Influence of the TAS2R38 Gene Single Nucleotide Polymorphisms in Metabolism and Anthropometry in Thyroid Dysfunction.

The gene TAS2R38 single nucleotide polymorphisms (SNPs-P49A, A262V and V296I) can condition bitter tasting by PAV (proline-alanine-valine) and non-bitter-tasting by AVI (alanine-valine-isoleucine) homozygosity. We evaluated this polymorphisms association with thyroid function, metabolism and anthropometry parameters determined by: Endpoint analysis (SNPs); DXA (fat mass-%, total fat mass-kg, lean mass-kg); Standard methods (lipid metabolism parameters, HbA1c-%, glycemia-mg/dL, insulinemia-µIU/mL, HOMA-IR, uricemia-mg/dL, calcemia-mg/dL and BMI-kg/m2); ELISA (leptinemia-ng/mL); Spectrophotometry (Angiotensin Converting Enzyme activity-UI/L). Statistics: SPSS program; OR [IC95%]; p < 0.05. Sample: 114 hypothyroid, 49 hyperthyroid, and 179 controls. An association between A262V-valine-valine and hypothyroidism/hyperthyroidism was verified (OR = 2.841; IC95% [1.726-4.676]), p < 0.001/OR = 8.915; IC95% [4.286-18.543]), p < 0.001). Protector effect from thyroid dysfunction: A262V-alanine-valine (OR = 0.467; IC95% [0.289-0.757], p = 0.002/OR = 0.132; IC95% [0.056-0.309], p < 0.001) and PAV (OR = 0.456; IC95% [0.282-0.737], p = 0.001/OR = 0.101; IC95% [0.041-0.250], p < 0.001). Higher parameter values associated with genotypes were: fat-mass-% (V296I-valine-isoleucine), lean-mass (P49A-proline-proline; PVI), leptin (AVI), HbA1c (A262V-alanine-valine) and lower values in lean-Mass (AVI; PVV), leptin (A262V-alanine-alanine), HbA1c (PVV), uricemia (V296I-valine-isoleucine), glycemia (A262V-alanine-alanine; AAV) and plasma triglycerides (PVV). In conclusion, TAS2R38 influences thyroid function, body composition and metabolism. Bitter taste perception (PAV) and the genotype A262V-alanine-valine can protect from thyroid dysfunction. AVV, PVV and genotype A262V-valine-valine may confer higher predisposition for thyroid dysfunction, particularly PVV for hyperthyroidism.

Nutritional counselling in adults promoting adherence to the Mediterranean diet as adjuvant in the treatment of major depressive disorder (INDEPT): a randomized open controlled trial study protocol.

BACKGROUND: Major Depressive Disorder (MDD) is a leading cause of disability worldwide. Approximately one-third of patients with MDD do not respond to treatment, and often exhibit elevated inflammation biomarkers, which are associated with worse prognosis. Previous research has linked healthier dietary patterns, such as the Mediterranean Diet (MedDiet), with a lower risk of MDD and symptoms of depression, potentially due to their anti-inflammatory properties. The aim of this study is to evaluate the effectiveness of a nutritional counselling intervention promoting MedDiet to alleviate symptoms of depression in adults recently diagnosed with MDD and presenting with elevated inflammation biomarkers. METHODS: This study is a randomized controlled trial (RCT) that will recruit adults from outpatient clinics, between the ages of 18 and 70 years who have been diagnosed with MDD and are currently receiving treatment with the first prescribed antidepressant, and who exhibit elevated inflammation biomarkers (interleukin-6 and/or C-reactive protein). The control group will receive treatment-as-usual (TAU) only. The primary outcome of the study will be the change in symptoms of depression, as measured by the Beck Depression Inventory 2 (BDI-II), after 12 weeks of intervention. Data analysis will follow an intention-to-treat approach. Secondary outcomes will include changes in inflammation biomarkers, quality of life, adherence to the MedDiet, and cost-effectiveness of nutritional counselling. All outcomes will be assessed at baseline, after the 12-week intervention, and at 6- and 12-months post-baseline. DISCUSSION: This study will be the first RCT to evaluate the effect of a nutritional intervention with anti-inflammatory properties, as an adjuvant in the treatment of MDD, in individuals diagnosed with MDD and elevated inflammation biomarkers. The results of this study may contribute to the development of more effective and personalized interventions for MDD patients with elevated inflammation biomarkers.

Association of myeloperoxidase polymorphism (G463A) with cervix cancer.

