Interaction Effects of FTO and MC4R Polymorphisms on Total Body Weight Loss, Post-Surgery Weight, and Post-Body Mass Index after Bariatric Surgery.

Bariatric surgery (BS) is considered the most effective intervention for patients with severe obesity and is used to maintain long-term weight loss and glycemic control. The aim of this study was to analyze the effects of genotypes and haplotypes of the fat mass and obesity-associated (FTO) and melanocortin 4 receptor (MC4R) genes on total body weight loss (TBWL), post-surgery weight, and post-BMI after bariatric surgery. We retrospectively selected 101 patients from Bajio High Specialty Regional Hospital, León Guanajuato, México, who underwent Roux-en-Y gastric bypass (RYGB) to determine their body mass index (BMI), blood pressure, biochemical characteristics, and comorbidities. Post-surgery, patients were referred for registered anthropometry and blood pressure. Glucose, lipid and hepatic profiles, and insulin, leptin, and ghrelin levels were measured, and rs9939609, rs9930506, and rs1421085 FTO and rs17782313 MC4R polymorphisms were genotyped. Six (4-8) years after BS, post-surgery weight was greater in carriers of the rs9939609 and rs1421085 risk genotypes. TBWL was lower for the rs9930506 and rs1421085 risk genotypes. Insulin and HOMA-IR were greater in patients with the three FTO polymorphisms. There were significant interaction effects of the rs9930506 and rs1421085 FTO risk genotypes on weight and BMI in response to BS. No association was found with the MC4R polymorphism. The genotypes and haplotypes of the FTO gene influence post-surgery weight, TBWL, insulin levels, and HOMA-IR.

Analysis of Factors Associated with Outcomes of Bariatric Surgery: rs1800497 ANKK1, rs1799732 DRD2 Genetic Polymorphisms, Eating Behavior, Hedonic Hunger, and Depressive Symptoms.

INTRODUCTION: A therapeutic approach to severe obesity is bariatric surgery (BS), which is considered an effective intervention for ameliorating comorbidities such as T2DM, hypertension, dyslipidemia, and cardiovascular diseases. Some polymorphisms are considered markers for addictive disorders and hedonic hunger. We analyzed factors associated with the outcomes of BS, including rs1800497 ANKK1 and rs1799732 DRD2 polymorphisms, eating behavior, hedonic hunger, and depressive symptoms. METHODS: We retrospectively selected 101 patients who underwent BS and agreed to participate. The previous conditions to BS, such as body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and comorbidities, were registered; the scholarship value was evaluated as the total number of years of scholarly education. To evaluate the post-surgery conditions of the participants, we took blood samples, anthropometric measures, and 3 questionnaires to evaluate eating behavior (TFEQ-R18), hedonic hunger (PFS), and depressive symptoms (PHQ-9). The ANKK1 rs1800497 and rs1799732 DRD2 polymorphisms were genotyped. RESULTS: The median total weight loss (TWL) was 34.7 kg, with a BMI of 33.8 kg/m2, 6 (4-8) years after BS. The TWL was positively associated with the TFEQ-R18 score (p = 0.006) and negatively associated with triglycerides (p = 0.011). rs1800497 ANKK1 was associated with TFEQ-R18 (OR = 1.13 (1.02-1.25), p = 0.009). We also found a negative correlation of pre-surgery BMI with scholarship (r = - 0.27, p < 0.05). CONCLUSION: The patients showed an improvement in metabolic and anthropometric parameters post-surgery. Interestingly, the ANKK1 Taq1A polymorphism was associated with eating behavior and scholarship with pre-surgery BMI, which may be considered predictors of BS outcomes.

Associations of nicotidamide-N-methyltransferase, FTO, and IRX3 genetic variants with body mass index and resting energy expenditure in Mexican subjects.

