Hepatitis B Virus Genotypes in the Kingdom of Bahrain: Prevalence, Gender Distribution and Impact on Hepatic Biomarkers.

Background: Approximately 400 million people are infected with Hepatitis B virus (HBV) around the world, which makes it one of the world's major infectious diseases. The prevalence of HBV genotypes and predictive factors for risk are poorly known in the Kingdom of Bahrain. Objectives: The aim of the present study was to investigate the prevalence of HBV genotypes, its correlation with demographic factor sand impacts on hepatic biomarkers. Materials and Methods: Venous blood samples were collected from 82 HBV positive patients (48 males, 34 females). The extraction of HBV DNA, PCR amplification, and genotyping were done to classify different genotypes (A, A/D, B, B/D, C, D, D/E, E). HBV genotypes association with gender, nationality, mode of transmission, and liver cirrhosis complication was determined by descriptive statistic and univariate analysis of variance (ANOVA). For liver function test, unpaired t-test and ANOVA were performed. Results: The predominant genotype among patients under study was genotype D (61%), followed by genotype A (10%), and lowest frequency was found for undetermined genotype (1%). In general, there was no significant association between the different genotypes and some demographical factors, serological investigations, and liver function test. The prevalence of HBV genotypes was higher in male patients as compared to female patients and higher in non-Bahraini than in Bahraini. Patients with the dominant genotype D showed higher than the normal maximum range for alanine aminotransferase (ALT) (mean = 45.89) and Gamma-glutamyl transferase (GGT) (mean = 63.36). Conclusions: The most common HBV genotype in Bahrain was genotype D, followed by genotype A. Further studies involving the sources of transmission and impact of hepatic biomarker in Bahrain are required to enhance the control measures of HBV infections.

Predictors of vitamin D deficiency and insufficiency in adult Bahrainis: a cross-sectional study.

OBJECTIVE: High prevalence of hypovitaminosis D has been reported to be common in different regions of the Middle East. The objective of the present study was to examine the predictors of vitamin D deficiency and insufficiency in Bahrainis. DESIGN: A cross-sectional study. SETTING: Blood transfusion volunteers at a blood bank. SUBJECTS: Serum levels of total 25-hydroxyvitamin D, bone markers and other parameters such age, sex, season and clothing style in the 500 healthy Bahrainis were investigated. RESULTS: In the entire cohort the prevalence of vitamin D deficiency was 49.4% and the relative risk of vitamin D deficiency increased significantly by 1.1, 1.2, 1.5, 1.7 and 1.2 fold with younger age group (P = 0.03), hyperparathyroidism (P = 0.01), low serum Ca (P < 0.001), warm and hot months of the year (P < 0.0001) and female sex (P = 0.002), respectively. In females the prevalence of vitamin D deficiency was 67.6% and the relative risk of vitamin D deficiency increased significantly by 1.1, 1.2, 1.2, 1.2 and 1.4 fold with younger age group (P = 0.04), hyperparathyroidism (P = 0.03), low serum Ca (P = 0.001), warm and hot months of the year (P = 0.001) and conservative clothing style (P = 0.04), respectively. In contrast, in males the prevalence of vitamin D deficiency was 31.2% and the relative risk of vitamin D deficiency was increased by 1.6 fold in warm and hot months of the year (P < 0.0001). CONCLUSIONS: High prevalence of low circulating levels of vitamin D and the relative risk factors associated with vitamin D deficiency and insufficiency observed in the present study suggest an urgent need for public health interventions including vitamin D food fortification in Bahrain.

Association of vitamin D deficiency and hyperparathyroidism with anemia: a cross-sectional study.

Vitamin D deficiency and anemia are common in the Middle East, and vitamin D deficiency and hyperparathyroidism have been reported to be associated with an increased prevalence of anemia. In this study, the hypothesis that vitamin D deficiency and hyperparathyroidism may be associated with anemia in a Bahraini population was tested. Association of hyperparathyroidism and vitamin D levels (deficiency and insufficiency) with anemia was investigated in 421 Bahrainis (213 males and 208 females). In females, the prevalence of anemia was significantly associated with vitamin D deficiency independent of parathyroid hormone levels (odds ratio: 2.9; 95% confidence interval: 2.3-10.5; P = 0.001). In females, the prevalence of anemia appeared to be significantly associated with hyperparathyroidism (odds ratio: 2.1; 95% confidence interval: 1.2-3.7; P = 0.01); however, this significant association disappeared when adjusted for vitamin D deficiency (odds ratio: 1.6; 95% confidence interval: 0.75-6.5; P = 0.154). Results from this study suggest that vitamin D deficiency is independently associated with anemia in females but not males. Further studies to determine whether vitamin D supplementation could be used to treat anemia are warranted.