Cervical cancer is the fourth most common cancer affecting women worldwide, according to the latest IARC release with 528 000 new cases every year. Infection by high-risk human papillomavirus (HPV) is necessary but not sufficient for progression to cancer. Epithelial tissues, the target of HPV infection, are heavily exposed to reactive oxygen species (ROS). Hypochlorous acid (HOCl) is a very potent ROS, and it is produced by myeloperoxidase (MPO). MPO, a lysosomal enzyme expressed in polymorphonuclear neutrophils (PMN), has the potential to kill HPV transformed cells, as a component of an intercellular induced-apoptosis pathway. This enzyme catalyzes the production of HOCl in the presence of hydrogen peroxide (H2O2). The H2O2 produced by the Doderlein's bacillus will interact with MPO, contributing to the intercellular induced-apoptosis pathway. We studied a functional polymorphism in the promoter region of MPO (G463A) and how it may affect the risk of developing cervix cancer. A sample of 100 patients with invasive cervical cancer and 122 control women were genotyped for MPO polymorphism by PCR-RFLP method. The statistical method used was χ(2). We found that women with the GG genotype had lower risk for cervical cancer than the women who displayed the heterozygous genotype GA (OR = 0.546, 95 % CI = 0.315-0.939, p = 0.028, OR = 2.210, 95 % CI = 1.257-3.886, p = 0.008, respectively). The genotype that leads to a higher concentration of ROS (GG) presents itself as a protection factor in comparison to the homozygous genotype (AA). This can be explained by the interaction of HOCl and superoxide of transformed cells that will generate apoptosis-inducing hydroxyl radicals.

The role of CYBA (p22phox) and catalase genetic polymorphisms and their possible epistatic interaction in cervical cancer.

Human papillomavirus (HPV) infection is necessary but not a sufficient cause for the development of invasive cervical cancer (ICC). Epithelial tissues, target for HPV, are exposed to reactive oxygen species (ROS) associated with tumor initiation and progression. The NADPH oxidase (NOX) and catalase (CAT) are involved in hydrogen peroxide (H2O2) production and inactivation, respectively. P22phox is the NOX subunit encoded by the CYBA gene that has a functional polymorphism (C-242T). This protein is involved in the regulation of electron transfer to oxygen. CAT is a hemic enzyme that plays a role in regulating H2O2 concentration, with a functional polymorphism (C-262T) in its gene. We evaluated CYBA C-242T and CAT C262T genetic polymorphisms and their interaction in 132 women with ICC. We found that CYBA C-242T and CAT C262T genotype frequencies were significantly different between ICC and controls (χ (2) test, p = 0.017 and p = 0.009, respectively). Women with the C/T CYBA-242 genotype had a lower risk for ICC development (odds ratio (OR) = 0.515, 95% confidence interval (CI) 0.291-0.914, p = 0.023) whereas T/T CAT-262 genotype carriers present an increased risk for ICC (OR = 3.034, 95% CI 1.462-6.298, p = 0.003). Women with C/C genotype for CYBA and T/T genotype for CAT had an increased risk to develop ICC comparing with the interaction of the other possible genotypes of both genes (OR = 3.952, 95% CI 1.075-14.521, p = 0.032). The CYBA C-242T and CAT C-262T genetic polymorphisms and their epistatic interactions can be associated with ICC through mechanisms related with the role of ROS in cell proliferation and apoptosis.

PP004. The polymorphism C677T of methylenetetrahydrofolate reductase (MTHFR), may increase risk for future higher blood pressure in women with previous hypertension in pregnancy.

INTRODUCTION: The MTHFR is a key enzyme in the folate cycle involved in homocysteine remethylation. The T allele of MTHFR C677T polymorphism is associated with lower activity inhibiting the DNA methylation and protecting from oxidative stress. OBJECTIVES: To evaluate the MTHFR genotype-phenotype relationship during and after pregnancy comparing hypertensive with normotensive women. METHOD: A sample of 380 women with 32.54±6.478 years old, 181 normotensive (NT) and 199 hypertensive (HBP) being 70.3% above 34 weeks of gestation. A subgroup 63 women with history of preeclampsia were studied 3-6 years postpartum and compared with 59 controls. The MTHFR was evaluated by PCR-RFLP using DNA extracted from peripheral blood. Statistical analysis evaluated with appropriated tests. RESULTS: The distribution of genotypes of the MTHFR was different according to blood pressure (BP), it was observed that the TT genotype had lower frequency in HBP (p<0.001). In the subgroup CC+CT the MPO levels were higher in HBP as well as nitrites, leucocytes, neutrophils, Apo B, BMI, waist and ratio waist/hip compared with NT (p<0.001, p=0.04, p=0.042, p=0.035, p=0.03, p=0.022, p=0.026, respectively). There were differences between levels of BP systolic and diastolic between women previously HBP and NT of CC+CT compared with TT carriers (p<0.001). CONCLUSION: The MTHFR may modulate blood pressure (BP) and cardiovascular risk. TT genotype with increased expression of antioxidant enzymes, may be a protective factor for future hypertension and cardiovascular risk compared with women CC and CT genotypes with higher levels of circulating biomarkers of inflammation.

