Hyperhomocysteinaemia is an independent risk factor for peripheral arterial disease in a Chinese Han population.

BACKGROUND AND AIMS: Hyperhomocysteineamia (HHcy) has long been suggested as a risk factor for atherosclerosis. However, the association between HHcy and peripheral arterial disease (PAD) is still controversial. There is a lack of research on this topic in the Chinese population. This study aims to provide further results. METHODS: 240 PAD patients and 240 control subjects were evaluated for both serum total homocysteine levels and ankle brachial indexes (ABIs). Multivariable logistic regression models were used to estimate the association between HHcy and the risk of developing PAD. Interaction and stratified analyses were conducted according to age, sex, smoking status, drinking status, and histories of chronic disease. RESULTS: The multivariate logistic regression analyses revealed that the risk of PAD was significantly associated with serum homocysteine levels. The interaction analysis showed no interactive role in the association between HHcy and PAD, indicating that homocysteine was associated with PAD independently of classical vascular risk factors. CONCLUSIONS: In conclusion, HHcy is an independent risk factor for PAD in the Chinese Han population. A prospective and randomized clinical trial of homocysteine lowering therapy in the Chinese population is needed to assess the causal nature of the relationship.

Hyperhomocysteinaemia is an independent risk factor of abdominal aortic aneurysm in a Chinese Han population.

The associations between hyperhomocysteinaemia (HHcy), methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, and abdominal aortic aneurysm (AAA) remain controversial, with only few studies focused on these associations within the Chinese population. We performed subgroup and interaction analyses in a Chinese Han population to investigate these associations. In all, 155 AAA patients and 310 control subjects were evaluated for serum total homocysteine levels and MTHFR C677T polymorphisms. Multiple logistic regression models were used to evaluate the aforementioned associations. Interaction and stratified analyses were conducted according to age, sex, smoking status, drinking status, and chronic disease histories. The multiple logistic analyses showed a significant association between HHcy and AAA but no significant association between MTHFR C677T polymorphism and AAA. The interaction analysis showed that age and peripheral arterial disease played an interactive role in the association between HHcy and AAA, while drinking status played an interactive role in the association between MTHFR C677T polymorphism and AAA. In conclusion, HHcy is an independent risk factor of AAA in a Chinese Han population, especially in the elderly and peripheral arterial disease subgroups. Longitudinal studies and clinical trials aimed to reduce homocysteine levels are warranted to assess the causal nature of these relationships.

Serum homocysteine level is positively associated with chronic kidney disease in a Taiwan Chinese population.

BACKGROUND: Both hyperhomocysteinemia and chronic kidney disease (CKD) increase risk of cardiovascular disease. In this study, we investigated the association between serum homocysteine level and CKD. MATERIALS AND METHODS: A total of 1,581 participants were recruited from a health check-up center in a tertiary hospital in Taiwan between 2006 and 2008. Two groups were created based on serum homocysteine levels above or below 12.24 µmol/l. Estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease equation; we defined CKD as an eGFR below 60 ml/min/1.73 m(2). Multivariate logistic and linear regression analyses were used to estimate the associations between serum homocysteine levels and kidney function. RESULTS: Subjects with elevated homocysteine levels were older and had higher body mass index, blood pressures, fasting plasma glucose, total cholesterol, triglycerides, and eGFR than those with normal serum homocysteine level. Using multiple logistic regression analyses after adjustment for age, sex, lifestyle habits (smoking, alcohol consumption, and betel nut chewing) and chronic diseases (hypertension, diabetes, dyslipidemia), the odds ratio (95 % confidence interval) of having CKD was 5.76 (2.99-11.1) among subjects with elevated serum homocysteine levels compared to subjects with normal serum homocysteine levels. The significant increase in odds ratios for CKD in progressive homocysteine levels reveals a dose-response effect. After adjustment for confounders, at multiple linear regression analyses serum homocysteine level resulted significantly and negatively correlated to eGFR. CONCLUSIONS: Elevated serum homocysteine levels appear to be closely associated with CKD. Serum homocysteine levels are negatively associated with eGFR.