High glucose-induced oxidative stress increases the copy number of mitochondrial DNA in human mesangial cells.

Oxidative damage to mitochondrial DNA (mtDNA) has been linked to the pathogenicity of diabetic nephropathy. We tested the hypothesis that mtDNA copy number may be increased in human mesangial cells in response to high glucose-induced reactive oxygen species (ROS) to compensate for damaged mtDNA. The effect of manganese superoxide dismutase mimetic (MnTBAP) on glucose-induced mtDNA copy number was also examined. The copy number of mtDNA was determined by real-time PCR in human mesangial cells cultured in 5 mM glucose, 25 mM glucose, and mannitol (osmotic control), as well as in cells cultured in 25 mM glucose in the presence and absence of 200 µ M MnTBAP. Intracellular ROS was assessed by confocal microscopy and flow cytometry in human mesangial cells. The copy number of mtDNA was significantly increased when human mesangial cells were incubated with 25 mM glucose compared to 5 mM glucose and mannitol. In addition, 25 mM glucose rapidly generated ROS in the cells, which was not detected in 5 mM glucose. Furthermore, mtDNA copy number was significantly decreased and maintained to normal following treatment of cells with 25 mM glucose and MnTBAP compared to 25 mM glucose alone. Inclusion of MnTBAP during 25 mM glucose incubation inhibited mitochondrial superoxide in human mesangial cells. Increased mtDNA copy number in human mesangial cells by high glucose could contribute to increased mitochondrial superoxide, and prevention of mtDNA copy number could have potential in retarding the development of diabetic nephropathy.

Sensitive and specific markers for insulin resistance, hyperandrogenemia, and inappropriate gonadotrophin secretion in women with polycystic ovary syndrome: a case-control study from Bahrain.

BACKGROUND: In women with polycystic ovary syndrome (PCOS), despite a high prevalence of insulin resistance, hyperandrogenemia, and disturbances in the secretion of gonadotrophin, the principal causes of biochemical abnormalities and the best endocrine markers for PCOS have not been fully identified. SUBJECTS AND METHODS: Serum levels of insulin, glucose, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, estrogen, sex hormone-binding capacity (SHBG), and other related indices such as homeostasis model assessment, insulin glucose ratios, LH/FSH ratios, and the free androgen index (FAI) were determined and compared in women with PCOS (n = 50) and women without PCOS (n = 50). RESULTS: In multivariate logistic regression analyses, among all insulin resistance indices, only hyperinsulinemia (odds ratio [OR] = 2.6; confidence interval [CI]: 1.3-5.2; P = 0.008) was significantly and independently associated with PCOS when adjusted for body mass index (BMI), hyperandrogenemia, and LH/FSH ratios. The LH/FSH ratio (OR = 5.4; CI: 1.2-23.0, P = 0.03) was the only marker among those indices for inappropriate gonadotrophin secretion that significantly and independently associated with PCOS when adjusted for BMI and hyperinsulinemia. Among those indices for hyperandrogenemia, FAI (OR = 1.1; CI: 1.0-2.7; P = 0.02) and SHBG (OR = 1.2; CI: 1.2-3.4; P = 0.03) were significantly and independently associated with PCOS when adjusted for BMI and hyperinsulinemia. In addition, receiver operating characteristic analysis showed that the best predictive markers for PCOS were insulin (area under the curve [AUC] = 0.944; CI: 0.887-0.989), FAI (AUC = 0.932; CI: 0.895-0.993), SHBG (AUC = 0.924; CI: 0.87-0.978), and LH/FSH ratios (AUC = 0.906; CI: 0.821-0.965). CONCLUSION: For insulin and LH/FSH ratios, FAI, and SHBG seemed the best predictors and markers for insulin resistance, inappropriate gonadotrophin secretion, and hyperandrogenemia, respectively, with high sensitivity and specificity for identifying Bahraini women with and without PCOS.