Decreased erythrocyte activity of methemoglobin and glutathione reductases may explain age-related high blood pressure.

OBJECTIVES: Erythrocytes may play an important role in regulating blood pressure as storage sites for nitric oxide (NO). The objective of this work was to determine whether factors related to variations in erythrocyte metabolism associated with NO bioavailability, such as the activity of two enzymes--methemoglobin reductase (MHbR) and glutathione reductase (GSHR)--may help explain age-related increased blood pressure. METHODS: The sample consisted of 468 individuals of both sexes, 237 hypertensive (HT) and 231 normotensive (NT), aged between 18 and 98 years (48.81 +/- 19.46). The activity of MHbR (micromol.g Hb-1.min-1) and of GSHR (micromol.g Hb-1.min-1) was determined in erythrocytes by spectrophotometry. The statistical methods used were the Mann-Whitney test, Spearman's correlation coefficient and binary logistic regression. RESULTS: In this population, age was a risk factor for hypertension (OR=1.055, 95% CI = 1.045-1.065, p < 0.001). There was a significant difference in erythrocyte activity of these enzymes between normotensive and hypertensive subjects, with lower values in hypertensives: MHbR-NT = 16.97 (3.82-34.63), HT = 16.26 (3.26-37.10), p = 0.012; and GSHR-NT=57.60 (21.59-96.58), HT = 39.26 (23.07-90.27), p < 0.001. Enzyme activity was inversely correlated with age (MHbR: r = -0.193, p < 0.001; GSHR: r = -0.757, p < 0.001). MHbR correlated directly with GSHR only in hypertensive patients (r = 0.343, p = 0.034), which was not observed in normotensives. CONCLUSIONS: Age was a risk factor for hypertension. The erythrocyte activity of glutathione and metahemoglobin reductases, essential for redox balance and nitric oxide bioavailability in erythrocytes, may contribute only partially to the increased prevalence of age-related hypertension, and other factors should be taken into consideration, such as nutrition and antihypertensive medication.

ACP1 genotype, glutathione reductase activity, and riboflavin uptake affect cardiovascular risk in the obese.

Erythrocyte acid phosphatase (ACP locus 1), also known as low-molecular-weight protein tyrosine phosphatase, has previously been associated to glycemia, dyslipidemia, and obesity. In this study, ACP1 genotype and activity were tested in 318 women aged 19 to 83 (mean, 51.74 +/- 13.44) years. ACP1 genotype was found to directly correlate to glutathione reductase activity (P < .001) and levels of low-density lipoprotein cholesterol (P = .038). Glutathione reductase activity was in turn found to correlate to a series of cardiovascular risk factors such as systolic arterial pressure (P < .001), total cholesterol levels (P = .018), and low-density lipoprotein cholesterol levels (P = .039). A possible protective effect of ACP1 genotype AA against these cardiovascular risk factors was observed in this study. Furthermore, this work hypothesizes that nutritional riboflavin uptake becomes more crucial as body mass index increases, to counteract oxidative stress and minimize cardiovascular risk. This might be especially true in ACP1 genotypes AC, BC, and CC, which might possibly show the least endogenous protection against oxidative stress.

Plant extracts with anti-inflammatory properties--a new approach for characterization of their bioactive compounds and establishment of structure-antioxidant activity relationships.

Geranium robertianum L. (Geraniacea) and Uncaria tomentosa (Willd.) DC. (Rubiaceae) plant extracts, frequently used in traditional medicine for treatment of inflammatory and cancer diseases, were studied to identify potential bioactive compounds that may justify their therapeutic use and their underlying mechanisms of action. Since some of the pharmacological properties of these plant extracts may be linked to their antioxidant potential, the antioxidant activity, in relation to free radical scavenging, was measured by the ABTS/HRP and DPPH() assays, presenting U. tomentosa the higher activity. The antioxidant activity was also evaluated by scavenging of HOCl, the major strong oxidant produced by neutrophils and a potent pro-inflammatory agent. U. tomentosa was found to be a better protector against HOCl, which may justify its effectiveness against inflammatory diseases. SPE/LC-DAD was used for separation/purification purposes and ESI-MS/MS for identification/characterization of the major non-volatile components, mainly flavonoids and phenolic acids. The ESI-MS/MS methodology proposed can be used as a model procedure for identification/characterization of unknowns without the prerequisite for standard compounds analysis. The ESI-MS/MS data obtained were consistent with the antioxidant activity results and structure-activity relationships for the compounds identified were discussed.

