Mean Plasma Homocysteine Levels Research Articles

Association of high blood pressure with raised homocysteine level among urban population- A case control study

Abstract Introduction: Hypertension is a major risk factor for cardiovascular diseases. Raised homocysteine level is also an important independent risk factor for CVD. This study sought to determine whether there is any relationship between plasma homocysteine and blood pressure levels. Method: A case control study was conducted among 200 hypertensive cases and 200 normal healthy control groups. Cases were from the Department of medicine and hypertensive clinics at GMC, Baramati and similar controls were selected from patients’ neighborhood. Detailed clinical assessment as well as plasma homocysteine level were assessed and compared in both. Results: Hypertensive cases had higher mean homocysteine level (21.3 ± 4.6 μmol/L) from controls (13.0 ± 6.0 μmol/L), p<0.001. Homocysteine is positively correlated with both systolic and diastolic blood pressure among both hypertensive patients and healthy controls. In both hypertensive subjects and healthy control, homocysteine level has weak positive correlation with DBP and moderate to strong positive correlation with SBP. The hypertensive cases had very high chance (OR=52.4) of developing hyperhomocysteinemia (>15 μmol/L), p<0.001. Conclusion: This study showed higher mean plasma homocysteine levels in hypertensive subjects than controls. Serum homocysteine concentrations were positively associated with both systolic and diastolic blood pressure levels in a general adult population.

Relationship between MTHFR C677T, homocysteine, and ischemic stroke in a large sample of the Han Chinese population.

Ischemic stroke, one of the prevalent causes of death and disability worldwide, is linked to environmental and genetic factors, including polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene involved in homocysteine metabolism. The present study aimed to explore the relationship between the MTHFR C677T variant, plasma homocysteine, and risk of developing large-artery atherosclerotic ischemic stroke (LAAIS) among Han Chinese.A population-based case-control study, which included 1810 patients with LAAIS and 1765 unrelated control subjects, was conducted. Compared to the controls, LAAIS patients had a significantly higher prevalence of hypertension, diabetes mellitus, smoking, and alcohol consumption (P < .001), as well as significantly higher mean fasting blood glucose, triglyceride, total cholesterol, and plasma homocysteine levels (P < .001). The TT homozygous genotype correlated with increased risk of developing LAAIS, as indicated by a significantly higher odds ratio (OR) compared to the CT and CC genotypes, in both additive (OR = 3.215, P = .01) and recessive models (OR = 3.265, P = .01). The plasma homocysteine level was genotype-dependent according to the following trend: TT > CT > CC.In conclusion, our data demonstrate that, in spite of its low prevalence in both patients and controls (1.5% vs 0.8%), the MTHFR C677T variant could, at least in part, affect homocysteine levels and this, either alone or in combination with other factors, increases the risk of LAAIS.

Plasma homocysteine and macular thickness in older adults-the Rugao Longevity and Aging Study.

To determine the association of plasma homocysteine levels with retinal layer thickness in a large community cohort of older adults. The Rugao Longevity and Ageing Study is an observational, prospective and community-based cohort study. A total of 989 older adults who underwent spectral-domain optical coherence tomography (SD-OCT) were included and analyzed. Foveal, macular retinal nerve fibre layer (mRNFL) and ganglion cell layer plus inner plexiform layer (GC-IPL) thicknesses were measured by SD-OCT. Plasma homocysteine levels were measured using chemiluminescence immunoassay. Linear regression analyses were performed to evaluate the relationship between plasma homocysteine and retinal layer thickness while controlling for confounding factors. Of the 989 participants, 500 (50.56%) were men. The mean age was 78.26 (4.58) years, and the mean plasma homocysteine level was 16.38 (8.05) μmol/L. In multivariable analyses, each unit increase in plasma homocysteine was associated with an 8.84 × 10-2 (95% CI: -16.54 × 10-2 to -1.15 × 10-2, p = 0.032) μm decrease in the average inner thickness of the GC-IPL after controlling for confounding factors. The association remained significant even in participants without major cardiovascular disease or diabetes (β = -10.33 × 10-2, 95% CI: -18.49 × 10-2 to -2.18 × 10-2, p = 0.013). No significant associations of plasma homocysteine levels with macular thickness or mRNFL were found in primary and sensitivity analyses (p > 0.05). Increased plasma homocysteine levels are associated with a thinner GC-IPL. Plasma homocysteine may be a risk factor for thinner retinas in older adults.