Association between low red blood cell 5-methyltetrahydrofolate and hyperhomocysteinaemia with hypertension : a cross-sectional study.

BACKGROUND: Hyperhomocysteinaemia and other risk factors associated with blood pressure have been reported in large community-based studies in different populations. However, it is not fully established whether hypertension is associated with high plasma total homocysteine levels (tHcy) or components of the homocysteine re-methylation pathway including vitamin B(12), plasma 5-methyltetrahydrofolate (5-MTHF) or red blood cell (RBC) 5-MTHF. AIM: In this study we tested the hypothesis that RBC 5-MTHF could be a marker for long-term folate status in the blood and low RBC 5-MTHF may be associated with hypertension. METHODS: This was a cross-sectional study in a community-based setting and 492 males and 431 females were investigated. Systolic and diastolic blood pressures were determined and fasting blood samples were taken for determination of plasma tHcy, creatinine, uric acid, lipids, plasma 5-MTHF, RBC 5-MTHF and vitamin B(12). RESULTS: In males, the risk of hypertension was significantly (95% CI 1.9, 8.7; p = 0.003) increased by 1.8-fold in the first quartile compared with the highest quartile of RBC 5-MTHF when adjusted for body mass index (BMI), age, dyslipidaemia, uric acid, creatinine, smoking, plasma tHcy and vitamin B(12). The risk of hypertension was also significantly increased (95% CI 1.1, 9.2; p = 0.03) by 1.1-fold in the highest quartile compared with the lowest quartile of plasma tHcy when adjusted for BMI, age, dyslipidaemia, uric acid, creatinine, smoking, plasma and RBC 5-MTHF and vitamin B(12). There were no associations of hypertension with plasma tHcy, and other components of the Hcy re-methylation pathway were observed in females. CONCLUSIONS: The association between hypertension and low RBC 5-MTHF was stronger than any other components of the homocysteine re-methylation pathway. Results from this study suggest that folate measurements in RBC seem to be the most reliable marker indicating 5-MTHF deficiency and disturbances in the Hcy re-methylation pathway in association with hypertension.

Leptin-to-adiponectin, adiponectin-to-leptin ratios, and insulin are specific and sensitive markers associated with polycystic ovary syndrome: a case-control study from Bahrain.

OBJECTIVE: Hyperinsulinemia and adipokines such as leptin and adiponectin with respective proatherogenic and antiatherogenic properties are reported to be the major contributors to pathogenesis of polycystic ovary syndrome (PCOS), including to the development of type 2 diabetes and coronary artery disease. In this study, the association of hyperinsulinemia, hyperleptinemia, hypoadiponectinemia, high leptin-to-adiponectin (L/A) and adiponectin-to-leptin (A/L) ratios as risk factors associated with PCOS in Bahraini women was investigated. PARTICIPANTS AND METHODS: Serum levels of insulin, leptin, adiponectin, cholesterol, triglyceride, A/L and L/A ratios were compared in women with PCOS and controls to investigate tentative and potential diagnostic markers for women with PCOS. RESULTS: Insulin was significantly higher in PCOS cases than controls (15.0±3.0 vs. 6.5±1.72, P<0.001). Leptin was significantly higher in PCOS cases than in controls (39.9±4.6 vs. 26.4±3.4, P<0.001), whereas adiponectin was significantly lower in PCOS cases than in controls (8.7±3.0 vs. 11.1±3.6, P<0.001). In addition, L/A ratios were significantly higher in PCOS cases than in controls (4.8±2.7 vs. 2.3±1.6, P<0.001), whereas A/L ratios were significantly lower in PCOS cases than in controls (0.25±0.08 vs. 0.50±0.1, P<0.001). In multivariate logistic regression analyses, insulin [odds ratio (OR)=2.1, confidence interval (CI) 1.2-3.8, P=0.01], A/L (OR=1.6, CI 1.4-7.2, P=0.03), and L/A (OR=1.4, CI 1.2-2.0, P=0.04) were independently associated with PCOS. Receiver operating characteristic analyses showed that the best predictive markers for PCOS were insulin [area under the curve (AUC)=0.937, CI 0.887-0.989] L/A and A/L ratios (AUC=0.861, CI 0.786-0.936), indicating their high sensitivity and specificity for diagnosis of PCOS. CONCLUSION: In Bahraini women with PCOS, insulin, L/A, and A/L ratios seem to be the best markers to distinguish women with and without PCOS.