Association of polymorphisms on chromosome 9p21.3 region with increased susceptibility of abdominal aortic aneurysm in a Chinese Han population.

OBJECTIVE: Several studies have reported that polymorphisms on chromosome 9p21.3, near the CDKN2A/2B gene, are strongly associated with increased susceptibility to abdominal aortic aneurysm (AAA). However, no convincing data has been reported on a relationship between AAA and these variants in the Chinese Han population. The aim of this study was to evaluate the role of rs10757278 and rs1333049 in determining genetic susceptibility to AAA. METHODS: A total of 155 AAA patients and 310 controls, comparable in age and gender, were enrolled in this study. DNA samples were genotyped for rs10757278 and rs1333049 using the MassArray system. The association between these two single nucleotide polymorphisms and AAAs was tested using multivariate logistic regression. Stratified analysis was also performed by clinical and laboratory features. RESULTS: Single nucleotide polymorphisms rs10757278 and rs1333049 were significantly associated with increased risk of AAA. The frequencies of rs10757278-G and rs1333049-C in AAA patients were significantly higher than in control subjects (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.11-2.11; P = .01, and OR, 1.48; 95% CI, 1.07-2.05; P = .02). Multiple logistic regression analysis indicated that, after adjusting for smoking habits, drinking habits, and histories of other chronic diseases, homozygosity of the risk allele for rs10758278-G and rs1333049-C also increased the likelihood of AAA (OR, 2.31; 95% CI, 1.22-4.36, and OR, 2.14; 95% CI, 1.13-4.05). The frequency of the GC haplotype was significantly higher in AAA patients than in control subjects (OR, 1.44; P = .038). Stratification analysis of clinical and laboratory features revealed no association between polymorphisms and aortic diameters in AAA patients. There was a significantly high frequency of the rs10757278 GG genotype in AAA patients with high serum total homocysteine compared with those control subjects with high serum total homocysteine (OR, 2.71; 95% CI, 1.12-6.58; P = .03) indicating that the genotype GG of rs10757278 might interact with the homocysteine biological pathway to stimulate the presence of AAA. CONCLUSIONS: Present data demonstrate that rs10757278 and rs1333049 on chromosome 9p21.3 are significantly associated with increased risk of AAA in the Chinese population and emphasize the need to further study the role of these markers in AAA.

Daily milk intake improves vitamin B-12 status in young vegetarian Indians: an intervention trial.

BACKGROUND: Asymptomatic Indian lacto vegetarians, who make up more than half of the Indian population in different geographic regions, have distinctly low vitamin B-12 concentrations than non- vegetarians. Vegetarians consume milk but it seems that the amount is not enough to improve vitamin B-12 status or vitamin B-12 concentration in milk itself may be low. The aim of this study was to determine if daily milk consumption can improve vitamin B-12 status. METHODS: Fifteen male and 36 female, young healthy post-graduate volunteers participated. Blood from ten participants (4 males and 6 females) was collected (day-1). They continued their regular diet for next fourteen days and on day-15, blood of all 51 participants was collected, plasma vitamin B-12 concentration was measured and were divided into two groups; Normal (vitamin B-12 >148 pmol/L, n = 22) and Vitamin B-12 deficient (<148 pmol/L, n = 29), the remaining plasma was stored. All participants consumed 600 ml. of non-enriched buffalo milk (200 × 3) during the day along with their usual diet. Next day blood was collected for plasma holotranscobalamin II measurement. Subjects from deficient group continued to drink 400 ml of milk daily for next 14 days and blood was collected on day-30. Plasma holotranscoabalamin II (day-1, 15, 16, 30), vitamin B-12, folate, total homocysteine, creatinine and hematoloical parameters (day-1, 15, 30), and milk vitamin B-12 concentrations (day-15, 16, 30) were measured. RESULTS: Fifty seven per cent of the participants were vitamin B-12 deficient and 65% were hyperhomocysteinemic. No significant difference in biomarkers was observed when there was no intervention. Plasma holotranscobalamin II concentration increased from 19.6 to 22.27 pmol/L (p < 0.0001) 24 hrs after milk load in the whole group. Plasma vitamin B-12 increased from 92.5 to 122 pmol/L and tHcy concentrations decreased from 31.9 to 24.9 µ mol/L (p < 0.0001 for both) 14 days after regular milk intake in vitamin B-12 deficient subjects. CONCLUSIONS: Regular intake of milk improved vitamin B-12 status of vitamin B-12 deficient vegetarians indicating a potential dietary strategy to improve the vitamin status.

