A miRNA-Based Blood and Mucosal Approach for Detecting and Monitoring Celiac Disease.

BACKGROUND: The role of microRNAs (miRNAs) in celiac disease (CD) is unclear. AIMS: We evaluated inflammation-related miRNA-146a, miRNA-155, miRNA-21, and miRNA-125b expression in peripheral blood and intestinal mucosa of CD adults. METHODS: Thirty patients with CD were included: patients with active CD on a gluten-containing diet (CD-active, n = 10), patients on a gluten-free diet (for at least 1 year), and patients with negative blood antibodies (CD-inactivePE, n = 10). In addition, ten healthy volunteers formed the comparison/control group. MiRNA expression was measured in duodenal biopsies from patients (CD-inactiveMU, n = 10) after in vitro exposure to PT gliadin and 33-mer peptide. MiRNAs expression was measured in plasma and in peripheral blood mononuclear cells (PBMCs) and monocytes, before and after in vitro exposure to native gliadin (gliadinN). RESULTS: Expression levels of miRNA-146a, miRNA-155, and miRNA-21 in PBMCs, miRNA-155 in monocytes and miRNA-155, miRNA-21, and miRNA-125b in plasma were elevated in both groups of celiac patients. After in vitro exposure with gliadinN, miRNA-146a and miRNA-155 expression markedly increased in PBMCs and monocytes, while miRNA-155 and miRNA-21 increased in the CD-active group. MiRNAs expression in intestinal mucosa did not change. MiRNA-146a and miRNA-155 expression showed high sensitivity and specificity for the presence of CD, irrespective of the current dietary treatment. CONCLUSIONS: Selected inflammation-related miRNAs expression is elevated in the peripheral blood of celiac. This suggests their participation in the immune processes underlying the pathology. Their similar response in active and inactive CD suggests that they should be further evaluated, as potential diagnostic biomarkers for CD.

Avoiding Small Intestinal Biopsies for Diagnosis of Celiac Disease in Children: A Reliable Strategy for All Patients?

BACKGROUND: Current reports applying ESPGHAN exception criteria (EEC) to diagnose celiac disease (CD) without duodenal biopsies indicate that a high percentage of patients with CD may be identified when applied correctly in specialized settings. Application of the EEC, however, in "daily life conditions" at the different levels of medical services is not clear. METHODS: EEC was applied to 130 pediatric patients evaluated for CD at 5 public hospitals in Santiago, Chile, during 2010 to 2015. Clinical presentation, serum anti-tissue transglutaminase 2 and anti-endomysium antibodies (EMA), genotyping, and small intestinal histology were obtained from clinical charts. RESULTS: A total of 78 of 130 patients reviewed had some of the data required for analysis, but EMA was determined in 54% and genotyping in 2.3% of patients, limiting the study. After offering free genotyping, only 12 of 78 (15%) had all data required for EEC application. In this small group, 10 of 12 (83.3%) patients could avoid duodenal biopsies and 2 (16.7%) with potential CD were misdiagnosed. Main reasons for not doing EMA and genotyping were that they are expensive, unavailable in the local health care center, and considered "not necessary" for diagnosis. CONCLUSION: Limited resources in clinical settings reduce availability of EMA and genotyping, making application of EEC criteria difficult and only possible only in 15% of our patients. Within this subgroup, biopsies could be avoided in 83.3%, and 16.7% of patients with potential CD were misdiagnosed. Insufficient studies and incorrect interpretation of EEC contributed to incomplete assessment in 52 of 130 (40%) patients. The Chilean public health system is likely representative of several others present in developing and developed countries.

[Association between FTO (ns9939609) genotype and adiposity markers in Chilean adults]. / Asociación entre el polimorfismo rs9939609 del gen FTO y marcadores de adiposidad en población adulta chilena.