Neonatal screening for congenital hypothyroidism: a retrospective hospital based study from Bahrain.

BACKGROUND: Neonatal screening programs for congenital hypothyroidism (CH) are now widespread in developed countries. AIM: Cord blood thyroid-stimulating hormone (TSH) was evaluated for the incidence of CH in Bahrain Defense Force hospital. METHODS: Those neonates with cord blood TSH values >25 mU/l were recalled. Permanent CH was reported when the levels of TSH and free T4 (fT4) venous blood samples were > or =15 mUl and <12 pmol/l, respectively, with abnormal thyroid scan. RESULTS: Of 714 recalled newborns, 23 (10 males and 13 females) were diagnosed with transient TSH elevation with an estimated incidence of 1:774 births and 6 (3 males and 3 females) were diagnosed with permanent CH with an overall estimated incidence of 1:2,967 births. CONCLUSIONS: High incidence rates for CH reported in this hospital-based study suggest the need for a national screening program for this congenital endocrine disorder in the Kingdom of Bahrain.

Efficacy of fine-needle aspiration biopsy in diagnosis of breast cancer: a retrospective study of 303 cases in Bahrain.

Breast cancer is a leading cause of death in many countries worldwide and breast lesions remain a common diagnostic dilemma. Fine-needle aspiration biopsy (FNAB) has been suggested as the most important, first line, minimally invasive measure in the management of patients with breast lesions. The aim of this study is to evaluate the efficacy of FNAB in patients with breast lesions by comparing the diagnostic accuracy of cytology results with that of the definitive histological examination outcome and also to investigate the added value of a single aspirator experience to the overall diagnostic precision and compared with the internationally published results. A retrospective study of 303 breast FNAB samples were carried out by a single experienced cytopathologist with complete comparison records.The prevalence of positive cytologic diagnosis for the breast cancer was determined to be 20.4%. The overall diagnostic accuracy of FNAB was 97.9%, with a specificity and sensitivity of 98.3 and 96.5%, respectively. The overall positive and negative predictive values were determined to be 93.2 and 99.2%, respectively. In addition, the sensitivity was comparable in cases that have been attempted by palpation-guided sampling compared with those aspirations that were carried out under US guidance.Results from this study confirm that FNAB biopsies performed and reported by a dedicated, single, skilled cytopathologist are highly effective in diagnosis of breast lesions and reliable in differentiating benign and malignant breast lesions with an overall high efficacy in a specialized laboratory-based FNAB clinic.

Hyperhomocysteinemia induces insulin resistance in male Sprague-Dawley rats.

Association between elevated plasma homocysteine levels and insulin resistance has been reported, however, whether hyperhomocysteinemia induces insulin resistance or it is actually hyperinsulinemia that causes elevated plasma homocysteine levels, the direction of causality in this association is not still clear. In this study, we examined the hypothesis that hyperhomocysteinemia may cause hyperinsulinemia leading to insulin resistance in rats. Plasma glucose, insulin and total homocysteine concentrations were determined in two groups of male Sprague-Dawley rats, a test group that administered with homocysteine and a control group with no homocysteine in daily drinking water before and after 50 days. Oral glucose tolerance tests were also performed in control and test groups before and after 50 days. Mean fasting plasma insulin level was significantly higher (42.5+/-20.4 mU/L versus 23.2+/-5.9 mU/L, p=0.01), whereas mean glucose: insulin ratio was significantly lower in test rats than in control rats (0.12+/-0.07 versus 0.17+/-0.05, p=0.04) after 50 days. In addition, mean homeostasis assessment insulin resistance index was significantly higher in test rats than in control rats (7.5+/-3.5 versus 4.0+/-1.6, p=0.02) after 50 days. The mean plasma glucose level was not significantly different (4.1+/-1.1 mmol/L versus 3.9+/-0.8 mmol/L, p=0.57) between controls and test rats, however, the results from oral glucose tolerance tests showed the development of insulin resistance in test rats after 50 days administration of homocysteine. Results from this in vivo study suggest that homocysteine can cause insulin resistance and this relationship may need to be considered when evaluating the role of plasma homocysteine as a risk factor in patients with obesity and type II diabetes.