Prevalence of hyperhomocysteinaemia and its major determinants in rural Chinese hypertensive patients aged 45-75 years.

We aimed to investigate the prevalence of hyperhomocysteinaemia (total plasma homocysteine (tHcy) ≥ 10 µmol/l) and its major determinants in rural Chinese hypertensive patients. A cross-sectional investigation was carried out in Lianyungang of Jiangsu province, China. This analysis included 13 946 hypertensive adults. The prevalence of hyperhomocysteinaemia was 51.6 % (42.7 % in women and 65.6 % in men). The OR of hyperhomocysteinaemia were 1.52 (95 % CI 1.39, 1.67) and 2.32 (95 % CI 2.07, 2.61) for participants aged 55-65 and 65-75 v. 45-55 years; 1.27 (95 % CI 1.18, 1.37) for participants with a BMI ≥ 25 v. < 25 kg/m²; 1.14 (95 % CI 1.06, 1.23) for participants with v. without antihypertensive treatment; 1.09 (95 % CI 1.00, 1.18) for residents inland v. coastal; 0.89 (95 % CI 0.82, 0.97) and 0.83 (95 % CI 0.74, 0.92) for participants with moderate and high v. low physical activity levels; 1.54 (95 % CI 1.41, 1.68) and 2.47 (95 % CI 2.17, 2.81) for participants with a glomerular filtration rate 60-90 and < 60 v. ≥ 90 ml/min per 1.73 m²; and 1.20 (95 % CI 1.07, 1.35) and 3.81 (95 % CI 3.33, 4.36) for participants with CT and TT v. CC genotype at methylenetetrahydrofolate reductase 677C>T polymorphism, respectively. Furthermore, higher tHcy concentrations were observed in smokers of both sexes (men: geometric mean 12.1 (interquartile range (IQR) 9.2-14.5) v. 11.9 (IQR 9.-14.) µmol/l, P= 0.005; women: geometric mean 10·3 (IQR 8.3-13.0) v. 9.6 (IQR 7.8-11.6) µmol/l, P= 0.010), and only in males with hypertension grade 3 (v. grade 1 or controlled blood pressure) (geometric mean 12.1 (IQR 9.2-14.4) v. 11.7 (IQR 9.2-14.0), P= 0.016) and in male non-drinkers (yes v. no) (geometric mean 12.3 (IQR 9.4-14.8) v. 11.7 (IQR 9.1-13.9), P= 0.014). In conclusion, there was a high prevalence of hyperhomocysteinaemia in Chinese hypertensive adults, particularly in the inlanders, who may benefit greatly from tHcy-lowering strategies, such as folic acid supplementation and lifestyle change.

Folate and vitamin B12 deficiency and hyperhomocysteinemia promote oxidative stress in adult type 2 diabetes.

OBJECTIVE: The purpose of this study was to examine the status of folate and vitamin B12 (B12) in relation to serum homocysteine (HCY) and oxidative stress indices in patients with type 2 diabetes (T2DM). METHODS: This case-control study involved 100 Omani adults (50 patients newly diagnosed with T2DM and 50 age- and gender-matched healthy controls). Several parameters were investigated, including dietary intake and biochemical assessments of folate, B12, HCY, oxidative stress markers (glutathione and total antioxidant status), and antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and catalase). RESULTS: Low serum levels of folate, B12, and hyperhomocysteinemia were prevalent in patients with T2DM compared with controls. Oxidative stress was evident in patients with T2DM as indicated by low serum levels of glutathione, total antioxidant status, and impaired antioxidant enzymatic activities (superoxide dismutase, glutathione peroxidase, and catalase). CONCLUSION: The low intake of folate and B12 is associated with low serum levels of these two nutrients and hyperhomocysteinemia in Omani adults with T2DM.