The enzyme nicotidamide-N-methyltransferase (NNMT) regulates adipose tissue energy expenditure through increasing nicotinamide adenosine dinucleotide (NAD+) content. NNMT methylates nicotinamide to N1-methylnicotidamide (MNA-1) using S-adenosyl methionine. The rs694539 NNMT polymorphism is associated with non-alcoholic steatohepatitis, and rs1941404 is associated with hyperlipidemia. The rs1421085 FTO is related to poor eating behaviors, and rs3751723 IRX3 is associated with obesity. To investigate the association of rs694539 and rs1941404 NNMT, rs140285 FTO and rs3751723 IRX3 polymorphisms with MNA-1 concentrations, resting energy expenditure (REE) and BMI, we included clinically healthy Mexican subjects 30 to 50 years old, 100 subjects (35 men/65 women) with BMI > 30 kg/m2 and 100 subjects (32 men/68 women) with BMI < 25 kg/m2. Glucose, lipid profile, insulin, leptin, acylated ghrelin, and MNA-1 (LC-MS) were quantified. Resting energy expenditure (REE) was estimated using indirect calorimetry with a Fitmate instrument. Genotyping was performed using PCR-RFLP, and allelic discrimination was examined using TaqMan probes. MNA-1 concentrations and REE were significantly higher in obese subjects. Subjects with the rs694539AA NNMT genotype (recessive model) had lower weight, BMI, and REE. BMI showed an association with HDL-C, triglycerides, MNA-1, acetylated ghrelin, leptin, insulin concentrations, HOMA-IR, REE, and rs1421085. Subjects with the TC or CC genotypes of rs1421085 FTO showed 6 kg and 2 units of BMI more than did those with the TT wild type. The CG of the rs1421085 and rs3751723 haplotypes was associated with BMI. These findings showed that BMI was strongly associated with REE, rs1421085 FTO and the CG rs1421085 FTO and rs3751723 IRX3 haplotypes. We used the GMDR approach in obesity phenotype to show the interaction of four SNPs and metabolic variables.

Relationship of lactation, BMI, and rs12255372 TCF7L2 polymorphism on the conversion to type 2 diabetes mellitus in women with previous gestational diabetes.

Women with previous gestational diabetes mellitus (pGDM) have a high risk of developing postpartum type 2 diabetes mellitus (T2DM). This study aimed to analyze the relationship between lactation, BMI, and TCF7L2 polymorphisms in the conversion to T2DM in women with pGDM. One hundred and fifty-three women con pGDM were recruited from public hospitals of León Guanajuato México. Three groups: normal glucose tolerance (NGT), impaired glucose intolerance (IGT), and T2DM after the oral glucose tolerance test were formed. Metabolic and hormone variables were measured, and genotyping was made by PCR-RFLP. The questionnaire included data on lactation (yes/no), duration of lactation, and full lactation. After 35 (21-49) months from the last partum, 54% of women had an NGT, 30.7% IGT, and 15% T2DM. BMI and rs12255372 are associated with the risk of conversion to IGT and T2DM [OR = 1.07 (95% IC 1.0-1.14, p = .041; OR =2.14, 95% IC 1.01-4.55, p = .04 respectively), while the lactation shows a strong protective effects OR = 0.15 (95% IC 0.062-0.39, p = .00007), and an apparent interaction with rs12255372T decreasing the risk in carriers (OR =2.15; 95% IC 0.97-4.7, p = .05). BMI is an independent risk factor of IGT/T2DM development. The lactation shows a strong protective effect and a possible interaction with rs12255372 polymorphism.

Effects of sleeve gastrectomy and rs9930506 FTO variants on angiopoietin/Tie-2 system in fat expansion and M1 macrophages recruitment in morbidly obese subjects.