Association of methylenetetrahydrofolate reductase (C677T) polymorphism with hyperuricemia.

BACKGROUND AND AIMS: Homozygosity for the thermolabile variant of 5,10-methylene tetrahydrofolate reductase (C677T) has been suggested to be positively associated with the risk of vascular disease and neural tube defects. In addition, recent studies have suggested that elevated serum uric acid predicts ischemic heart disease, and epidemiological data on ethnic groups have suggested that genetic factors are determinants of serum uric acid levels. In this study, we tested the hypothesis that 5,10-methylenetetrahydrofolate reductase (C677T) polymorphism may be associated with hyperuricemia. METHODS AND RESULTS: Samples from 518 healthy individuals (268 men and 250 women) were analyzed for MTHFR genotyping and serum uric acid. The participants were categorized to homozygous wild type (CC), heterozygous for wild type and thermolabile (CT), or homozygous for the thermolabile (TT) variant. Serum uric acid was significantly higher in males and females with TT genotype than those with either CC or CT genotype (p=0.0001, ANOVA). Univariate and multivariate analysis showed that 5,10-methylenetetrahydrofolate reductase (C677T) polymorphism was a strong correlate and predictor of uric acid in males (r=0.28, p=0.0001, beta=0.673, p=<0.001) and in females (r=0.27, p=0.0001, beta=0.599, p=<0.001). Odds ratio analysis has also shown that the risk of hyperuricemia was greater in males (OR 3.1, CI 1.8-5.2, p=0.001) and females (OR 3.3, CI 1.9-5.7, p=<0.001) with CT genotypes and in males (OR 3.7, CI 1.3-10.7, p=0.014) and females (OR 3.2, CI 1.1-9.7, p=0.032) with TT genotypes than in those with CC genotypes. CONCLUSION: Results from this study suggest that mutation of 5-MTHFR C677T contributes to the higher uric acid levels in both males and females and may be a risk factor for hyperuricemia.

The angiotensin type 1 receptor antagonist valsartan attenuates pathological ventricular hypertrophy induced by hyperhomocysteinemia in rats.

INTRODUCTION: Clinical and experimental studies have reported the role of homocysteine in ventricular hypertrophy. Activation of the renin-angiotensin system mediated by angiotensin II type 1 (AT1) receptor has also been suggested to contribute to the pathogenesis of ventricular hypertrophy. There are also reports suggesting the affect of angiotensin II (Ang II) on cardiac hypertrophy is mediated by hyperhomocysteinemia. However, there is limited information on the mechanisms of the possible relationship between homocysteine and Ang II in ventricular hypertrophy. In this study we tested the hypothesis that hyperhomocysteinemia induced ventricular hypertrophy and remodelling may be mediated through activation of Ang II AT1-receptors in rats. METHODS: This study was conducted on control non-treated rats (n=13), methionine-treated rats (1.5 mg/kg/day, n=18) and methionine plus oral AT1 antagonist (valsartan, 30 mg/kg/day, n=13) treated rats for 56 days. Systolic blood pressure (SBP) was determined in rats at baseline, 28 and 56 days. Echocardiography was also performed in all rats after eight weeks, and blood samples were obtained for determination of plasma tHcy. Rats were then sacrificed for histopathological and biochemical assessment of cardiac structure. RESULTS: The SBP in the methionine-treated rats was significantly higher compared with controls and significantly lower compared with the methionine-valsartan group at 28 and 56 days (p<0.001). In addition, left ventricular wall thickness (LVWT) in the methionine-valsartan group (4.36+0.11 mm) was significantly lower compared with the methionine group (5.0+0.23 mm, p=0.03). Furthermore, cardiac collagen to total protein ratio was significantly lower in the methionine-valsartan group (2.19+0.11%) compared with the methionine group (2.64+0.08%, p=0.026). Fractional shortening (FS) was not significantly different between groups. CONCLUSION: Results from this study suggest that hyperhomocysteinemia-induced hypertension and ventricular hypertrophy in rats are mediated, at least partly; by Ang II activation of AT1-receptors.