The incidence of raised procoagulant factors and hyperhomocysteinaemia in Chinese patients with chronic venous insufficiency.

BACKGROUND: For reasons that are poorly understood, there appear to be differences in the prevalence of chronic venous insufficiency (CVI) and venous thromboembolism between Caucasians and Asians. OBJECTIVES: To compare levels of procoagulant factors and homocysteine (Hcy) in Hong Kong (HK) Chinese and United Kingdom (UK) Caucasian populations of patients with CVI (patients of CEAP clinical stages C4 - C6). METHODS: HK Chinese and UK Caucasian patients with CEAP clinical grade 4-6 venous disease were enrolled. Patients with conditions known to be associated with thrombophilia (TP) were excluded. UK and HK patients were matched by gender, age (within 5 years) and by CEAP clinical grade. All subjects underwent clinical examination, venous duplex ultrasound, and measurement of Hcy and factors (F) VIII, IX and XI. RESULTS: 63 Patients were enrolled in each group: Mean age 64y (HK group); 67y (UK group). 37% were female; 19% had active venous ulceration. One-third of patients in each group had deep venous reflux. High Hcy, FIX and FXI were significantly more common in the UK group. Multiple TP was more common in the UK group: raised levels of >or=2 factors in 26 vs. 14 patients (P = 0.022, chi(2)). Median Hcy (14.3 vs. 10.8 micromol/L; P < 0.0005, Wilcoxon signed rank [WSR]), FIX (131 vs. 115%; P = 0.048), and FXI (114 vs. 97%; P = 0.002) were significantly higher in the UK group. There was no significant difference in FVIII levels. CONCLUSIONS: Raised procoagulant factors were more common in Caucasians compared with Chinese patients with CVI in this study. As with the inherited thrombophilias, the pattern of raised procoagulant factors in Chinese patients appears to differ from that in Caucasians.

Ethnicity and risk factors for change in the ankle-brachial index: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: The aim of this study was to determine the risk factors for conversion from a normal to either a low or high ankle-brachial index (ABI). METHODS: Participants in the Multi-Ethnic Study of Atherosclerosis who had two separate measurements of the ABI over a 3-year time period were assessed. RESULTS: At baseline, the mean age was 62 years and 50% were women, 28% African American, 12% Chinese, 22% Hispanic and 38% non-Hispanic White. Of the 5514 participants with a baseline ABI between 0.90 and 1.40, 89 (1.6%) had an ABI < or = 0.90 ("low ABI group") and 71 (1.3%) had an ABI > or = 1.40 ("high ABI group") 3 years later. On multivariable analysis, the odds for having progressed into the low ABI group were significantly increased for higher baseline age, hypertension, diabetes, greater pack-years of cigarette smoking, and homocysteine levels. The odds for progression into the high ABI group were increased for male gender and higher body mass index. Compared with non-Hispanic Whites, African Americans had a significantly higher odds for progression to the low ABI group (odds ratio [OR]: 2.24, 95% confidence interval [CI]: 1.29-3.88) while having a reduced odds for progression to the high ABI group (OR: 0.50, 95% CI: 0.24-1.00). Neither Chinese nor Hispanic ethnicity was significantly associated with progression to either ABI group. CONCLUSIONS: The risk factors for progression to a low or high ABI were distinct and African Americans were at increased risk for progression to a low ABI but at decreased risk for progression into the high ABI group.

Exploratory study of plasma total homocysteine and its relationship to short-term outcome in acute ischaemic stroke in Nigerians.

