasma folate levels were significantly lower in men(12.2nmol/L) than in women(14.6nmol/L) after controlling for smoking and drinking(p<0.05). Plasma Hcy levels were significantly higher in men(13.9$\mu$mol/L) than in women(11.8$\mu$mol/L) after controlling and drinking. Plasma Hcy levels were more more strongly correlated with plasma folate in women(${\gamma}$=-0.321, p<0.05) than in men(${\gamma}$=-0.202, p<0.05), but the difference between men and women was no longer statistically significant controlling for plasma folate concentration. Prevalence of mild homocysteinemia(plama Hcy>15$\mu$mol/L) was greatest among subjects with lowest folate status. These results indicate a strong association between plasma Hcy concentration and folate status and the poor folate status is the strong causative factor of mild homocysteinemia. (Korean J Nutrition 34(4) : 393~400, 2001)

• Asian-Australasian Journal of Animal Sciences
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• v.27 no.12
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• pp.1744-1748
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• 2014

A dose-response experiment with seven supplemental pyridoxine levels (0, 0.66, 1.32, 1.98, 2.64, 3.30, and 3.96 mg/kg) was conducted to investigate the effects of pyridoxine on growth performance and plasma aminotransferases and homocysteine of White Pekin ducks and to estimate pyridoxine requirement for these birds. A total of 336 one-day-old male White Pekin ducks were divided to 7 experimental treatments and each treatment contained 8 replicate pens with 6 birds per pen. Ducks were reared in raised wire-floor pens from hatch to 28 d of age. At 28 d of age, the weight gain, feed intake, feed/gain, and the aspartate aminotransferase, alanine aminotransferase, and homocysteine in plasma of ducks from each pen were all measured. In our study, the pyridoxine deficiency of ducks was characterized by growth depression, decreasing plasma aspartate aminotransferase activity and increasing plasma homocysteine. The ducks fed vitamin $B_6$-deficient basal diets had the worst weight gain and feed/gain among all birds and this growth depression was alleviated (p<0.05) when pyridoxine was supplemented to basal diets. On the other hand, plasma aspartate aminotransferase and homocysteine may be the sensitive indicators for vitamin $B_6$ status of ducks. The ducks fed basal diets had much lower aspartate aminotransferase activity and higher homocysteine level in plasma compared with other birds fed pyridoxine-supplemented diets (p<0.05). According to quadratic regression, the supplemental pyridoxine requirements of Pekin ducks from hatch to 28 days of age was 2.44 mg/kg for feed/gain and 2.08 mg/kg for plasma aspartate aminotransferase and the corresponding total requirements of this vitamin for these two criteria were 4.37 and 4.01 mg/kg when the pyridoxine concentration of basal diets was included, respectively. All data suggested that pyridoxine deficiency could cause growth retardation in ducks and the deficiency of this vitamin could be indicated by decreasing plasma aspartate aminotransferase activity and increasing plasma homocysteine.

• Korean Journal of Community Nutrition
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• v.6 no.3
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• pp.507-515
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• 2001

The elevation of plasma total homocysteine(tHcy) is now established as a risk factro for cardiovascular disease. It is also well known that plasma levels of folate and vitamin $B_{12}$ influences homocysteine metabolism as cofactors. Recently, the effects of health-related lifestyle factors, such as smoking, alcohol drinking coffee consumption, regular exercise, and etc, on plasma tHcy have been determined. The Hordalane Homocysteine Study revealed that smoking and coffee consumption are major deter minants of plasma tHcy as well as folate levels; however, the influence of alcohol intake is still controversial. In Koreans, the effects of lifestyle factors of plasma tHcy have not yet been determined. Thus, we investigated the relationships of various lifestyle determinants with plasma tHcy, folate, and vitamin $B_{12}$ levels and the erythrocyte folate concentrations in Korean adults (99 males and 96 fermales). Plasma tHcy levels were significantly hight in male subjects. On the contrary, plasma levels of folate and vitamin $B_{12}$ and erythrocyte folate concentration of the females were significantly higher than those of the males. Among the five lifestyle factors determined in the study, regular exercise significantly affects plasma tHcy levels only in the females, Contrary to the expectation, there were on significant differences in plasma tHcy levels between alcohol drinkers and non-alcohol drinkers as well as smokers and non-smokers. And also, plasma tHcy leverls were not different between coffee consumers and non-coffee consumer and between green tea consumers and non-green tea consumers. Although alcohol intake did not influence plasma tHcy levels, the duration, frequency, and amount of alcohol drinking showed significant negative relationships with plasma folate levers. These results indicate the regular exercise and alcohol intake might influence plasma levels of tHcy and folate in Koreans, although the results were not reveled in both sexes.