Activity of two enzymes associated with apoptosis and cell aging in arterial hypertension.

OBJECTIVE: To study the activity of two enzymes, transmembrane reductase (TMR) and cytosolic low molecular weight protein tyrosine phosphatase (ACP1), in arterial hypertension (HT) in a sample of adults aged over 50 years. METHODS: A sample of 153 adults, 77 with hypertension and 76 normotensive (NT), aged between 50 and 90 years (mean: 71.87 +/- 11.59), of both sexes, was studied. TMR (mmol/cell/h) and ACP1 (micromol/gHb/h) activity in red blood cells was determined by spectrophotometry. Statistical analysis was carried out using the Student's t test and Pearson's correlation. RESULTS: We observed a significant difference in TMR activity between normotensive and hypertensive subjects, with lower levels in the hypertensives (NT = 4.762 +/- 2.595; HT = 3.878 +/- 1.748), p = 0.01. ACP1 activity, although higher in hypertensive patients, did not differ significantly from normotensive subjects (p = 0.08) (NT = 242.827 +/- 97.618; HT = 309.561 +/- 150.738). No correlation was observed between the activity of the two enzymes in either the hypertensive or the normotensive group. CONCLUSIONS: The lower level of activity of transmembrane reductase in arterial hypertension may be implicated in cardiovascular aging processes, reinforced by greater cytosolic acid phosphatase activity, with repercussions on cell proliferation and energy metabolism, leading to atherosclerosis.

[Erythrocytic acid phosphatase genetic polymorphism and cardiovascular risk in health children and adolescents]. / Polimorfismo genético da Fosfatase Acida do eritrócito e risco cardiovascular em crianças e adolescentes saudáveis.

OBJECTIVE: To correlate, in a sample of healthy children and adolescents, the activity of the enzyme acid phosphatase (ACP) with its different genetic phenotypes and of these with some cardiovascular risk parameters such as body mass index (BMI), percentage of total fat mass (%TFM), trunk fat (TF), insulin resistance, and the arterial blood pressure (BP). DESIGN AND METHODS: The sample was composed of 173 healthy children and adolescents, 96 (55.5%) F and 77 (44.5%) M, with ages between 10 and 16 years (mean: 13.04 +/- 1.68). The ACP activity was determined through a spectrophotometric method and its phenotypes through isoelectric focusing electrophoresis. BMI (Kg/m2) and the BP were obtained by standardized methods. Glycemia determined by the glucose oxidase method and insulinemia by RIA method. Insulin resistance based on the homeostasis model assessment (HOMA) was calculated as: [fasting insulin (microU/ml) x fasting glucose (mmol/l)]: 22.5. The %TFM and TF were determined by dual energy x-ray absorptiometry (DXA). The statistical methods used were ANOVA, the Pearson correlation and the Student's test. RESULTS: The distribution of the phenotypes were the following--absolute versus relative frequencies: BB-74 (48.4%), AB-52 (34%), AA-16 (10.5%), BC-7 (4.6%), AC-3 (2%) and CC-1 (0.7%). ACP activities (mean: 321.04 +/- 84.56) were significantly different among the phenotypes (p < 0.001). The smallest activity was observed in the AA individuals, the highest in CC, followed by BC (247.17 +/- 66.52 and 767.30 and 362.44 +/- 91.56 respectively). Glycemia was higher in the AA individuals (4.61 +/- 0.37) compared to CC + BC (4.40 +/- 0.31) (p = 0.08). A direct correlation was verified between HOMA and BP, both diastolic (p = 0.013, r = 0.250) and systolic (p = 0.015, r = 0.246), as well as of these with BMI (mean: 20.57 +/- 3.24) and insulinemia (p = 0.016, r = 0.215; p = 0.004, r = 0.280 and p = 0.007, r = 0.240; p = 0.008, r = 0.261 respectively for diastolic and systolic BP). There were no significant difference of BMI between sexes, nor of this as well as of % TFM and TF among the different genetic phenotypes of ACP. CONCLUSIONS: The smallest enzymatic activity of ACP seems to be associated with the AA individuals, where a trend for higher glycemia was verified. BMI, HOMA and insulinemia, due to their significant direct relationship with diastolic and systolic BP in this sample of children and adolescents may warrant more future attention in the evaluation of cardiovascular risk. There were no significant differences of HOMA, BMI, %TFM, TF nor of BP among the different ACP genetic phenotypes.