Chronic administration of nandrolone decanoate does not increase the plasma homocysteine level of male rats.

Androgenic-anabolic steroids are used widely by many athletes in order to increase muscle mass and strength. Since plasma total homocysteine, an independent risk factor of vascular diseases, is higher in men than in women, it has been proposed that androgenic hormones could increase the plasma total homocysteine level and it might play some role in sudden death when used at supraphysiological doses. To study the association between the use of androgenic-anabolic steroids and plasma homocysteine level, nandrolone decanoate was administered in 3 and 10 mg/kg doses to male rats by intramuscular weekly injections. Control animals received the solvent of nandrolone decanoate. After 14 weeks, plasma total homocysteine level was measured. In order to make sure about the adequacy of doses and bioavailability of drug, testes parameters were also considered. While all testes parameters were suppressed significantly, no association between androgenic-anabolic steroids use and total homocysteine level was found. It is concluded that chronic administration of nandrolone decanoate does not have any significant effect on plasma total homocysteine of male rats. Thus, factors other than plasma total homocysteine level may contribute to increased cardiovascular events after chronic abuse of androgenic-anabolic steroids.

Association of red blood cell 5-methyltetrahydrofolate and severity of coronary artery disease: a cross-sectional study from Shiraz, southern Iran.

In this study we tested the hypothesis that red blood cell 5-methyltetrahydrofolate, a long-term marker of the folate status, is associated with the severity of coronary artery disease and whether this association is independent of homocysteine, vitamin B12, plasma 5-methyltetrahydrofolate, 5,10-methyltetrahyrofolate reductase C677T genotype, and other cardiovascular risk factors. Two hundred and fifty-one angiographically documented patients aged <70 years with single, double, or triple coronary artery disease were investigated. Red blood cell 5-methyltetrahydrofolate concentrations were significantly decreased with the increasing number of diseased vessels (analysis of variance, P < 0.001). Red blood cell 5-methyltetrahydrofolate was also inversely and significantly correlated with the number of diseased vessels (r = -0.36, P < 0.001). Stepwise multiple regression analysis showed that red cell 5-methyltetrahydrofolate was a strong predictor of number of diseased vessels independent of plasma total homocysteine, 5,10-methyltetrahyrofolate reductase C677T genotype, and all other coronary artery risk factors (beta = -0.002, P < 0.001, r2 = 0.128). The results of this study suggest that low red blood cell 5-methyltetrahydrofolate is associated with the severity of coronary artery disease independent from plasma homocysteine and other cardiovascular risk factors.

Association of low red blood cell folate concentrations with coronary artery disease in Iranians: a matched case-control study.

BACKGROUND: It is not fully established whether the increasing risk of coronary artery disease (CAD) is associated with high plasma homocysteine levels or components of the homocysteine remethylation pathway, e.g. vitamin B(12) or 5-methyltetrahydrofolate (5-MTHF) in plasma and red blood cells (RBC). In this study, we tested the hypothesis that 5-MTHF in RBC, which represents the long-term folate status of individuals, may be a more reliable marker of homocysteine remethylation pathway disturbances, and its deficiency may be associated with CAD in Iranians. METHODS: Plasma total homocysteine (tHcy), vitamin B(12), and plasma and RBC 5-MTHF were measured in 200 angiographically documented patients and 200 controls matched for sex and age. RESULTS: In the plasma, tHcy levels were significantly higher in cases compared to controls (geometric mean 12.9 +/- 6.5 vs. 10.6 +/- 5.6 micromol/l, p = 0.04). However, RBC 5-MTHF (527.2 +/- 185.9 vs. 461.3 +/- 117.9 nmol/l, p = 0.007) and vitamin B(12) (254.2 +/- 132.8 vs. 182.2 +/- 110.4 pmol/l, p = 0.04) were significantly higher in controls than patients. RBC 5-MTHF was a strong and independent predictor of plasma tHcy (beta = -0.01, p = 0.003, r(2) = 0.19). Subjects in the lowest quartile of red-cell 5-MTHF had a 2.5-fold increased prevalence of CAD compared to subjects in the highest quartile. The association of CAD in the first quartile with red-cell 5-MTHF remained significant when adjusted for plasma tHcy, vitamin B(12), hypertension and hypercholesterolemia (odds ratio, OR 2.3, confidence interval: 1.1-3.9, p = 0.01). However, the association between CAD in the highest quartile and plasma tHcy decreased and became insignificant when adjusted for red-cell 5-MTHF, vitamin B(12), hypertension and hypercholesterolemia (OR 1.27, confidence interval: 0.96-1.69, p = 0.11). CONCLUSION: In this study, the association between CAD and low RBC 5-MTHF was stronger than with plasma 5-MTHF and plasma tHcy levels, indicating that RBC 5-MTHF may be a more stable parameter to study disturbances in the homocysteine remethylation pathway in Iranians.

