Distribution of 5,10-methylenetetrahydrofolate reductase (C667T) polymorphism and its association with red blood cell 5-methyltetrahydrofolate in the healthy Iranians

BACKGROUND AND AIMS: Homozygosity for the thermolabile variant of 5,10-methylenetetrahydrofolate reductase (C677T) that causes hyperhomocysteinemia has been reported in 5-15% of general populations. This mutation has also been suggested to be positively associated with the risk of vascular disease and neural tube defects. It has also been suggested that present dietary reference values may need to be altered for people heterozygote or homozygote for this mutation as tissue folate status has been reported to be compromised by these genetic variants. The aims of this study were to investigate the distribution of 5,10-methylenetetrahydrofolate reductase (C677T) polymorphism in a population of Shiraz, south west of Iran and to test the hypothesis that folate status is compromised by this mutation in our population. METHODS: In this study age, body mass index, plasma and red blood cell 5-methytetrahydrofolate, plasma total homocysteine and vitamin B12 of 391 healthy Iranians (198 men and 193 women) together with methylenetetrahydrofolate reductase C667T genotypes were determined. The correlates of methylenetetrahydrofolate reductase polymorphism were determined using univariate and multivariate statistical analysis. RESULTS: The frequencies of CC, CT and TT genotypes were 56.2%, 38.7% and 5.1%, respectively. The C and T allele frequencies were determined to be 0.76 and 0.24, respectively and this polymorphism was compatible with Hardy-Weinberg equilibrium (X2=1.54, df=2, P=0.46). Among all the variables examined, red blood cell 5-methyltetrahydrofolate (P=0.007, ANOVA) and plasma 5-methyltetrahydrofolate (P=0.012, ANOVA) were significantly lower in individuals with TT genotype than those with either CC or CT genotype. Plasma total homocysteine was significantly higher in individuals with TT than those with either CC or CT genotype at below the median levels of red blood cell 5-methylterahydrofolate (P=0.03, ANOVA) and plasma 5-methylterahydrofolate (P=0.04, ANOVA). Univariate (r=-0.16, P=0.002) and multivariate analysis (beta=-0.0005, P=0.003) showed that red blood cell 5-methylterahydrofolate was the strongest correlates of methylenetetrahydrofolate reductase genotypes. CONCLUSIONS: Results from this study suggest that methyltetrahydrofoate reductase C667T genotypes are strongly and independently associated with low red blood cell 5-methylterahydrofolate that has been reported to be a more reliable and long-term marker for body's folate status among Iranians. These results may suggest that substantial minority of people in general populations may have increased folate needs and this may place doubts on the validity of assuming "normality" for nutrient requirements in any general population.     

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. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Association of red blood cell 5-methyltetrahydrfoate folate with bone mineral density in postmenopausal Iranian women

Recent studies have suggested that hyperhomocystenemia and low plasma folate are associated with fracture and also bone mineral density (BMD) and that they may contribute to the pathogenicity of osteoporosis in postmenopausal women. However, as plasma total homocysteine (tHcy) and plasma folate can be regarded as short-term markers when compared to a long-term variable such as BMD, in this study we tested the hypothesis that low red blood cell 5-methyltetrahydrofolate (RBC 5-MTHFR) as a long-term marker of the folate status may be a better predictor of BMD than plasma 5-MTHF, and its deficiency may contribute to the pathogenecity of osteoporosis in postmenopausal Iranian women. The BMD at the femoral neck and lumbar spine (measured by dual-energy X-ray absorptiometry, DXA) together with anthropometric and biochemical components of the homocysteine re-methylation pathway including plasma tHcy, 5-MTHF and vitamin B12, RBC 5-MTHF and creatinine were determined in 366 postmenopausal women. RBC 5-MTHF was more highly correlated with BMD at the lumbar spine ( r =0.21, P =0.001) and femoral neck ( r =0.19, P =0.004) than was plasma 5-MTHF (lumbar spine; r =0.14, P =0.03 and femoral neck; r =0.17, P =0.006). Stepwise multiple linear regression analyses revealed that RBC 5-MTHF was one of the predictors of BMD explaining 4.3 and 4.0% variance of BMD at the lumbar spine and femoral neck, respectively, whereas plasma 5-MTHF was excluded in the model and not determined to be a predictor of BMD at both the lumbar spine and femoral neck when adjusted for age, BMI, years since menopause and RBC 5-MTHF. This study suggests that RBC 5-MTHF is a better predictor of BMD than plasma 5-MTHFR when compared to a long-term marker such as BMD, and its deficiency is associated with low BMD that may contribute to the pathogenecity of osteoporosis in postmenopausal women.     