BACKGROUND: Hyperhomocysteinemia is a potentially modifiable risk factor for stroke, and may have a negative impact on the course of ischaemic stroke. The role of hyperhomocysteinemia as it relates to stroke in Africans is still uncertain. The objective of this study was to determine the prevalence and short-term impact of hyperhomocysteinemia in Nigerians with acute ischaemic stroke. We hypothesized that Hcy levels are significantly higher than in normal controls, worsen stroke severity, and increase short-term case fatality rates following acute ischaemic stroke. METHODS: The study employed both a case-control and prospective follow-up design to study hospitalized adults with first - ever acute ischaemic stroke presenting within 48 hours of onset. Clinical histories, neurological evaluation (including National Institutes of Health Stroke Scale (NIHSS) scores on admission) were documented. Total plasma Hcy was determined on fasting samples drawn from controls and stroke cases (within 24 hours of hospitalization). Outcome at 4 weeks was assessed in stroke patients using the Glasgow Outcome Scale (GOS). RESULTS: We evaluated 155 persons (69 acute ischaemic stroke and 86 healthy controls). The mean age +/- SD of the cases was 58.8 +/- 9.8 years, comparable to that of controls which was 58.3 +/- 9.9 years (T = 0.32; P = 0.75). The mean duration of stroke (SD) prior to hospitalization was 43.5 +/- 38.8 hours, and mean admission NIHSS score was 10.1 +/- 7.7. Total fasting Hcy in stroke patients was 10.2 +/- 4.6 umol/L and did not differ significantly from controls (10.1 +/- 3.6 umol/L; P = 0.88). Hyperhomocysteinemia, defined by plasma Hcy levels > 90th percentile of controls (>14.2 umol/L in women and >14.6 umol/L in men), was present in 7 (10.1%) stroke cases and 11 (12.8%) controls (odds ratio 0.86, 95% confidence interval 0.31 - 2.39; P > 0.05). In multiple regression analysis admission NIHSS score (but not plasma Hcy) was a significant determinant of 4 week outcome measured by GOS score (P < 0.0001). CONCLUSION: This exploratory study found that homocysteine levels are not significantly elevated in Nigerians with acute ischaemic stroke, and admission Hcy level is not a determinant of short-term (4 week) stroke outcome.

Association of increased levels of homocysteine and peripheral arterial disease in a Japanese-Brazilian population.

OBJECTIVES: Our aim was to evaluate the possible association between homocysteine levels and peripheral arterial disease (PAD) in a population-based study of Japanese-Brazilians. MATERIALS AND METHODS: This cross-sectional study was derived from a population-based survey on the prevalence of diabetes and associated diseases conducted in Japanese-Brazilians. A total of 1330 male and female subjects aged>or=30 years were submitted to clinical examination and laboratory procedures including homocysteine measurement. The ankle-brachial index (ABI) was calculated; subjects with ABI values <0.9 were diagnosed with PAD. The evaluable population included 1008 subjects. Logistic regression was used taking PAD as the dependent variable. RESULTS: Mean age of the population was 56.5 years and overall prevalence of PAD was 20%. A worse cardiovascular profile was found in male patients, including significantly higher homocysteine levels (11.9+/-1.8 vs. 9.1+/-1.1micromol/L, p<0.001). Men with PAD had higher prevalence rates of hyperhomocysteinemia compared to women (22.7% vs 7.6%). Univariate analysis showed an odds ratio of hyperhomocysteinemia for PAD of 1.51 [1.02-2.25] in men and 1.69 [1.06-2.68] in women. After adjustment for other cardiovascular risk factors, higher levels of homocysteine were only significantly related to PAD in men. CONCLUSION: In a Japanese-Brazilian population, elevated levels of homocysteine are associated with PAD in men. Prospective studies are necessary to confirm this finding.

Hyperhomocysteinemia and low methionine stress are risk factors for central retinal venous occlusion in an Indian population.