Angiogenesis in inflammation are hallmarks for adipose tissue expansion in obesity. The role of angiopoietin/Tie-2 system in adipose tissue expansion and immune cell recruitment is unclear. We studied the effect of sleeve gastrectomy and the influence of FTO rs9930506 polymorphism on Tie-2, angiopoietin-1 and angiopoietin-2 expression in morbid obesity. Fifteen morbidly obese subjects (4 men and 11 women) aged 24-55 years were followed-up 3 and 6 months after sleeve gastrectomy. Serum sTie-2, angiopoietin-1, angiopoietin-2, and hypoxia-inducible factor-1α concentrations were determined by ELISA. Tie-2 and its ligands in visceral and subcutaneous adipose tissue were localized by immunohistochemistry. Tie-2 expression was measured by flow cytometry in circulating monocytes and infiltrated macrophages. Comparisons before and after sleeve gastrectomy were carried out using ANOVA for repeated measures. rs9930506FTO genotyping was performed by PCR-RFLP. Circulating sTie-2 and angiopoietin-2 were higher before sleeve gastrectomy. Tie-2 and angiopoietin-2 mRNA levels were higher in subcutaneous adipose tissue than visceral and both decreased after surgery. Monocytes and infiltrated macrophages showed a pro-inflammatory phenotype, with increased Tie-2 expression that decreased 3 and 6 months after sleeve gastrectomy. Baseline sTie-2 correlated inversely with adiponectin levels. At baseline the rs9930506FTO AG ó GG genotypes carriers had more 34 kg than genotype carriers of rs9930506 AA. Weight and body mass index decreased at 6 months. We found that angiopoietin/Tie-2 system is mainly expressed in subcutaneous adipose tissue, contributing to expandability, fat accumulation, and monocytes attachment in obesity. Bariatric surgery favorably modifies the pro-angiogenic profile, allowed a reduced angiogenic expression in the circulation and adipose tissue.

Obesity is associated with the Arg389Gly ADRB1 but not with the Trp64Arg ADRB3 polymorphism in children from San Luis PotosÍ and León, México.

This research was designed to analyze the possible associations of Arg389Gly ADRB1 and Trp64Arg ADRB3 polymorphisms in children with obesity. A cross-sectional study included 1,046 school-age Mexican participants (6-12 years old) from the cities of San Luis PotosÍ and León. Children were classified as non-obese or obese according to their body mass index (BMI) percentile; obese children had a BMI≥95th percentile for sex and age. Biochemical data were collected. Polymorphisms were detected using TaqMan qPCR assay. A logistic regression analysis was used to calculate the risk of obesity based on genotypes. Differences were found between groups where obese children had a significant increase in systolic and diastolic blood pressure, fasting plasma glucose, insulin, HOMA-IR, LDL-cholesterol, triglycerides, and lower HDL-cholesterol compared with the normal weight group (P<0.05). The distribution of allele frequency in the population was Arg= 87.4 and Gly= 12.6 (Hardy Weinberg equilibrium c2 = 3.16 , P = 0.07 ); Trp= 81.5 and Arg= 18.5 (Hardy Weinberg equilibrium c2 = 2.2, P = 0.14 ) for ADRB1 and ADRB3, respectively. Even though no different frequencies of Arg389Gly polymorphism between groups were found (P = 0.08), children carriers of one Gly389 ADRB1 allele had a risk for obesity of OR=1.40 (95%CI, 1.03-1.90, P = 0.03) after adjustment for age and gender. No other association was found for Trp64Arg ADRB3 polymorphism. Only the Arg389Gly ADRB1 polymorphism was associated with risk for obesity in Mexican children.

Circulating profiling reveals the effect of a polyunsaturated fatty acid-enriched diet on common microRNAs.

