• The Journal of Internal Korean Medicine
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• v.23 no.1
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• pp.1-4
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• 2002

Objective : Hyperhomocysteinemia has been proven to be an independent risk factor for stroke. The genetic mutation of methylenetetrahydrofolate reductase(MTHFR) elevates serum homocysteine level, but it still remains controversial whether the MTHFR gene mutation could be a predictor of ischemic stroke. Therefore, we studied if this genetic defect could cause ischemic stroke independently. Methods : We gathered ischemic stroke subjects and age, sex-matched controls. Age, gender, past medical history, smoking habit, serum homocysteine level, and the MTHFR genotype were recorded. General characteristics of ischemic stroke subjects were compared to the controls. We classified the stroke according to the related vessels(small and large artery infarction) and single lesion and multiple infraction. Relevant risk of the MTHFR genotype was evaluated in each stroke subtype with multiple logistic regression analysis. Results : When the controls were compared to the whole ischemic stroke, there was no specific difference except some medical histories. However, further analysis based on stroke subtypes showed important results. The small artery infarction group, multiple infraction group had significant odds ratio of the MTHFR TT genotype adjusted for age, gender, medical history and smoking habit. Conclusions : The MTHFR TT genotype is an independent risk factor for certain types of ischemic stroke, small artery infarction and multiple infarction.

• Tuberculosis and Respiratory Diseases
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• v.64 no.6
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• pp.460-465
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• 2008

Incidences of pulmonary thromboembolism markedly increase with age. Risk factors of pulmonary thromboembolism are surgery, trauma, acute medical illness, immobilization, pregnancy, usage of hormone, and advanced age. In the cases of thrombomembolism occurred in young age, the possibility of thrombophilc state is needed to be investigated. Among many diseases or state associated thrombophilic state, homocyteinemia should be considered a cause of thromboembolism before fifth decade. Homocyteinemia is caused by deficiency of N-5-methyltetrahydrofolate, cystathionie ${\beta}$-synthase and vitamin B12. The presence of the mutation of 5,10-methyleneterahydrofolate lead to homocyteinemia by deficiency of N-5-methyltetrahydrofolate. Homocysteine is acknowledged the risk factor of cardiovascular event, and storke. Homocysteinemia can be the cause of thromboemboism via damaging endotheial cell. We present two cases of pulmonary thromboembolism in young age which seem to be associated with homocysteinemia precipitated by mutation of 5,10-methyleneterahydrofolate.

• Journal of Preventive Medicine and Public Health
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• v.45 no.6
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• pp.387-393
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• 2012

Objectives: Even though several epidemiological studies have observed positive associations between blood lead levels and homocysteine, no study has examined whether this association differs by the levels of micronutrients, such as folate, vitamin B6, and vitamin B12, which are involved in the metabolism of homocysteine. In this study, we examined the interactions between micronutrients and blood lead on homocysteine levels. Methods: This study was performed with 4089 adults aged ${\geq}20$ years old in the US general population using the National Health and Nutrition Examination Survey 2003-2004. Results: There were significant or marginally significant interactions between micronutrients and blood lead levels on mean homocysteine levels. Positive associations between blood lead and homocysteine were clearly observed among subjects with low levels of folate or low vitamin B6 (p-trend <0.01, respectively). However, in the case of vitamin B12, there was a stronger positive association between blood lead and homocysteine among subjects with high levels of vitamin B12, compared to those with low levels of vitamin B12. In fact, the levels of homocysteine were already high among subjects low in vitamin B12, irrespective of blood lead levels. When we used hyperhomocysteinemia (homocysteine>15 ${\mu}mol/L$) as the outcome, there were similar patterns of interaction, though p-values for each interaction failed to reach statistical significance. Conclusions: In the current study, the association between blood lead and homocysteine differed based on the levels of folate, vitamin B6, or vitamin B12 present in the blood. It may be important to keep sufficient levels of these micronutrients to prevent the possible harmful effects of lead exposure on homocysteine levels.