PURPOSE: The underlying cause of disturbed homocysteine metabolism is incompletely understood in young persons with central retinal vein occlusion (CRVO) with mild hyperhomocysteinemia (HHcys) and no other systemic disease in India. A 2-year prospective study was undertaken to determine whether HHcys is a risk factor for CRVO in an Indian population. METHOD: The prevalence of fasting HHcys was evaluated in a consecutive series of 29 patients with CRVO (mean age, 30 +/- 6 years) along with 57 age- and sex-matched control subjects (healthy subjects, mean age 27 +/- 5 years). Strict inclusion and exclusion criteria were used. Plasma levels of homocysteine (Hcys), methionine, cysteine, glutathione, B(12), and folate were measured. Multivariate logistic regression analysis was performed to determine the risk factors for CRVO. RESULT: Fifteen of 29 patients with CRVO (51.72%) exhibited HHcys (>15 muM). The mean Hcys level was significantly elevated in the patients with CRVO (19.1 +/- 13.1 muM) compared with that in the healthy control subjects (14.7 +/- 6.2 muM) with P = 0.04. The increased Hcys levels in CRVO cases was associated with decreased methionine (P = 0.052) and decreased B(12) (P = 0.001). A multivariate logistic regression analysis revealed an odds ratio of 1.9 (95% CI = 0.50-7.16) for Hcys and 15.9 for methionine (95%CI = 1.50-169.62; P = 0.022). CONCLUSION: Elevated Hcys and low methionine were risk factors for CRVO in an Indian population.

Novel genomic loci influencing plasma homocysteine levels.

BACKGROUND AND PURPOSE: Genetic factors that influence interindividual variation in levels of plasma homocysteine, a risk factor for vascular disease, are not fully understood. We performed linkage analyses to identify genomic regions that influence homocysteine levels in blacks and non-Hispanic whites. METHODS: Subjects (n=2283) belonged to hypertensive sibships and included 1319 blacks (63+/-10 years, 70% women) and 964 non-Hispanic whites (61+/-7 years, 57% women). Fasting plasma homocysteine was measured by high-pressure liquid chromatography. Genotypes were measured at 366 microsatellite marker loci distributed across the 22 autosomes. Plasma homocysteine adjusted for age, sex, body mass index, serum creatinine, and estrogen use (in women) was used in the genetic analyses. Heritability and linkage analyses were performed using a variance components approach. RESULTS: Mean (+/-SD) homocysteine levels were 10.4+/-5.27 mumol/L in blacks and 10.0+/-2.84 micromol/L in non-Hispanic whites (P=0.58 for difference). Homocysteine levels were significantly (P<0.0001) heritable in blacks (h2=0.70) and in non-Hispanic whites (h2=0.49). Linkage analyses demonstrated significant evidence of linkage (multipoint logarithm of odds> or =3.0) for homocysteine on chromosomes 1q42, 14q32, and 19p13 in blacks and on chromosomes 9q34 and 12q24 in non-Hispanic whites. Tentative evidence of linkage (logarithm of odds 1.3 to 2.0) was present on chromosomes 2q32, 7p15, 8q24, 18q21, and 20p12 in blacks and chromosomes 6q26 and 18q21 in non-Hispanic whites. Four genes in the homocysteine metabolism pathway (MTR, DNMT1, GAMT, and CARM1) were present under 2 of the significant linkage signals in blacks (chromosomes 1q42 and 19p13). CONCLUSIONS: Plasma homocysteine is a significantly heritable trait. Linkage analyses reveal several unique genomic loci that may influence circulating levels of homocysteine and therefore susceptibility to vascular diseases including stroke.

Hyperhomocysteinemia and low plasma folate as risk factors for central retinal vein occlusion: a case-control study in a Chinese population.