BACKGROUND: Numerous studies have identified the role of Fat-mass-associated-gene (FTO) in the development of obesity. AIM: To investigate the association of FTO gene with adiposity markers in Chilean adults. MATERIAL AND METHODS: 409 participants were included in this cross-sectional study. The association between FTO (rs9939609) genotype and adiposity markers was determined using linear regression analyses. Adiposity markers included were: body weight, body mass index, fat mass, waist circumference, hip circumference and waist/hip ratio. RESULTS: A fully adjusted model showed a significant association between FTO genotype and body weight (2.16 kg per each extra copy of the risk allele [95% confidence intervals (CI): 0.45 to 3.87], p = 0.014), body mass index (0.61 kg.m-2 [95% CI: 0.12 to 1.20], p = 0.050) and fat mass (1.14% [95% CI: 0.39 to 1.89], p = 0.010). The greater magnitude of association was found between the FTO gene and fat mass when the outcomes were standardized to z-score. CONCLUSIONS: This study confirms an association between the FTO gene and adiposity markers in Chilean adults, which is independent of major confounding factors.

Epigenetics in type 1 diabetes: TNFa gene promoter methylation status in Chilean patients with type 1 diabetes mellitus.

TNF-α is a pro-inflammatory cytokine that is involved in type 1 diabetes (T1D) pathogenesis. The TNFa gene is subject of epigenetic regulation in which folate and homocysteine are important molecules because they participate in the methionine cycle where the most important methyl group donor (S-adenosylmethionine) is formed. We investigated whether TNFa gene promoter methylation status in T1D patients was related to blood folate, homocysteine and TNF-α in a transversal case-control study. We studied T1D patients (n 25, mean=13·7 years) and healthy control subjects (n 25, mean=31·1 years), without T1D and/or other autoimmune diseases or direct family history of these diseases. A blood sample was obtained for determination of serum folate, plasma homocysteine and TNF-α concentrations. Whole blood was used for the extraction of DNA to determine the percentage of methylation by real-time PCR and melting-curve analysis. Results are expressed as means and standard deviations for parametric variables and as median (interquartile range) for non-parametric variables. T1D patients showed a higher TNFa gene promoter methylation (39·2 (sd 19·5) %) when compared with control subjects (25·4 (sd 13·7) %) (P=0·008). TNFa gene promoter methylation was positively associated only with homocysteine levels in T1D patients (r 0·55, P=0·007), but not in control subjects (r -0·122, P=0·872). To our knowledge, this is the first work that reports the methylation status of the TNFa gene promoter and its relationship with homocysteine metabolism in Chilean T1D patients without disease complications.

Elevation of C-reactive protein during the luteal phase in healthy adolescents.

INTRODUCTION: Variations in inflammatory markers have been reported in adult women during the luteal phase, but whether these findings are observed during adolescence is unknown. We postulate that higher ultrasensitive C-reactive protein (usCRP) and lower 2-hydroxyestrone (2OHE) levels, an estrogen metabolite with cardioprotective actions, are present during the luteal phase in young women. AIM: To evaluate usCRP levels during the menstrual cycle and to determine its association with 2OHE and 16α-hydroxyestrone (16OHE) in adolescents. METHODS: Healthy postmenarcheal adolescents (N = 37) were studied during one menstrual cycle in follicular phase (FP) and luteal phase-like period (LP-L). RESULTS: Elevations in usCRP levels in the LP-L were observed in the entire group and in anovulatory cycles (1.9 ± 1.1 mg/L in FP to 2.5 ± 1.8 mg/L in LP-L; p < 0.0001). Increases in estrone, estradiol, free and bioavailable estradiol, testosterone, usCRP and 2OHE levels were observed in LP-L compared with FP (p < 0.01), with a borderline elevation in IFG-I levels (p = 0.06). CONCLUSIONS: We report an elevation of usCRP and 2OHE levels during the luteal phase in healthy adolescents. Elevations of this inflammatory marker in anovulatory adolescents without an increase in 2OHE may play a role in metabolic risks associated with chronic anovulation.

[Global DNA methylation and homocysteine levels are lower in type 1 diabetes patients]. / La metilación global del ADN y los niveles de homocisteína en plasma se encuentran disminuidos en pacientes con diabetes mellitus tipo 1.