Relationship between plasma homocysteine and blood pressure in hypertensive Northern-Nigerians.

The study sought to determine whether there is any relationship between plasma homocysteine and blood pressure levels in Nigerians with essential hypertension. It was a cross-sectional analytical study done on 120 randomly selected hypertensive patients and 120 normal healthy controls seen at the large Conference hall of the Ahmadu Bello University (ABU) Medical Centre, Zaria as well as the ABU Teaching Hospital, Zaria, Northern-Nigeria. Pearson's Correlation and Binary Logistic Regression analysis determined the relationship between homocysteine and hypertension. Hyperhomocysteinaemia found in the hypertensive patients (22.8 ± 6.6 µmol/L) differed significantly (p<0.001) from controls (10.9 ± 2.8 µmol/L) with significant (p<0.001), blood pressure difference between both groups. Homocysteine significantly positively correlated with systolic (r = 0.51, p<0.001) and diastolic (r = 0.47, p<0.001) blood pressures in hypertensive subjects. The relation of plasma hcy to hypertension was statistically significant for SBP; OR: 1.08 (95% CI, 1.05-1.11) and DBP; OR: 1.08 (95% CI, 1.03-1.13) in the unadjusted model. When adjusted for confounding variables, hcy was significantly related to SBP; OR: 1.1 (95% CI, 1.04-1.18) but not DBP (p=0.25; OR: 1.06 (95 % CI, 0.96-1.18). The mean plasma folate level was high (115.2 ± 48.0 ng/mL) in the hypertensive subjects. The hyperhomocysteinaemic subjects showed a 2.8 times Odds of developing hypertension. This study showed higher mean plasma homocysteine levels in hypertensives than controls not accounted for by sub-optimal folate levels. Hyperhomocysteinaemia showed a positive relationship to systolic hypertension after adjusting for confounders.

Homocysteine Levels in Patients with Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome in Ibadan

Introduction: Homocysteine is produced from the conversion of methionine to cysteine. Conditions resulting in hyper homocysteinemia leads to an increased risk of both arterial and venous thromboembolisms by about 2 fold. 20% of HIV infected patients with objective evidence of venous thromboembolism are found to be thrombophilic with higher homocysteine levels. We enquired into homocysteine levels prior to the development of a clinical evidence of a venous thrombus in both HAART naïve and those on HAART of HIV /AIDS population. We evaluated the association between homocysteine, CD4 lymphocyte count and ART use in order to identify possible risk factors for hyper homocysteinemia in HIV population.&#x0D; Method: Employing a cross sectional design; we compared mean plasma levels of homocysteine, full blood count parameters and CD4+ lymphocytes counts in HIV positive patients and HIV negative controls. One hundred and twenty patients with HIV infection attending the APIN clinic at the University College Hospital Ibadan and St Mary’s Catholic Hospital Eleta Ibadan and one hundred and twenty-six HIV negative healthy controls were compared in the study.&#x0D; Results: Fifty-nine point one percent of the HIV positive patient had hyperhomocysteinemia i.e. homocysteine levels of &gt;18µmol/l. The mean plasma homocysteine levels were significantly higher at 24.4µmol/l (SD=13.8) (CI -2 to -8; p=0.002) in the HIV positive group compared with 19.5µmol/L (SD=10.6) in the control group. The use of Anti-retroviral drugs was not associated with higher homocysteine level in the seropositive group and neither were factors like age, gender or the use of combined oral contraceptive pills. There was no correlation between CD4 cell count and homocysteine levels (r= -0.01; p=0.9).&#x0D; Conclusion: Homocysteine levels are elevated in HIV positive patients and hyperhomocysteinemia was found in a significant number of HIV positive patients. None of the patients investigated had features of thromboembolism or outright deep venous thrombosis. Neither CD4 cell counts nor traditional risk factors were associated with the higher homocysteine levels.