PURPOSE: To determine whether hyperhomocysteinemia and low plasma folate are risk factors for central retinal vein occlusion (CRVO) in the Chinese population. METHODS: A matched case-control study was conducted between July 2004 and May 2005. The study cohort consisted of 64 individuals that had been diagnosed to have CRVO and 64 normal controls (matched for age, gender, hypertension, smoking and drinking habits). None of the cases or controls had a history of diabetes, glaucoma, medication or any other vascular events that might minimize the influence on plasma homocysteine levels. A cross-sectional analysis among the 64 cases was performed to compare the prevalence of hyperhomocysteinemia and low plasma folate among subjects with and without ischemia and subjects with age above 45 and below 45 years. Plasma homocysteine level was measured by means of high-performance liquid chromatography and plasma folate concentration by radioimmunoassay. RESULTS: The CRVO patients had a significantly higher homocysteine level (13.83+/-1.71 micromol/l) than the normal controls (8.05+/-0.58 micromol/l; p=0.003). The plasma folate levels were significantly lower in CRVO patients than in controls (5.62+/-0.39 ng/dl vs 7.23+/-0.60 ng/dl; p=0.032). A 1 micromol/l increase of plasma homocysteine level was associated with an odds ratio of 1.368. Hyperhomocysteinemia was defined as a homocysteine level of >14.97 micromol/l and was seen in 11 patients in the ischemic group, significantly more often than in the non-ischemic group (5 patients; p=0.030). CONCLUSIONS: The results suggest that hyperhomocysteinemia and low plasma folate are independent risk factors for CRVO and are associated with the development of CRVO in the Chinese population.

Serum total homocysteine levels and the prevalence of folic acid deficiency and C677T mutation at the MTHFR gene in an indigenous population of Amazonia: the relationship of homocysteine with other cardiovascular risk factors.

Hyperhomocysteinemia is a risk factor for cardiovascular disease. C677T mutation at the MTHFR gene and deficiencies of folic acid and vitamin B-12 may account for elevation of total homocysteine (tHcy). Ninety Brazilian Parkatêjê Indians (90.0% of the population without admixture, aged > or = 20 years) were studied. Hyperhomocysteinemia was observed in 26.7% of the Indians. No case of vitamin B-12 deficiency was detected. Folic acid deficiency was found in 43.3% of the subjects. Rates of mutated allele 677T and TT genotype were 40.7% and 14.0%, respectively. Prevalence of hypertension, dyslipidemia, smoking, WHR > or = 0.9, BMI > or = 25 kg/m2 and chronic alcohol use were 4.4%, 44.4%, 25.6%, 72.2%, 67.8%, and 0.0%, respectively. All creatinine values were normal. Natural logarithmic (ln) tHcy showed no correlation with age, but was positively correlated with systolic (r = 0.22) and diastolic (r = 0.21) blood pressure and triglycerides (r = 0.39) and inversely correlated with folic acid (r = -0.40) adjusted for age and sex. Total homocysteine (tHcy) was higher among TT genotype (P < .001). The multiple linear regression model, containing variables for sex, folic acid, TT genotype, and triglycerides, explained 50.0% of the variation of the ln tHcy. In summary, high rates of cardiovascular risk factors were discovered. C667T mutation and folic acid deficiency can explain, at least in part, the observed hyperhomocysteinemia.

Serum total homocysteine levels, folate, and B-vitamins intake and coronary heart disease risk factors among tri-ethnic college students.

The main objective of our study was to determine and compare total serum homocysteine (tHcy) levels among tri-ethnic college students. The 180 tri-ethnic subjects completed Cardiovascular Risk Assessment questionnaires, and gave 15 mL fasting blood for serum tHcy and blood lipid analysis. The mean tHcy (+/- SD) of the all subjects was 6.33 +/- 3.15 micromol/L. Male subjects had significantly (P=.001) higher serum tHcy levels compared with female subjects. Black non-Hispanic females and Hispanic females showed significantly (P=.003) lower tHcy levels than White non-Hispanic females. Moderate elevations of tHcy levels were strongly related to cigarette smoking, physical inactivity, behavioral style, high blood pressure, and low intakes of folate, and vitamins B6 and B12. A positive association of tHcy levels with cardiovascular heart disease (CHD) risk point standards was observed in females (P=.001), Hispanic (P=.001), Hispanic males (P=.049), Hispanic females (P=.009), and Black non-Hispanic females (P=.005). We observed gender and ethnic differences in tHcy levels of this young population with normal tHcy levels. Abnormally high tHcy concentrations appear to be acquired later in life.