BACKGROUND: Consumption of long-chain polyunsaturated fatty acids (PUFAs), which are abundant in seafood and nuts, ameliorates components of the metabolic syndrome. Circulating microRNAs (miRNAs) have demonstrated to be valuable biomarkers of metabolic diseases. Here, we investigated whether a sustained nuts-enriched diet can lead to changes in circulating miRNAs, in parallel to the dietary modification of fatty acids (FAs). METHODS AND RESULTS: The profile of 192 common miRNAs was assessed (TaqMan low-density arrays) in plasma from 10 healthy women before and after an 8-week trial with a normocaloric diet enriched with PUFAs (30 g/day of almonds and walnuts). The most relevant miRNAs were validated in an extended sample of 30 participants (8 men and 22 women). Adiponectin was measured by immunoassay and FAs by gas liquid chromatography coupled to mass spectrometry. The percentage of both ω-3 (P=.01) and ω-6 (P=.029) PUFAs of dietary origin (as inferred from plasma FA concentrations) increased, whereas saturated FAs decreased (P=.0008). Concomitantly with changes in circulating FAs, several miRNAs were modified by treatment, including decreased miR-328, miR-330-3p, miR-221 and miR-125a-5p, and increased miR-192, miR-486-5p, miR-19b, miR-106a, miR-769-5p, miR-130b and miR-18a. Interestingly, miR-106a variations in plasma correlated with changes in PUFAs, while miR-130b (r=0.58, P=.003) and miR-221 (r=0.46, P=.03) reflected changes in C-reactive protein. The dietary modulation of miR-125a-5p mirrored changes in fasting triglycerides (r=-0.44, P=.019) and increased adiponectin (r=0.43, P=.026). CONCLUSION: Dietary FAs (as inferred from plasma FA concentration) are linked to changes in circulating miRNAs, which may be modified by a PUFAs-enriched diet.

Modulation of the COMT Val(158)Met polymorphism on resting-state EEG power.

The catechol-O-methyltransferase (COMT) Val(158)Met polymorphism impacts cortical dopamine (DA) levels and may influence cortical electrical activity in the human brain. This study investigated whether COMT genotype influences resting-state electroencephalogram (EEG) power in the frontal, parietal and midline regions in healthy volunteers. EEG recordings were conducted in the resting-state in 13 postmenopausal healthy woman carriers of the Val/Val genotype and 11 with the Met/Met genotype. The resting EEG spectral absolute power in the frontal (F3, F4, F7, F8, FC3 and FC4), parietal (CP3, CP4, P3 and P4) and midline (Fz, FCz, Cz, CPz, Pz and Oz) was analyzed during the eyes-open and eyes-closed conditions. The frequency bands considered were the delta, theta, alpha1, alpha2, beta1 and beta2. EEG data of the Val/Val and Met/Met genotypes, brain regions and conditions were analyzed using a general linear model analysis. In the individuals with the Met/Met genotype, delta activity was increased in the eyes-closed condition, theta activity was increased in the eyes-closed and in the eyes-open conditions, and alpha1 band, alpha2 band and beta1band activity was increased in the eyes-closed condition. A significant interaction between COMT genotypes and spectral bands was observed. Met homozygote individuals exhibited more delta, theta and beta1 activity than individuals with the Val/Val genotype. No significant interaction between COMT genotypes and the resting-state EEG regional power and conditions were observed for the three brain regions studied. Our findings indicate that the COMT Val(158)Met polymorphism does not directly impact resting-state EEG regional power, but instead suggest that COMT genotype can modulate resting-state EEG spectral power in postmenopausal healthy women.

Metabolic, hormonal characteristics and genetic variants of TCF7L2 associated with development of gestational diabetes mellitus in Mexican women.

BACKGROUND: Variation in TCF7L2 gene is associated with type 2 diabetes and with gestational diabetes mellitus in several populations, but there are no data in Mexican women with gestational diabetes mellitus. In this study, we examined metabolic and hormonal measurements as well as TCF7L2 genetic variants. METHODS: We selected 108 pregnant women with normal glucose tolerance and 90 with gestational diabetes mellitus according to 2010 American Diabetes Association criteria matched for gestational week. We collected data on blood pressure, body mass index (BMI) and concentrations of blood glucose, HbA1c , lipids profile, insulin and glucagon-like peptide-1 (GLP-1). The genotyping of rs7903146 and rs12255372 polymorphisms were made with polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Actual and pre-gestational BMI, fasting glucose and HbA1c were higher (p < 0.001), and high-density lipoprotein cholesterol was lower (p < 0.02) in gestational diabetes mellitus women than euglycemic women. No significant differences were found for lipids, insulin and homeostasis model assessment-insulin resistance. Gestational diabetes mellitus women had high GLP-1 levels (32 vs 24, p < 0.004) and decreased ß-cell function (266 vs 438, p < 0.001). The frequency of rs12255372 risk allele in gestational diabetes women was significantly higher than that in euglycemic women (χ² = 8.96; p < 0.003) and confers a risk for gestational diabetes mellitus (OR = 9.1, 95% CI 2.8-29, p < 0.0002; and OR = 4.3, 95% CI 1.6-11.4, p < 0.003 based on dominant and co-dominant model, respectively). The generalized linear model showed that low beta function, high pre-gestational BMI and rs12255372 risk allele are independently associated with gestational diabetes. CONCLUSIONS: The elevated GLP-1 levels in gestational diabetes women suggested some abnormality in insulin secretion. The low ß-cell function, high pre-gestational BMI and rs12255372 risk allele are risk factors independently associated with the development of gestational diabetes.