Hyperhomocysteinemia and folate levels in normal healthy Nigerians living in Zaria: Subanalysis of ABU homocysteine cross-sectional survey.

Background:This study aimed to determine the prevalence of hyperhomocysteinemia and folate status in a sample of normal healthy Nigerians living in Zaria as well as assess the relationship between homocysteine, folate, and blood pressure (BP) levels.Methods:It was a cross-sectional analytical study carried out among 65 normal healthy volunteers aged 18–65 years. Participants were randomly selected from willing patient escorts, hospital employees, and willing staff presenting at the Ahmadu Bello University Medical Centre, Zaria and Ahmadu Bello University Teaching Hospital, Zaria, Nigeria. The percentage of participants who had high homocysteine levels as well as their plasma folate status was determined.Results:There were 9.2% with hyperhomocysteinemia >15 μmol/L and 51% with hyperhomocysteinemia >10 μmol/L. The mean plasma homocysteine level was 10.8 ± 2.7 μmol/L with male and female values of 10.7 ± 2.6 and 10.8 ± 2.8, respectively (P = 0.87). The mean plasma folate level was high (116.7 ± 44.0 ng/mL) with male value of (111.5 ± 44.9 ng/mL) which did not differ significantly (P = 0.37) from that of females (121.4 ± 43.3 ng/mL). Homocysteine showed a positive significant (P = 0.01) relationship with folate but not with BP's (P > 0.05).Conclusion:There is a high prevalence of hyperhomocysteinemia in normal healthy Northern-Nigerians which cannot be accounted for by suboptimal folate levels. Hyperhomocysteinemia may not be a risk factor for cardiovascular disease in normal healthy Nigerians despite its high levels as it showed no significant relationship with BP.Context:L’ étude vise à determiner la prévalence de l’hyper-homocystéinémie de l’état du folate en prenant comme echantillon dans le cas du nigérian en bonne santé vivant à Zaria, ainsi que l’évaluation de la relation qui existe entre l’homocystéine, le folate par rapport au niveau de croissance de la pression artérielle.

Impact of Dyrk1A level on alcohol metabolism

Alcoholic liver diseases arise from complex phenotypes involving many genetic factors. It is quite common to find hyperhomocysteinemia in chronic alcoholic liver diseases, mainly due to deregulation of hepatic homocysteine metabolism. Dyrk1A, involved in homocysteine metabolism at different crossroads, is decreased in liver of hyperhomocysteinemic mice. Here, we hypothesized that Dyrk1A contributes to alcohol-induced hepatic impairment in mice. Control, hyperhomocysteinemic and mice overexpressing Dyrk1A were fed using a Lieber-DeCarli liquid diet with or without ethanol (5% v/v ethanol) for one month, and liver histological examination and liver biochemical function tests were performed. Plasma alanine aminotransferase and homocysteine levels were significantly decreased in mice overexpressing Dyrk1A compared to control mice with or without alcohol administration. On the contrary, the mean plasma alanine aminotransferase and homocysteine levels were significantly higher in hyperhomocysteinemic mice than that of control mice after alcohol administration. Paraoxonase 1 and CYP2E1, two phase I xenobiotic metabolizing enzymes, were found increased in the three groups of mice after alcohol administration. However, NQO1, a phase II enzyme, was only found increased in hyperhomocysteinemic mice after alcohol exposure, suggesting a greater effect of alcohol in liver of hyperhomocysteinemic mice. We observed positive correlations between hepatic alcohol dehydrogenase activity, Dyrk1A and ADH4 protein levels. Importantly, a deleterious effect of alcohol consumption on hepatic Dyrk1A protein level was found. Our study reveals on the one hand a role of Dyrk1A in ethanol metabolism and on the other hand a deleterious effect of alcohol administration on hepatic Dyrk1A level.