Association of methylenetetrahydrofolate reductase (C677T) polymorphism with hyperuricemia

Background and aimsHomozygosity 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 resultsSamples 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, β = 0.673, p = <0.001) and in females (r = 0.27, p = 0.0001, β = 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.ConclusionResults 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.     

Selective screening of amino acid disorders in the south-west of Iran,Shiraz

A diagnostic study of amino acid concentrations in dried blood spot samples from 1044 symptomatic children revealed high incidences of phenylketonuria, tyrosinaemias, and maple syrup urine disease in the Shiraz region of Iran. Minimum incidences, based on babies born between 1996 and 2001 inclusive, and diagnosed by the end of 2001, are 1:3672, 1:10651 and 1:21303, respectively.     

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 (β = −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.     

Contribution of endogenous opioids and nitric oxide to papillary muscle contractile impairment in cholestatic rats

Attenuated responsiveness to adrenoceptor stimulation has been proposed as an important factor underlying cardiovascular complications of cholestasis. We examined isolated papillary muscle responsiveness to alpha (phenylephrine) and beta-adrenoceptor (isoproterenol) agonists in 7-day bile duct-ligated rats. We investigated the role of nitric oxide (NO) and endogenous opioids in papillary muscle hyporesponsiveness to isoproterenol stimulation. In order to evaluate the effect of NO and endogenous opioids, animals were treated with chronic subcutaneous injections of N(omega)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg/day) or naltrexone (20 mg/kg/day), or isolated papillary muscles were exposed acutely to the same drugs (10(-4) and 10(-6) M, respectively) in an organ bath. The basal contractile force of papillary muscle, +dT/dtmax and -dT/dtmax, was significantly decreased in bile duct-ligated rats compared to sham-operated ones (P<0.05, for each value). The concentration-response curve for phenylephrine and isoproterenol demonstrated a reduced maximum effect in bile duct-ligated rats compared to the sham-operated group (P<0.01 and 0.05, respectively). Basal contractile abnormalities of bile duct-ligated rats were corrected by L-NAME or naltrexone treatment, either acute or chronic. While chronic L-NAME treatment resulted in a left-ward shift (P<0.05), it had no effect on the maximum effect in bile duct-ligated rats. Acute L-NAME treatment did not influence isoproterenol responsiveness. Acute and chronic naltrexone treatment resulted in partial and complete correction of the hyporesponsiveness of bile duct-ligated rats, respectively (P<0.05). This investigation demonstrates that the papillary muscles of 7-day bile duct ligated-rats have an impaired basal contractility and hyporesponsiveness to both alpha and beta-adrenoceptor stimulation. It also provides evidence for the involvement of increased opioidergic tone and NO overproduction in cholestasis-induced cardiac impairment.     

Prenatal Magnetic Resonance Imaging (MRI) Findings of a Foregut Duplication Cyst of the Tongue

Foregut duplication cysts of the oral cavity or lingual choristomas have a potential risk of airway obstruction. Two cases are reported that were initially detected by screening sonography. Further imaging with both static and real‐time cine magnetic resonance imaging confirmed the lingual origin, relationship of the mass to fluid‐filled spaces within the oral cavity, motion of the mass with the tongue during fetal swallowing, and airway patency. The additional information provided by magnetic resonance imaging aided in planning delivery and obviated the need for an ex utero intrapartum treatment procedure because airway patency was confirmed in both cases.