Analysis of the contribution of FTO, NPC1, ENPP1, NEGR1, GNPDA2 and MC4R genes to obesity in Mexican children.

BACKGROUND: Recent genome wide association studies (GWAS) and previous positional linkage studies have identified more than 50 single nucleotide polymorphisms (SNPs) associated with obesity, mostly in Europeans. We aimed to assess the contribution of some of these SNPs to obesity risk and to the variation of related metabolic traits, in Mexican children. METHODS: The association of six European obesity-related SNPs in or near FTO, NPC1, ENPP1, NEGR1, GNPDA2 and MC4R genes with risk of obesity was tested in 1,463 school-aged Mexican children (N(cases) = 514; N(controls) = 949). We also assessed effects of these SNPs on the variation of body mass index (BMI), fasting serum insulin levels, fasting plasma glucose levels, total cholesterol and triglyceride levels, in a subset of 1,171 nonobese Mexican children. RESULTS: We found a significant effect of GNPDA2 rs10938397 on risk of obesity (odds ratio [OR] = 1.30; P = 1.34 × 10-3). Furthermore, we found nominal associations between obesity risk or BMI variation and the following SNPs: ENPP1 rs7754561, MC4R rs17782313 and NEGR1 rs2815752. Importantly, the at-risk alleles of both MC4R rs17782313 and NPC1 rs1805081 showed significant effect on increased fasting glucose levels (ß = 0.36 mmol/L; P = 1.47 × 10(-3)) and decreased fasting serum insulin levels (ß = -0.10 µU/mL; P = 1.21 × 10(-3)), respectively. CONCLUSION: Our present results suggest that some obesity-associated SNPs previously reported in Europeans also associate with risk of obesity, or metabolic quantitative traits, in Mexican children. Importantly, we found new associations between MC4R and fasting glucose levels, and between NPC1 and fasting insulin levels.

Symptoms at postmenopause: genetic and psychosocial factors.

OBJECTIVE: Menopause symptoms result from the interaction of estrogen deprivation, psychosocial influences, and genetic factors. We examined the influence of stress and of estrogen receptor-α (ER-α; PvuII and XbaI) and serotonin transporter (5-HTT) polymorphisms on symptoms at postmenopause. METHODS: We studied 290 urban women from three cities in Mexico. General characteristics, menopause symptoms, and scores of perceived stress, effort-reward imbalance, dominance, and submission were collected. A fasting blood sample was obtained for hormone measurements and genotypification. RESULTS: Women had a mean ± SD age of 54.4 ± 4.5 years and BMI of 29.5 ± 4.9 kg/m. The frequency of hot flashes was 75.5%; vaginal dryness, 57.8%; and diminished sexual interest, 78.7%. Follicle-stimulating hormone and estradiol levels were 59 ± 27 mIU/mL and 22 ± 29 pg/mL, respectively. Women from Torreón had higher schooling and less parity but higher scores for depression and lower submission. Hot flashes were more frequent in women from León. Genotype distribution was similar among cities. Lower scores for dominance were found in women with the pp and xx ER-α genotypes. Increased smoking habit was found for the SS genotype of 5-HTT. Factors significantly associated with symptoms were years since menopause, with hot flashes (negative), and with diminished sexual interest (positive); dominance was negatively associated with depression, perceived stress, and vaginal dryness; submission was positively associated with depression, perceived stress, anxiety, and hot flashes; and effort-reward imbalance was positively associated with anxiety, hot flashes, and perceived stress. CONCLUSIONS: Symptoms at postmenopause were associated mainly with dominance, submission, and effort-reward imbalance. The pp genotype of ER-α showed lower scores of dominance.