The relationship between plasma homocysteine level and HLA‐B51 in patients with Behcet's disease: a case‐control study

Various coagulation disorders have been reported to explain hypercoagulability state in Behcet's disease (BD). A possible negative association between human leukocyte antigen (HLA)-B51 and increased homocysteine level has been suggested in a previous report from Iranian patients with BD. The aim of this study was to find any possible relationship between plasma homocysteine levels and HLA-B51. In a case-control study, BD patients (fulfilling the new International Criteria for BD) and controls (who had similar clinical symptoms but BD was clinically excluded in them) were included. Mean plasma homocysteine levels measured by enzyme-linked immunosorbent assay in HLA-B51 positive and negative individuals both in patients and controls were compared by t-test, Mann-Whitney test and analysis of variance (F-test). Ninety-six BD patients and 152 controls were recruited. There was no significant difference between HLA-B51 positive and negative individuals either in the mean plasma homocysteine levels (13.59 ± 9.03 vs. 12.95 ± 4.98 μmol/L, P = 0.514), or in the prevalence of hyperhomocysteinemia (17% vs. 21.4%, P = 0.504). This was true both for BD and control groups. In HLA-B51 positive and negative BD patients, mean plasma homocysteine levels were 14.29 ± 12.02 and 12.62 ± 4.79 μmol/L, respectively (P = 0.33), and the prevalence of hyperhomocysteinemia was 20.8% versus 19.5% (P = 0.55). In the control group, the mean plasma homocysteine levels in HLA-B51 positive and negative individuals were 12.85 ± 4.28 and 13.14 ± 5.10 μmol/L, respectively (P = 0.794), and the prevalence of hyperhomocysteinemia was 13% versus 22.1% (P = 0.23). The difference was non-significant regarding sex (P > 0.71) and disease activity (P > 0.31). In contrast to our previous report, we found no relationship between plasma homocysteine levels and HLA-B51 in this study, either in BD or in the control group.

Association of methylenetetrahydrofolate reductase C677T and A1298C polymorphisms with myocardial infarction in Tunisian young patients

Myocardial infarction (MI) is an important clinical problem because of its large contribution to mortality. The objective of this study is to assess whether two methylenetetrahydrofolate reductase (MTHFR) polymorphisms, C677T and A1298C, were associated with MI among Tunisian patients. One hundred young patients (<47 years old) with MI were recruited and compared with 200 control subjects with no history of MI. The most common MI risk factors were investigated. Fasting plasma homocysteine levels were measured. Genotypes of the MTHFR C677T and A1298 polymorphisms were studied by polymerase chain reaction. The mean plasma homocysteine level in the study group was raised when compared with the control group. Homozygous MTHFR C677T mutation was observed in 2 (2 %) patients and in 17 (8.5 %) control subjects, whereas heterozygous MTHFR C677T mutation was detected in 82 (82 %) patients versus only 79 (39.5 %) in control subjects. The mean total homocysteine concentrations were significantly higher in individuals with the 677TT and CT genotypes. Our results indicate that C677T and A1298C MTHFR mutations and hyperhomocysteinemia contributed to the risk factors for MI.

Plasma Homocysteine Levels in Dry Eye Patients

To compare plasma homocysteine levels between patients with dry eye disease and normal control subjects. Plasma homocysteine (enzyme immunoassay), vitamin B12, and folate levels were determined in 38 patients with dry eye and in 38 controls. Characteristics of the dry eye and control groups were similar. The mean plasma homocysteine level was 16.38 ± 6.98 μmol/L in the dry eye group and 14.39 ± 5.11 μmol/L in the control group (P = 0.10, t test). Hyperhomocysteinemia was present in the 43.9% of the dry eye patients and 33.3% of the controls (P = 0.43, χ test). There were no statistical differences between dry eye and control groups regarding plasma vitamin B12 and folate levels (P = 0.72 and P = 0.69, respectively, t test). Plasma homocysteine levels in dry eye patients may be inadequate to give homocysteine a role in pathogenesis. However, in ocular diseases like glaucoma, plasma homocysteine levels are significantly higher, and associated dry eye disease may cause an additional increase in plasma homocysteine levels.