BACKGROUND: The worldwide rise in the incidence of Type 1 Diabetes (T1D), and the concordance rate between monozygotic twins (50%), indicate a strong effect of the environment as an underlying factor of this disease. This process can occur throughout epigenetic modifications of gene expression such as DNA methylation, in which several nutrients participate as cofactors. AIM: To determine DNA methylation status in T1D patients and if it is related to plasma levels of folates and homocysteine (Hcy). MATERIAL AND METHODS: We obtained blood samples from 25 T1D patients aged 13.7 ± 5.9 years (11 males) and 25 healthy subjects aged 31.1 ± 7.8 years (16 males). DNA methylation was measured using a colorimetric kit in extracted DNA. Results are expressed as median (interquartile range). RESULTS: Compared with healthy controls, T1D patients had lower global DNA methylation (0.85 (0.91) % and 1.25 (1.16) % respectively, p < 0.02) and Hcy levels (4.8 (1.1) µmol/L and 7.3 (1.4) µmol/L respectively p < 0.01). There were no differences in folate levels between groups. A significant association between folates and global DNA methylation status was observed in T1D patients (r = -0.564, p < 0.01) and healthy subjects (r = 0.440, p = 0.03). CONCLUSIONS: TD1 patients had lower levels of Hcy and global DNA methylation. It is relevant to further investigate if this imbalance also induces epigenetic changes in a gene-specific manner, especially in key genes involved in T1D pathogenesis.

[Insulin autoimmune syndrome: Report of two cases]. / Síndrome de hipoglicemia autoinmune: Primeros casos en Chile.

Insulin autoimmune syndrome (IAS) is characterized by spontaneous hypoglycemia with extremely high insulin levels and the presence of circulating autoantibodies against insulin, in patients who have never been exposed to exogenous insulin. We report two patients with the syndrome. A 36 years old male presenting with hypoglycemia in the emergency room had an oral glucose tolerance test showed basal and 120 min glucose levels of 88 and 185 mg/dl. The basal and 120 min insulin levels were 2,759 and 5,942 µUI/ml. The presence of an insulin secreting tumor was discarded. Anti-insulin antibodies were positive. He was successfully treated with a diet restricted in carbohydrates and frequent meals in small quantities. A 65 years old female presenting with hypoglycemia in the emergency room had the fasting insulin levels of 1,910 µUI/ml. No insulin secreting tumor was detected by images and anti-insulin antibodies were positive. The polyethylene glycol precipitation test showed a basal and after exposition insulin level 1,483 and 114 µUI/ml, respectively. She responded partially to diet and acarbose and required the use of prednisone with a good clinical response.

[Effect of supplementation with a single dose of vitamin D in children with cerebral palsy. Preliminary randomised controlled study]. / Efecto de la suplementación con vitamina D en monodosis en niños con parálisis cerebral. Estudio preliminar controlado y aleatorizado.

INTRODUCTION: Children with cerebral palsy (CP) have an increased risk of vitamin D (VD) deficiency. Although there are many studies on VD and CP, there is limited information about VD supplementation in these patients. OBJECTIVE: To evaluate the effect of supplementation with a single dose of VD on the plasma concentrations of 25-hydroxy-vitamin-D (25OHD) in children with CP. PATIENTS AND METHOD: Prospective-randomised-controlled-trial, including 30 Chilean children (19 males) with CP, median age 9.9 years (6.2-13.5). Clinical and biochemical variables including 25OHD, were recorded (time 0 and 8 weeks). Patients were allocated to the supplemented (S) group receiving 100,000 IU oral D3 at baseline, and compared with the placebo (P) group. RESULTS: Among clinical features are highlighted: gastrostomy (60%), underweight (30%), bed-ridden (93.3%), antiepileptic drugs (70%), and 43.3% used VD metabolism inducing antiepileptics. Baseline biochemical measurements were normal. The 25OHD was insufficient in 4/30 and deficient in 6/30. 25OHD levels were not associated with the variables studied. Eight patients completed the study in the S group, and 10 in P group. The placebo and supplementation groups had no significant difference in baseline variables. Serum calcium, phosphate, and alkaline phosphatase levels at 8 weeks were normal in both groups, with no statistically significant differences. 25OHD in the P group was normal in 6/10, and insufficient+deficient in 4/10, and the S group was normal in all (8/8) (exact Fisher test P=.07). CONCLUSIONS: A single dose of 100,000 IU VD could normalise the concentrations of 25OHD after 8 weeks of supplementation in Children with CP, but more studies are required to confirm these results.