Association of the TNF-α -308G/A polymorphism with family history of type 2 diabetes mellitus in a Mexican population.

AIMS: We examined the possible association of the -308G/A polymorphism of the TNF-α promoter gene in type 2 diabetes mellitus (DM2) patients and in non-diabetic subjects with and without family history of DM2. METHODS: We studied 87 non-diabetic subjects without DM2 family history in at least one of two generations, 48 non-diabetic subjects with DM2 family history and 95 DM2 patients. Genotyping was carried out by PCR-RFLP. RESULTS: The frequency of TNF-α -308G/A genotype was significantly lower in non-diabetic subjects without DM2 relatives (6%) as compared to DM2 patients (24%) (odds ratio (OR)=5.24; 95% confidence interval (CI)=1.9-15.8, p<0.0005), but similar to non-diabetic subjects with DM2 relatives (29%) (OR=0.77; CI=0.3-1.7, p=0.4). Logistic regression analysis showed the association of TNF-α -308G/A polymorphism with DM2 family history (OR=5.80; CI=1.77-18.98, p<0.0003). CONCLUSIONS: Our results suggest that TNF-α -308G/A polymorphism is associated with DM2 family history and is a risk factor for DM2.

Expression of estrogen receptor alpha and beta in breast cancers of pre- and post-menopausal women.

Expression of estrogen receptors (ER) is clinically relevant in designing therapeutic strategies. The relative importance of the two types of estrogen receptors (ER-alpha and ER-beta) in human breast cancers in pre- and post-menopausal women has not been properly defined. To determine the possible association between the expression of estrogen receptor and serum estradiol levels in pre- and post-menopausal women with breast cancer. 44 patients with invasive ductal carcinoma of the breast were studied and a breast tissue biopsy was taken. ER-alpha and ER-beta were detected by immunocytochemistry. Serum levels of estradiol and estrone were measured by radioimmunoassay and FSH was measured using IRMA. We studied 21 pre- and 23 post-menopausal women with breast carcinoma. Examining the number of cases with tumors positive for ER, we found no differences in the frequency of ER-alpha between pre- and post-menopausal women, but ER-beta decreased marginally after menopause (p < 0.051). In cases with tumors positive for ER, the proportion of cells positive for ER-alpha was similar post-menopausally (53.95%) and pre-menopausally (57.21%), but for ER-beta the number of positive cells decreased significantly after menopause (p < 0.051). In pre-menopausal women there was a correlation between serum estradiol levels and ER-beta; in post-menopausal women there was a correlation between serum FSH levels and ER-alpha. These results indicate that estradiol levels in women with mammary carcinoma are related to ER-beta expression in the breast tumor tissue.

Serum selenium and glutathione peroxidase concentrations in type 2 diabetes mellitus patients.

AIMS: Antioxidant selenium (Se) properties and, its protective role against oxidative damage play an important role in diabetic complications. Our objective was to gain further insight on a link between selenium status and diabetic nephropathy. METHODS: We assessed glutathione peroxidase (GPx) and Se in type 2 diabetes mellitus patients with microalbuminuria (MA) (group 1), without microalbuminuria (group 2), and in control subjects (group 3). Glucose, urea, creatinine and glycated hemoglobin tests were tested in sera. A complete clinical record was elaborated. RESULTS: For diabetic patients both, the time from diagnosis and plasma glucose concentration were higher in group 1 as compared to group 2. Control group showed higher serum Se concentrations as compared to the diabetic groups. The two groups of diabetic patients showed similar serum Se levels. Serum concentration of GPx was significantly lower in group 1 as compared to groups 2 and 3. Microalbuminuria (MA) test showed a positive correlation with glucose, and a negative relationship with serum Se and GPx. Multiple regression revealed an inverse relationship between selenium or GPx in serum and the results of the MA test. CONCLUSIONS: Our results suggest that lower Se and GPx levels in diabetic patients may be implicated in the diabetic nephropathy.