Correlation between elevated homocysteine levels and insulin resistance in infertile women with or without polycystic ovary syndrome in North Indian population

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting about 5 to 10% women of reproductive age group worldwide. This study was designed to examine the relationship between elevated homocysteine levels and insulin resistance (IR) in infertile women with or without PCOS. This cross sectional case control study was conducted in Department of Obstetrics and Gynaecology, Pathology and Medicine, CSM Medical University (Erstwhile KGMU), Lucknow, UP India. After informed consent, a total 90 infertile women were enrolled which included 50 diagnosed cases of PCOS according to Rotterdam consensus meeting 2003 and 40 healthy non PCOS as controls. Mean plasma homocysteine levels were significantly higher in PCOS women (11.8796±5.5) as compared to non PCOS women (7.8095±2.2). Obesity was found in 64% PCOS women and 37.5% of non PCOS women which was significant. Serum testosterone levels were elevated in 42% of PCOS women, but none of the women of non PCOS group had elevated testosterone levels. Amongst the PCOS patients (32/50), 64% were IR and (18/50) 36% were non insulin resistance (NIR) PCOS group which was stratified by HOMA-IR. Thirty-two women had mean HOMA-IR (5.95±1.27) designated PCOS IR and 18 had mean HOMA-IR (1.86±0.028) designated PCOS NIR. Elevated body mass index (BMI) was not significantly associated with IR in PCOS patients. BMI in PCOS IR was 27.43±3.096 and BMI in PCOS NIR was 25.728±2.609 (P<0.07). Homocysteine levels were significantly elevated in PCOS patients (mean 11.87±5.5) (All PCOS), IR PCOS (13.82±5.69 pmol/q) versus controls (7.80±2.29 pmol/L) (P<0.001). In conclusion, obesity is not an independent risk factor to increase plasma homocysteine levels in PCOS women. Key words: Homocysteine, polycystic ovary syndrome, insulin resistance, infertility.

Folic acid and vitamin B6 deficiencies related hyperhomocysteinemia in apparently healthy Pakistani adults; is mass micronutrient supplementation indicated in this population?

To determine the plasma/serum levels of homocysteine, and vitamins folate, B6 and B12, in Pakistani healthy adults. Cross-sectional study. The Aga Khan University, from October 2006 to April 2008. Fasting levels of plasma/serum folic acid, pyridoxal phosphate (PLP), vitamin B12 and homocysteine were determined in 290 apparently healthy hospital personnel from institutions in two cities of Pakistan. Spearman correlation test and linear regression analysis was conducted. There were 219 males and 71 females with mean age of 46+/-10.5 years and mean body mass index of 23.5 +/-3.8. Mean plasma homocysteine levels in Pakistani normal adults were found to be 17.95+/-8.4 micromol/l. Mean concentrations of plasma/serum folate, vitamin B12 and PLP were found to be 5+/-3.9 ng/ml, 522+/-296 pg/ml and 21.6+/-14 nmol/l, respectively. Serum/plasma levels of folate, vitamin B12 and PLP were negatively correlated with plasma homocysteine (rho coefficient=-0.367, p<0.001; -0.173, p=0.004; -0.185, p=0.002, respectively). Serum folate and plasma PLP levels were inversely related with plasma homocysteine, adjusted for gender, age, smoking and body mass index (p<0.001 and p=0.003, respectively). Percent deficiency values of folate, vitamin B6 and vitamin B12 were 39.7%, 52.8% and 6.6% respectively. The high levels of plasma homocysteine could indicate a reason for mass micronutrient supplementation to prevent the high incidence of cardiovascular disease observed in Pakistani population.

Hyperhomocysteinemia as a Risk Factor for IUGR

To study the role of hyperhomocysteinemia in patients with intrauterine growth retardation. 76 patients with intrauterine growth retardation were studied and compared with 50 controls which included pregnant patients without any pregnancy complications. Fasting Plasma homocysteine levels were measured and statistical analysis using tests of significance and logistic regression analysis was performed. Those in the study group were given homocysteine lowering agents for 6 wks and pregnancy outcome was studied. 57.8% women in the study group were found to have hyperhomocysteinemia. Logistic Regression analysis shows an OR of 2.45 in favor of occurrence of IUGR if homocysteine levels are raised which is statistically significant. Mean plasma homocysteine levels decreased after treatment for 6 wks but this decrease in the case of placebo group is marginal whereas the decrease in the homocysteine levels the treatment group. This implies that treatment has a definitive role in lowering of plasma homocysteine levels. The present study shows that hyperhomocysteinemia is associated with IUGR and should be identified as a risk factor as correction favors pregnancy outcome.