• Journal of Nutrition and Health
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• v.42 no.2
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• pp.107-118
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• 2009

In patients with type 2 diabetes, oxidative stress could be increased by their metabolic changes. Elevated plasma homocysteine is considered as one of markers of enhanced oxidative stress. Due to oxidative stress, some complications like cardiovascular or renal diseases may develop in type 2 diabetes patients. Plasma homocysteine concentration may be increased if folate status were inadequate. Protective effects against oxidative stress may be diminished if the status of anti-oxidative nutrient as vitamin C was poor. It is, therefore, important to maintain adequate status of folate and vitamin C in type 2 diabetes patients. Thus, this study was performed to determine the effects of supplementation of folate and/or ascorbate on blood glycated hemoglobin ($HbA_{1c}$) level, serum concentrations of homocysteine and cholesterol, plasma oxidized low density-lipoprotein (LDL), concentration and plasma glutathione peroxidase (GSH-Px) activity in the patients with type 2 diabetes. A total of 92 type 2 diabetes patients participated voluntarily with written consents. They were divided into one of the four experimental groups; Control (C), Folate-supplemented (F), Ascorbate-supplemented (A), and Folate plus ascorbate-supplemented (FA). The subjects in C were taken placebo, those in F were supplemented 1 mg of folate, those in A received 1,000 mg of ascorbate, and those in FA were given 1 mg of folate plus 1,000 mg of ascorbate daily for 4 weeks. Supplementation of folate or ascorbate resulted to increase serum folate level or plasma ascorbate concentration apparently, respectively. Folate supplementation not ascorbate seemed to decrease plasma concentrations of homocysteine and oxidized LDL and reduce plasma GSH-Px activity. There might not be synergic effect of the supplementation of folate plus ascorbate. The results indicate that oxidative stress in the patients with type 2 diabetes may lower mainly by folate supplementation.

• Nutritional Sciences
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• v.9 no.1
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• pp.35-41
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• 2006

It should be concerned to the women with mutated genotype of methylenetetrahydrofolate reductase (MTHFR), C677T or A1298C, since they need more folate than those with wild genotypes. In this study, we evaluated the folate status of Korean women of childbearing age according to their MTHFR polymorpiysm. Dietary folate intakes, plasma and erythrocyte folate concentrations, plasma homocysteine concentrations, and urinary excretions of para-aminobenzoylglutamate (pABG) and para-acetoamidobenzoylglutamate (ApABG) of twenty-five subjects aged between 19 and 35 years old were determined Folate intakes seemed to be inadequate, being only three-quarters of the Korean RDA of folate. More than one-quarter of the subjects was exposed to folate deficiency risk as determined by erythrocyte folate concentration and almost one-quarter of the subjects showed hyperhomocysteinemia, although they had normal plasma folate concentrations. Urinary excretions of pABG and ApABG seemed to be low and ApABG constituted more than $85\%$ of total folate catabolites. There were no significant differences in dietary folate intakes, plasma concentrations of folate and homocysteine, and urinary excretions of pABG and ApABG among the geneotypes of both C677T and A1298C. However, the subjects with 1298AC genotype had significantly lower erythrocyte folate concentration than those with 1298AA. Erythrocyte folate concentration showed an inverse relationship with plasma homocysteine concentration and positive relationships with urinary excretions of pABG and ApABG. The results of this study imply that mutations of 677C$\rightarrow$T and 1298A$\rightarrow$C in the study were not associated with decreased plasma folate and raised plasma homocysteine concentrations. A1298C polymorphism night be, however, more influential on erythrocyte folate concentration than C677T polymorphism, and urinary excretions of folate catabolites, pABG and ApABG, might be reliable indexes of folate nutritional status like plasma homocysteine concentrations.