Effect of the Pro12Ala polymorphism of the PPAR gamma 2 gene on response to pioglitazone treatment in menopausal women.

OBJECTIVE: To investigate the influence of the Pro12Ala polymorphism of the PPAR gamma 2 gene on metabolic and hormonal response to pioglitazone treatment in obese postmenopausal women. DESIGN: We included 102 obese (body mass index [BMI] >or=30 kg/m2) and 97 nonobese (BMI

[Symptomatic profile in peri and postmenopausal women]. / Perfil sintomático en mujeres peri y posmenopáusicas.

OBJECTIVE: To determine the symptoms that women refer during peri and postmenopause. PATIENTS AND METHOD: A cross-sectional study was carried out from April to December 2005; 500 women between 45 and 65 years old were included. We applied them the NR 1 questionnaire of symptoms for mature women. Data were obtained by means of a face-to-face interview. Results were analyzed through descriptive statistics, with percentage values, arithmetic mean and standard deviation. Differences between groups were evaluated with Student's T test, chi square test, and Fisher exact test. RESULTS: Perimenopausal women had higher levels of depression (p = 0.03). Postmenopausal women presented higher frequency of sleep disturbances (p = 0.003). We found that perimenopausal women had more night sweats (p = 0.005), excessive hot (p = 0.006), hot flashes (p = 0.001), headaches (p = 0.001), vaginal dryness (p = 0.03), and dyspareunia (p = 0.005). On the other hand, postmenopausal women presented higher frequency of changes in libido (p = 0.001). CONCLUSIONS: In general, perimenopausal women have more symptoms than posmenopausal women. It is advisable an exhaustive analysis of the perimenopausal women symptoms in order to offer them an integral substitutive treatment.

Factors associated with estrogen receptors-alpha (ER-alpha) and -beta (ER-beta) and progesterone receptor abundance in obese and non obese pre- and post-menopausal women.

There is scarce information about the factors associated with estrogen receptors (ER) at menopause. In 113 volunteers pre- and post-menopausal healthy women, grouped as with and without obesity, estrogen receptors-alpha and -beta, and progesterone receptor (PR) were measured by immunohistochemistry in skin punch biopsies obtained from the external gluteal area. In pre-menopausal women, biopsies and a blood sample were performed between days 7 and 14 of the cycle. Serum hormone levels were measured by immunoradiometric assay or radioimmunoassay. After menopause, ER and PR amounts decreased significantly. At pre-menopause, obese women had lower PR levels than non obese (P<.006). In the post-menopausal group, obese women showed higher ER-alpha (P<.03) and ER-beta (P<.02) levels than the non obese group. In the analysis of factors associated with the amount of steroid receptors for the total group, log[ER-alpha], log[ER-beta], and log[PR] were associated with age (P<.002, <.005, and <.004, respectively). The log[ER-alpha] was also associated with log[FSH] (P<.0008); meanwhile, the log[PR] showed a marginal correlation with log[FSH]. In pre-menopausal women no factor associated with any of the three receptors was found. In post-menopausal women log[ER-alpha] was associated with log[estrone] and log[DHEAS] (P<.003 and <.02, respectively). log[PR] was associated with BMI (P<.002), years since menopause (P<.05), and log[DHEAS] (P<.003). We concluded that ER and PR diminish sharply at post-menopause. At this stage the amount of receptors depends on several factors such as BMI, years since menopause, and androgen precursors.

Occupational exposure to toluene and its possible causative role in renal damage development in shoe workers.