Application of LC-MS/MS analysis of plasma amino acids profiles in children with autism

Autism is a neurodevelopmental disability that is usually diagnosed before age 3 years.(1) The need to understand the causes of autism and the underlying pathophysiology has become more acute since the number of diagnosed cases has risen markedly.(2) Several recent research studies lend support to the hypothesis that abnormalities involving the plasma Amino Acids profiles have been implicated in the etiology of autism.(3,4) We designed a preliminary prospective cohort study to test plasma amino acids profiles in blood samples from patients with autism and normal cases whose age and gender matched. Twenty nonconsecutive patients admitted at 2 hospitals with a diagnosis of autism confirmed by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). All enrolled patients with autism were newly diagnosed. Twenty nonconsecutive control subjects were randomly selected from the eligible outpatients. All the eligible control subjects were defned as children 2–6 years old who were not known to be autistic or to have any other neurodevelopmental that could be related to autism. The Ethics Committee of China Rehabilitation Research Center, China, approved the trial protocol. All subjects’ parents provided informed consent. Fasting blood samples were drawn on days 1 (admission) and then were immediately centrifuged and stored at −80°C. The plasma amino acids profiles were assayed using aTRAQTM Kits by Liquid chromatography-tandem mass spectrometry. Plasma neurotransmitter (including dopamine, noradrenalin and adrenalin) were also tested using radioimmunoassay. Results were presented as means ± standard deviation (SD). Student’s unpaired t test was used to compare the values in normal and autistic children. Statistical significance was defined as p<0.05. The mean age of the 20 patients was 3.46 ± 0.56 years; 17 were boy. Three patients had family history of autism. The median length of hospital stay was 86 days (18–321 days). The mean hospitalization expense was 64.6 ± 5.8 US dollars per day. On admission, the results indicated that the mean plasma lysine, glutamic acid and homocysteine levels were significantly (p<0.05) higher in autism as compared to controls while plasma leucine, tryptophan, valine, taurine, tyrosine and glutamine levels were lower in autism than control group (p<0.05) (Table 1). However, there was no difference in plasma other amino acids levels between autism and control group. In addition, we observed that the plasma dopamine, noradrenalin and adrenalin were significantly higher in the autistic group compared to controls (p<0.05). Table 1. Table 1 Plasma amino acids profiles and neurotransmitter in children with autism and normal These preliminary results confirm an important conclusion: children with autism are significantly more likely to have abnormal in amino acids metabolim. Those may be caused by gastrointestinal problems as well as picky eating and selective eating in their children.(5) This raises serious concerns regarding the long term effects of supervised restricted diets or nutritional supplement in children with autism. Whiteley et al.(6) reported that dietary intervention may positively affect developmental outcome for some children diagnosed with autism. Thus, further investigation in Chinese autism required to measure the effectiveness of diet related treatments on improving the clinical symptoms of autism. In addition, elevated levels of various neurotransmitters (including dopamine, noradrenalin and adrenalin) have been observed in autistic group compared to controls. The relationships between autism and plasma neurotransmitter should be further explored.