• Clinical and Experimental Reproductive Medicine
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• v.31 no.3
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• pp.183-190
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• 2004

Objectives: Methylenetetrahydrofolate reductase (MTHFR) mutation are commonly associated with hyperhomocysteinemia, and through their defects in homocysteine metabolism, they have been implicated as a risk factor for recurrent spontaneous abortion. Recent report describe that 28-bp tandem repeat polymorphism in thymidylate synthase enhancer region (TSER) that influence enzyme activity would affect plasma homocysteine level. We have investigated the relationship between TSER genotype and plasma homocysteine level in 54 patients with recurrent spontaneous abortion. Methods: Plasma homocysteine level was measured by fluorescent polarizing immunoassay. MTHFR mutation (C677T and A1298C) was identified by PCR-restriction fragment length polymorphism assay and TSER mutation was analyzed by PCR method. The data were analyzed using the program SAS 8.2 for Windows. Results: Total homocysteine level was significantly higher in MTHFR 677TT genotype ($9.80{\pm}3.87{\mu}mol/L$) than MTHFR 677CC genotype ($8.14{\pm}1.74{\mu}mol/L$) in Korean patients with unexplained recurrent spontaneous abortion (p=0.0143). However, the plasma homocysteine level was not significantly different in the MTHFR 1298AA ($8.42{\pm}2.65{\mu}mol/L$) and 1298CC ($6.09{\pm}0.32{\mu}mol/L$; p=0.2058) and, TSER 2R2R ($8.61{\pm}1.68{\mu}mol/L$) and 3R3R ($8.05{\pm}2.81{\mu}mol/L$; p=0.9319) mutant genotypes, respectively. In this study, we found the combination effects of TSER and MTHFR C677T genotypes. Plasma homocysteine levels were the highest ($11.47{\pm}4.66{\mu}mol/L$) in individuals with TSER 3R3R ($8.05{\pm}2.81{\mu}mol/L$) and MTHFR 677TT ($9.80{\pm}3.87{\mu}mol/L$) genotypes. Individuals with a combination of both TSER 2R2R/2R3R and MTHFR 677CC/CT genotypes ($7.69{\pm}1.77{\mu}mol/L$) had lower plasma homocysteine levels than TSER 2R2R ($8.61{\pm}1.68{\mu}mol/L$) and MTHR 677CC ($8.14{\pm}1.74{\mu}mol/L$) genotypes, respectively. The effect of MTHFR polymorphism in the homocysteine metabolism appears to be stronger than that of TSER polymorphism. Conclusion: Although statistically not significant, we found the elevated level of plasma homocysteine in combined genotypes with TSER and MTHFR (C677T and A1298C) in Korean patients with unexplained habitual abortion. In this study, we reported the possibility that TSER polymorphism is a genetic determinant of plasma homocysteine levels in the Korean patients as well as MTHFR C677T polymorphism. A large prospective study is needed to verify our findings.

• Korean Journal of Clinical Laboratory Science
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• v.37 no.1
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• pp.22-26
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• 2005

Total homocysteine is now considered a risk factor for cardiovascular diseases. I increased interest has led to a multitude of studies requiring the determination of total homocysteine in conjunction with other factor. There are various methods for measuring total homocysteine, including HPLC, FPIA, GC-MS and LC-MS/MS. The most recent method for measuring total homocysteine uses a deuterium-labelled internal standard and tandem mass spectrometry. This development requires no derivatization and therefore leads to an increase in sample throughput compared to other techniques. We have evaluated the method for homocysteine by the LC-MS/MS method, and the correlation between the FPIA method and the LC-MS/MS method. The standard curve (0, 5, 10, 20, 50, 100 uM) was linear over the range examined (up to 100 uM). The lower limit of quantification (CV < 10 %) was 0.5 uM/L and the lower limit of detection (S/N >3) was 0.1 uM/L. Intra-assay variation and inter-assay variation were both <6 %. The comparision study for homocysteine concentration showed good correlation (r=0.9684) between the FPIA method and LC-MS/MS methods. Our conclusion is that the method showed relatively good precision, and was rapid and accurate.