Association of plasma folate, plasma total homocysteine, but not methylenetetrahydrofolate reductase C667T polymorphism, with bone mineral density in postmenopausal Iranian women: a cross-sectional study.

Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) have been well documented to cause hyperhomocysteinemia, and recent studies suggest an association of C677T mutation of methylenetetrahydrofolate reductase with low bone mineral density (BMD). In this study, the association of plasma total homocysteine (Hcy), plasma folate, and vitamin B12 as well as methylenetetrahydrofolate reductase C667T polymorphism with bone mineral density at neck of femur and lumbar spine in 271 postmenopausal Iranian women was investigated. Bone mineral density was measured by dual-energy X-ray absorptiometry. Restriction fragment length polymorphism was used for genotyping the methylenetetrahydrofolate reductase polymorphism. Plasma total homocysteine, plasma folate, and vitamin B12 were also determined. The bone mineral densities at the neck of femur and lumbar spine together with other clinical characteristics among methylenetetrahydrofolate reductase genotypes (CC, CT, and TT) were examined. Bone mineral densities at both neck of femur (r = -0.18, P = 0.003) and lumbar spine (r = -0.16, P = 0.01) were significantly and negatively correlated with the logarithm of plasma total homocysteine. Bone mineral density at the lumbar spine was also significantly and positively associated with plasma folate (r = 0.14, P = 0.02). However, no correlation between methylenetetrahydrofolate reductase polymorphism with bone mineral density at neck of femur (r = -0.01, P = 0.81) and lumbar spine (r = -0.04, P = 0.51) was observed. The negative association of plasma total homocysteine with bone mineral density was no longer significant when adjusted for folate and vitamin B12. Plasma folate and age were the main predictors of plasma total homocysteine explaining 15.3% and 5.2% of the variance of plasma total homocysteine, respectively. Methylenetetrahydrofolate reductase polymorphism, however, was not associated with plasma folate (r = 0.086, P = 0.17) or vitamin B12 (r = 0.05, P = 0.4). Plasma folate was one of the main predictors explaining 3.0% and 1.7% of variance of the bone mineral density at femoral neck and lumbar spine, respectively. Results from this study suggest hyperhomocysteinemia as a result of folate deficiency, but not methylenetetrahydrofolate reductase polymorphism, is independently associated with low bone mineral density and may contribute to the pathogenicity of osteoporosis in postmenopausal Iranian women.

Distribution of plasma total homocysteine concentrations in the healthy Iranians.

OBJECTIVE: The distribution of plasma total homocysteine concentrations in a population of South West of Iran Shiraz is described to test for differences in homocysteine concentrations among gender and age groups and those levels reported in other populations. DESIGN AND METHODS: Two hundred one healthy males and 201 healthy females aged >15 years from Shiraz, Iran, were randomly selected. Plasma total homocysteine concentrations were measured using high-performance liquid chromatography. RESULTS: The mean plasma homocysteine level was significantly higher in men (geometric mean, 7.3 micromol/l) than in women (geometric mean, 6.3 micromol/l, P < 0.001). The geometric mean levels for ages 15-25, 26-36, 37-47, and 48-58, 59-69, and 70-80 years, were 5.9, 5.4, 5.2, 6.7, 7.3, and 7.6 micromol/l in women and 7.5, 8.7, 5.9, 5.9,7.2, and 9.1 micromol/l in men, respectively. CONCLUSIONS: The homocysteine distribution in a representative sample of people of southwest of Iran indicates age and gender differences, as is found in other populations.