Status of B-Vitamins and Homocysteine in Diabetic Retinopathy: Association with Vitamin-B12 Deficiency and Hyperhomocysteinemia

Diabetic retinopathy (DR) is a common cause of blindness. Although many studies have indicated an association between homocysteine and DR, the results so far have been equivocal. Amongst the many determinants of homocysteine, B-vitamin status was shown to be a major confounding factor, yet very little is known about its relationship to DR. In the present study, we, therefore, investigated the status of B-vitamins and homocysteine in DR. A cross-sectional case–control study was conducted with 100 normal control (CN) subjects and 300 subjects with type-2 diabetes (T2D). Of the 300 subjects with T2D, 200 had retinopathy (DR) and 100 did not (DNR). After a complete ophthalmic examination including fundus fluorescein angiography, the clinical profile and the blood levels of all B-vitamins and homocysteine were analyzed. While mean plasma homocysteine levels were found to be higher in T2D patients compared with CN subjects, homocysteine levels were particularly high in the DR group. There were no group differences in the blood levels of vitamins B1 and B2. Although the plasma vitamin-B6 and folic acid levels were significantly lower in the DNR and DR groups compared with the CN group, there were no significant differences between the diabetes groups. Interestingly, plasma vitamin-B12 levels were found to be significantly lower in the diabetes groups compared with the CN group; further, the levels were significantly lower in the DR group compared with the DNR group. Higher homocysteine levels were significantly associated with lower vitamin-B12 and folic acid but not with other B-vitamins. Additionally, hyperhomocysteinemia and vitamin-B12 deficiency did not seem to be related to subjects' age, body mass index, or duration of diabetes. These results thus suggest a possible association between vitamin-B12 deficiency and hyperhomocysteinemia in DR. Further, the data indicate that vitamin-B12 deficiency could be an independent risk factor for DR.

Analysis of perinatal outcome by combination of first trimester maternal plasma homocysteine with uterine artery Doppler velocimetry

To analyse the pregnancy outcome by combining plasma homocysteine with uterine artery Doppler velocimetry at 11 to 14 weeks of gestation. A prospective cohort study with 103 healthy pregnant women. Uterine artery Doppler velocimetry was performed at between 11 and 14 weeks of gestation. Abnormal blood flow was defined as average pulsatility index >1.5 and presence of unilateral or bilateral diastolic notch. Doppler scores were calculated by a modified scoring method of uterine artery flow velocity waveforms. Serum for measurement of homocysteine, vitamin B(12) and folate levels were collected when the ultrasonographic measurement was performed. Pre-eclampsia developed in five, gestational hypertension in three, intrauterine growth restriction in two and preterm birth in eight patients. There was a significant difference between mean plasma homocysteine levels at different Doppler scores (p<0.001) and a weak positive correlation between Doppler scores and occurrence of pregnancy complications (r(s) = 0.232, p<0.05). Mean homocysteine level increased with increasing Doppler scores. Any uterine artery abnormality had a sensitivity of 88.9% in predicting obstetric complications. Addition of hyperhomocytenemia to Doppler scores did not change the sensitivity. Maternal serum homocysteine level is increased in 11 to 14 weeks of gestation that is complicated with pre-eclampsia, gestational hypertension, intrauterine growth restriction and preterm birth. Addition of homocysteine determination to uterine artery Doppler in the first trimester does not add any advantage in predicting adverse perinatal outcome.

Meta-analysis: hyperhomocysteinaemia in inflammatory bowel diseases

The magnitude of association between homocysteine metabolism and inflammatory bowel diseases (IBD) remains unknown, whereas the association between hyperhomocysteinaemia and thrombosis remains controversial in IBD. To conduct a systematic review and meta-analysis to examine these issues. The literature search was conducted using MEDLINE database and international conference abstracts from January 1966 to April 2011 and included all studies that evaluated plasma homocysteine level in IBD. Twenty-eight studies evaluated the plasma homocysteine level and/or hyperhomocysteinaemia risk in IBD patients. Five studies assessed the association of hyperhomocysteinaemia with thrombosis. The mean plasma homocysteine level was significantly higher in IBD patients when compared with controls (weighted mean difference (WMD)=3.75 μmol/L; 95% CI, 2.23-5.26 μmol/L; P<0.0001; reference ranges for plasma homocysteine level: 5-12 μmol/L). The mean plasma homocysteine level did not differ between ulcerative colitis (UC) and Crohn's disease (CD) (WMD=0.41 μmol/L; 95% CI, -2.45 to 3.06 μmol/L; P=0.76). The risk of hyperhomocysteinaemia was significantly higher in IBD patients when compared with controls [odds ratio (OR)=4.65; 95% CI, 3.04-7.09; P<0.0001]. The risk of hyperhomocysteinaemia was not higher among IBD patients who experienced thromboembolic complications (OR=1.97; 95% CI, 0.83-4.67; P=0.12). Plasma folate level was inversely correlated with IBD risk associated with MTHFR C677T polymorphism (P=0.006). The risk of hyperhomocysteinaemia is significantly higher in IBD patients when compared with controls. The risk assessment of hyperhomocysteinaemia-related thrombosis in IBD requires further investigation. Deficient folate status is associated with a higher impact of MTHFR C677T polymorphism on IBD risk.