• Journal of Nutrition and Health
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• v.31 no.7
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• pp.1121-1129
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• 1998

The critical role of folate vitamin in the remethylation pathway for methionine synthesis from homocysteine has been well documented. Hyperhomocysteinemia resulting from inadequate folate nutrition has been implicated in increased incidence of macrovascular diseases, colorectal cancer, neural tube defects, etc. Chronic exposure to ethanol impairs folate nutrition and one-carbon metabolism in the liver, which often results in fatty liver due to a defective remethylation process. This study was carried out to investigate the chronic effects of moderate levels of alcohol and dietary 131ate on plasma homocysteine levels, and on histopathology and biochemical functions of the liver Rats were raised on experimental diets with three levels of folate(0, 2, 8mg/kg diet), and 50% ethanol(1.8m1/kg body weight) was administered intragastrically by intubation tubes three times a week for 10 weeks. Plasma homocysteine concentrations were found to be significantly influenced by dietary folate intake and alcohol administration. Among all treatment groups, Plasma homocysteine levels were highest in the animals receiving a combined treatment of folate deficient diet and alcohol administration. Plasma homocysteine concentration was negatively correlated with folate concentration in the plasma(p<0.01) and liver(p<0.05). Among alcohol treated rats, increase in plasma homocysteine values due to ethanol was prevented by 131ate supplementation. When liver histological tests were performed, macrovascular and microvascular fatty changes and spotted necrosis were observed more frequently in folate-deficient animals diet than those on folate-adequate and folate-supplemented diets in alcohol-treated rats. These results indicate that folate supplementation above the recommended level might be beneficial in the prevention of alcohol-related hyperhomocystei-nemia and abnormal histologic changes in the liver due. (Korean J Nutrition 31(7) : l121-l129, 1998)

• Journal of Nutrition and Health
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• v.38 no.7
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• pp.495-502
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• 2005

This study was performed to investigate effects of dietary folic acid supplementation on plasma homocysteine levels, thiobarbituric acid reactive substance s (TBARS) level s and liver SAM/SAH ratio in hyperhomocysteinaemia-induced pregnant rats. Forty-two female Sprague-Dawley rats were divided three groups (C: control diet, HFD: $0.3\%$ homocystine and 0 mg folic acid diet, HFS: $0.3\%$ homocystine and 8 mg/kg folic acid diet) according to homocystine and folic acid levels in the diet. They were fed experimental diets for 5 weeks prior to the mating and also during the entire period of pregnancy till gestational day 20. Dietary folic acid supplementation caused a significant decrease in plasma homocysteine levels which had been increased by a homocystine-diet, with a concomitant increase in plasma and liver folate levels. Liver TBARS levels in homocysteine-folic acid-deficient group (HFD) were higher than those in control group. Dietary folic acid supplementation increased hepatic SAM/SAM ratio in homocysteine-folic acid- sopplemetantion group (HFS) when compared to the HFD (p < 0.05). These data suggest that folate depletion and elevated plasma homocysteine may promote oxidative stress in rat livers and influence the remethylation cycle of the homocysteine metabolism detrimentally. In conclusion, dietary folic acid supplementation was found to be effective for lowering plasma homocysteine levels, relieving oxidative stress, and improving the methylation status in the body.

• 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.

• Journal of Dairy Science and Biotechnology
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• v.32 no.1
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• pp.17-29
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• 2014

GRAS probiotics can be used to modulate intestinal microbiota and to alleviate various gastrointestinal disorders. In several recent studies, researchers have explored the potential expansion and usability of probiotics to reduce the risk factors associated with diseases, including obesity, hypercholesterolemia, arterial hypertension, hyperhomocysteinemia, and oxidative stress. In this review, our aim was to clarify the mechanism underlying interactions between hosts (animal or human) and probiotics and the beneficial effects of probiotics on human health.

• Journal of Nutrition and Health
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• v.44 no.6
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• pp.498-506
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• 2011

This study examined the relationship among plasma homocysteine, folate, and vitamin $B_{12}$ levels and neurocognitive function in 118 community-dwelling elderly subjects (mean age, $75.1{\pm}6.7$ years). The Mini-Mental State Examination (MMSE-KC) was used to screen and assess neurocognitive function in the participants. Dietary intake data including the use of dietary supplements were obtained using the 24-hour recall method by well-trained interviewers. Plasma folate and vitamin $B_{12}$ concentrations were analyzed by radioimmunoassay, and homocysteine was assessed by a high performance liquid chromatography-fluorescence method. The proportions of participants with suboptimal levels of plasma folate (< 3 ng/mL), vitamin $B_{12}$ (< 221 pmol/mL), and homocysteine (> $15{\mu}mol/L$) were 16.1%, 5.9%, and 21.2%, respectively. A multiple regression analysis showed that plasma homocysteine was negatively associated with plasma folate and vitamin $B_{12}$ levels. The MMSE-KC test scores were significantly associated with plasma homocysteine and folate, but not with vitamin $B_{12}$, after adjusting for age, gender, body mass index, living with spouse, education, current smoking, energy intake, and chronic diseases such as hypertension, diabetes, thyroid disease, dyslipidemia, stroke, and cardiovascular disease. A general linear model adjusted for covariates revealed that MMSE-KC test scores increased from the lowest to the highest quartiles of vitamin $B_1$, vitamin $B_2$, vitamin $B_6$, vitamin $B_{12}$, and vitamin C intake (p for trend = 0.012, 0.039, 0.014, 0.046, 0.026, respectively). These results indicate that the problem of folate inadequacy and hyperhomocysteinemia are highly prevalent among community-dwelling elderly people and that dietary intake of the B vitamins and vitamin C is positively associated with cognitive function scores.