OBJECTIVES: An important, although, unprecise number of shoe workers in Leon, Mexico, are in continuous contact with toluene-based glues. The induction of renal glomerular and/or tubular lesions as a result of toluene exposure is still being discussed controversially. Our objective was to evaluate the extent of occupational exposure, assessing urinary o-Cresol excretion as a measure for toluene exposure in a population at risk as compared to a control population. Urinary albumin excretion (UAE) and N-acetyl-beta-D-glucosaminidase (NAG) enzymatic activity were tested to assess renal dysfunction. METHODS: A cross-sectional study was performed comparing 50 toluene-exposed shoe workers and 25 control subjects. Urinary o-cresol was assessed on first and last day of labor week from exposed subjects. A single urine sample was obtained from control subjects. Urinary Albumin excretion (UAE) and (NAG) activity were examined in 12 h urine samples in all subjects. Urine and serum creatinine were measured to asses renal function. RESULTS: At the end of the labor week, urinary o-cresol levels were higher in samples obtained from exposed subjects. Albumin excretion was similar in the exposed and control groups. NAG activity was greater in the exposed group compared to control group (median 3.5 U/g creatinine vs 1.9 U/g creatinine, z=2.6, P=0.009). An inverse relationship was found between schooling years and the NAG enzymatic activity for the two studied groups (r= -0.27, P=0.02), CONCLUSIONS: Our findings support the hypothesis that toluene may be a factor associated with the presence of renal damage in exposed shoe workers. As NAG activity is increased, we believe the lesion initiates in the renal tubular cells.

[Breast density and its association to polimorphism of the estrogen-receptor alpha gene Pvull and Xbal]. / Densidad mamaria y su asociación con el polimorfismo del gen del receptor de estrógenos alfa (REalpha) Pvull y Xbal.

OBJECTIVE: To study the influence of ER-alpha on mammographic density. MATERIAL AND METHODS: We selected 87 healthy women (age 49.8 +/- S.D. 6.12 years). We obtained the body mass index (BMI), and a fasting blood sample for hormone determinations and DNA extraction. ER-alpha genotyping was carried out by PCR and digestion with a Pvull and Xbal restriction endonucleases. Mammographic density was assigned by the radiologist used three categories of fatty, average and dense. RESULTS: Mammographic density was significantly associated with estradiol (p = 0.04), estrone (p = 0.04), and FSH (p = 0.02). The BMI was not associated with Pvull and Xbal genotypes and marginally with mammographic breast density (p = 0.06). CONCLUSIONS: We did not observe compelling evidence of an association between variant alleles of genotypes estrogen receptors alpha and breast density.

The relationship of estrogen receptor-alpha polymorphism with symptoms and other characteristics in post-menopausal women.

OBJECTIVES: To study the influence of the estrogen receptor-alpha (ER-alpha) genotypes (PvuII and XbaI polymorphisms) on symptoms and bone density. METHODS: We recruited 177 post-menopausal women to register hot flashes, vaginal dryness, depression, anxiety, sleep alterations, and serum hormones (FSH, LH, estrone, and estradiol). Bone mineral density (BMD) was measured with a radiographic method, correcting with an external reference. ER-alpha genotyping was carried out by PCR. RESULTS: Scores for vaginal dryness were lower for the xx (P = 0.003), and pp genotypes (P = 0.006). Hot flashes were lower for the Pp (P = 0.006) genotype. FSH circulating levels were lower for Xx genotype (P = 0.036). The factors associated with BMD were estrone (P > 0.000001), estradiol (P = 0.0035) and XbaI (P = 0.035). Vaginal dryness, was associated with PvuII and XbaI polymorphisms (P = 0.037 and P = 0.039). Depression was associated with log(estrone) (P = 0.011), schooling (negatively, P = 0.012), and marginally with BMI (P = 0.066). Sleep alterations correlated with log(estrone) (P = 0.014) and marginally with years since menopause (P = 0.046). Anxiety correlated with schooling (negatively, P = 0.006) and age (p = 0.015), and hot flashes with schooling (negatively, P = 0.014). BMD was associated with log(estrone) (p < 0.000001), estradiol (negatively, P = 0.0036), and marginally with XbaI (P = 0.036). CONCLUSIONS: In post-menopausal women, the ER-alpha polymorphism was associated with vaginal dryness, and hot flashes but not with other physical or emotional symptoms. Extraglandular estrogen production, and diverse molecular factors related to estrogen action may play an important role in this process.