Association of MTHFR A1298C polymorphism (but not of MTHFR C677T) with elevated homocysteine levels and placental vasculopathies

Our aim in this study was to investigate the association between elevated homocysteine levels and the two MTHFR polymorphisms, C677T and A1298C, with several pregnancy complications such as recurrent pregnancy loss, preeclampsia, placental abruption and intrauterine growth retardation. In 203 women with different placental vasculopathies, we determined the MTHFR C677T and the A1298C prevalence and their relative association to elevated homocysteine levels. The mean plasma homocysteine level was significantly higher in the pathologic groups when compared with the control group. We identified the carriage of the MTHFR A1298C polymorphism as a significant risk factor for vascular-related pregnancy complications. Women with MTHFR A1298C polymorphism or elevated homocysteine levels have an increased risk of placental vasculopathies. The MTHFR A1298C mutation also had a positive impact on elevated homocysteine levels. The lack of association between the MTHFR C677T polymorphism and pregnancy morbidities needs further studies.

The role of methylenetetrahydrofolate reductase C677T polymorphism on the peripheral blood natural killer cell proportion in women with unexplained recurrent miscarriages

ObjectiveTo 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.MethodsA 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.ResultsNo differences were found between the two groups' mean plasma homocysteine levels (7.6±1.5 µmol/L vs. 7.1±2.1 µmol/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±1.1 µmol/L) had higher homocysteine levels than those with the CC and CT variants (7.4±1.9 µmol/L and 7.4±1.2 µmol/L) and those with the CT variant (19.2±8.1%) had a higher proportion of CD3-/CD56+ pbNK cells than those with the CC and TT variants (17.7±6.6% and 17.9±7. 0%), but the results of both comparisons were statistically insignificant.ConclusionThese 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.

Plasma homocysteine level in patients with Behcet's disease with or without thrombosis.

To find the possible role of plasma homocysteine level as a contributing factor in venous and arterial thrombosis in patients with Behcet's disease (BD). In a case control study, two groups of BD patients were included: 47 with thrombosis and 49 without thrombosis. All patients fulfilled the International Study Group Criteria for BD and the confirming diagnostic procedures for vascular thrombosis were either Doppler sonography or angiography. Forty-nine controls were selected by consecutive sampling among age and sex matched healthy subjects. Plasma homocysteine level was measured by ELISA in all. The clinical and laboratory characteristics of the disease were compared between the two groups of BD patients. Comparisons were done by ANOVA and Chi square tests; correlations were analyzed with Pearson test. The mean plasma homocysteine level was significantly higher in BD patients (14.9±13.9 μMol/L) than in healthy controls (9.9±6.7 μMol/L), P<0.02. The difference was also significant when comparing the three groups by ANOVA: BD patients with thrombosis (24.2±13.2 μMol/L), BD patients without thrombosis (5.9±7.0 μMol/L), and healthy controls (P<0.0001). We found no correlation between plasma homocysteine level and any organ involvement other than thrombosis. The mean plasma homocysteine level was lower in HLA-B51 positive BD patients (11.6±12.1 vs. 21.7±16.3 μMol/L, P<0.05), but the difference was not significant in those with thrombosis (20.9±13.2 vs. 29.5±12.7 μMol/L, P=0.18). Hyperhomocysteinaemia may be an independent risk factor for vascular thrombosis in patients with BD. This is the first study showing a negative correlation between HLA-B51 and plasma homocysteine level.