• Clinical and Experimental Reproductive Medicine
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• v.29 no.3
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• pp.215-222
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• 2002

Objective : Previous studies have suggested that hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR C677T) mutations are associated with increased risk of recurrent spontaneous abortion (RSA). Recently, a second site polymorphism in MTHFR, 1298A-->C, which changes a glutamic acid into an alanine residue, was shown to be associated with a decreased enzyme activity. We tested whether the variant alleles of MTHFR C677T and A1298C are risk factor (biomarker) for RSA. Materials and Methods: We analyzed DNA from a case-control study in the Korean DNA was extracted from blood samples of 118 patients with RSA and 123 healthy fertile patients as the controls. MTHFR variant alleles were determined by a PCR-restriction fragment length polymorphism assay. Results: We found no evidence for an association between 677TT genotype and risk of RSA (OR=1.95, 95% CI=$0.84{\sim}4.50$, p=0.12). However, the MTHFR 1298AC (OR=0.36, 95% CI=$0.20{\sim}0.63$, p=0.0004) and 1298AC+CC (OR=0.35, 95% CI=$0.20{\sim}0.61$, p=0.0002) genotypes were lower among 118 RSA cases compared with 123 controls, conferring a 2.8-fold decrease in risk of RSA, respectively. Moreover, the combined genotypes of MTHFR 677CC/1298AC (OR=0.30, 95% CI=$0.10{\sim}0.88$, p=0.029) and 677CT/1298AC (OR=0.77, 95% CI=$0.60{\sim}0.99$, p=0.043) also showed significantly lower risk than those with MTHFR 677CC/1298AA type. Conclusion: MTHFR 1298AC, MTHFR 677CC/1298AC and 677CT/1298AC genotypes may represent genetic markers for the protection of RSA at least in Korean women.

• Clinical and Experimental Reproductive Medicine
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• v.38 no.3
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• pp.168-173
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• 2011

Objective: To examine the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and hyperhomocysteinemia in women with unexplained recurrent miscarriages (RM) and to investigate the association between MTHFR genotype variants and alloimmune activation, proportion of peripheral blood natural killer (pbNK) cells. Methods: A total of 39 patients with a history of two or more unexplained miscarriages were recruited to this study. The controls were women who had a live birth without a history of RM (n=50). The proportion of pbNK cells was measured by flow cytometry. Plasma homocysteine levels and the incidence of the MTHFR variant of the RM and control groups were compared. The proportion of pbNK cells was compared to the MTHFR variants in the RM group. Results: No differences were found between the two groups' mean plasma homocysteine levels ($7.6{\pm}1.5{\mu}mol$/L vs. $7.1{\pm}2.1{\mu}mol$/L) or incidence of the MTHFR genotype variant (CC, 35% vs. 33%; CT, 40% vs. 53%; and TT, 25% vs. 14%). In the RM group, individuals with the TT variant ($7.7{\pm}1.1{\mu}mol$/L) had higher homocysteine levels than those with the CC and CT variants ($7.4{\pm}1.9{\mu}mol$/L and $7.4{\pm}1.2{\mu}mol$/L) and those with the CT variant ($19.2{\pm}8.1%$) had a higher proportion of CD3-/CD56+ pbNK cells than those with the CC and TT variants ($17.7{\pm}6.6%$ and $17.9{\pm}7.0%$), but the results of both comparisons were statistically insignificant. Conclusion: These preliminary results show no difference in plasma homocysteine levels between the RM and control groups or among MTHFR genotype variants in the RM group, which may suggest that the plasma homocysteine level is difficult to use as a predictive marker of RM in the Korean population. A study of a larger number of patients is needed.