Homocysteine and its nutritional determinants in two ethnic groups of Slovakia.

Determinants of total homocysteine involve demographic (age, sex, ethnic origin), genetic (enzymatic defects of metabolic homocysteine pathways) and acquired factors (deficiency of B-group vitamins, state of health, lifestyle). Plasma levels of total homocysteine and serum levels of vitamin B12, folic acid, vitamin B6 were measured in adult apparently healthy Romany minority subjects (n=119) and compared with those levels in apparently healthy subjects of majority Slovak population (n=146). Mean homocysteine level was similar in both groups (9.92 micromol/l in the Romany vs. 9.61 micromol/l in majority group). Hyperhomocysteinemia was only observed in 3% of both ethnic probands. Vitamin B12 level was equal (301 micromol/l in the Romany and 311 micromol/ in majority group). Deficient levels were found in 4% of the Romany subjects and 9% of the majority subjects. Folic acid level was significantly lower in Romany group (11.3 nmol/l vs. 14.8 nmol/l) with deficiency in 42% of the Romany subjects vs. 28% in the majority subjects. This finding is a consequence of lower consumption of fruit, vegetables, pulses and whole grain products in the Romany group. Vitamin B6 deficiency was found in 68% of the Romany subjects and 40% of majority subjects. This vitamin is homocysteine determinant under excessive methionine intake (overnutrition with predominance of animal protein intake). As was demonstrated in a dietetic questionnaires, the Romany subjects are more frequent consumers of meat and eggs. This nutrition regime should indicate an increased homocysteine level under vitamin B6 deficiency. The results of normal homocysteine levels in the Romany population under condition of higher folic acid and vitamin B6 deficiencies, smoking and higher alcohol consumption may suggest a more effective homocysteine metabolism in relation to different ethnic origin.

Hyperhomocysteinemia and vitamin B-12 deficiency are more striking in Syrians than in Germans--causes and implications.

Hyperhomocysteinemia is an accepted risk factor for coronary artery disease, but the determining factors are not fully understood. We investigated hyperhomocysteinemia and vitamin deficiency in Syrian coronary patients and apparently healthy Syrian and German controls. We enrolled 273 Syrian patients with angiographically confirmed stenosis, along with 159 Syrian and 75 German controls. Plasma total homocysteine (HCY), cystathionine, methylmalonic acid (MMA), vitamin B-6, B-12, folate, lipids, apolipoproteins and methylenetetrahydrofolate reductase (C677T-MTHFR) mutation were analysed. There was a very high prevalence of hyperhomocysteinemia (>12 micromol/l) in Syrians (patients 61%, controls 44%, Germans 16%) together with functional vitamin B-12 deficiency diagnosed by elevated MMA (patients 49%, controls 47%, Germans 3%), which was in contrast to the low frequency of decreased serum vitamin B-12 (12% in patients, 7% in Syrian controls). The HCY concentration in German controls was lower than in Syrians, median 8.8 vs. 11.3 micromol/l. The vitamin B-12 deficiency induces folate trapping; higher levels of folate are needed to prevent hyperhomocysteinemia. Germans achieved the HCY level of < or =12 micromol/l at significantly lower folate concentrations > or =4.4 ng/ml, than Syrians with normal MMA (> or =16.7 nmol/l folate) or Syrians with high MMA (> or =23.3 nmol/l folate). Smoking and homozygous state for C677T-MTHFR mutation contributed to hyperhomocysteinemia. We could confirm that the reasons for hyperhomocysteinemia in Syrians were in fact mostly related to a relative folate deficiency, which is due to a vitamin B-12 shortage. Vitamin B-12 deficiency induces folate trapping. Besides lifestyle, other presently unknown factors may contribute to hyperhomocysteinemia and vitamin B-12 deficiency in Syrians.