PD-L1 gene polymorphisms and low serum level of PD-L1 protein are associated to type 1 diabetes in Chile.

INTRODUCTION: Type 1 diabetes (T1D) has a complex etiology in which genetic and environmental factors are involved, whose interactions have not yet been completely clarified. In this context, the role in PD-1 pathway and its ligands 1 and 2 (PD-L1 and PD-L2) have been proposed as candidates in several autoimmune diseases. The aim of this work was to determine the allele and haplotype frequency of six gene polymorphisms of PD-ligands (PD-L1 and PD-L2) in Chilean T1D patients and their effect on serum levels of PD-L1 and autoantibody profile (GAD65 and IA2). METHODS: This study cohort comprised 205 T1D patients and 205 normal children. We performed genotypic analysis of PD-L1 and PD-L2 genes by TaqMan method. Determination of anti-GAD65 and anti-IA-2 autoantibodies was performed by ELISA. The PD-L1 serum levels were measured. RESULTS: The allelic distribution of PD-L1 variants (rs2297137 and rs4143815) showed differences between T1D patients and controls (p = 0.035 and p = 0.022, respectively). No differences were detected among the PD-L2 polymorphisms, and only the rs16923189 showed genetic variation. T1D patients showed decreased serum levels of PD-L1 compared to controls: 1.42 [0.23-7.45] ng/mL versus 3.35 [0.49-5.89] ng/mL (p < 0.025). In addition, the CGG haplotype in PD-L1 associated with T1D (constructed from rs822342, rs2297137 and rs4143815 polymorphisms) showed an OR = 1.44 [1.08 to 1.93]. Finally, no association of these genetic variants was observed with serum concentrations of PD ligands or auto-antibody profile, although a correlation between PD-L1 ligand serum concentration and the age at disease onset was detected. CONCLUSION: Two polymorphism of PD-L1 are presented in different allelic variants between T1D and healthy subjects, also PDL-1 serum levels are significantly lowered in diabetics patients. Moreover, the age of onset of the disease determine differences between serum ligand levels in diabetics, being lower in younger. These results points to a possible establishment of PDL-1 as a genetic and biochemical marker for T1D onset, at least in Chilean population.

MicroRNAs: an epigenetic tool to study celiac disease.

This article summarizes recent findings on the role of microRNAs (miRNAs) in biological processes associated with the regulation of chronic inflammation and autoimmunity. miRNAs are small non-coding RNA molecules that have been recently emerged as a new class of modulators of gene expression at the post-transcriptional level. MiRNAs bind to complementary sequences of specific targets of messengers RNA, which can interfere with protein synthesis. We reviewed studies that evaluated the expression patterns of miRNAs in different autoimmune diseases, especially in celiac disease (CD). CD is a chronic enteropathy triggered by gluten proteins, characterized by altered immune responses in genetically susceptible individuals that results in damage to the bowel mucosa. CD has a high prevalence and an effective treatment by a specific diet ("gluten free diet"). Genetic factors confer susceptibility but do not explain the whole disease, suggesting that environmental factors do play a relevant role in the development of the condition.The evaluation of the potential role of miRNA is of particular interest in CD given that these epigenetic mechanisms in the pathogenesis of autoimmune and inflammatory diseases have been recently described. Improving our understanding of miRNAs in CD will contribute to clarify the role of altered epigenetic regulation in the development and course of this disease.

[Prevalence of metabolic syndrome in Mapuche individuals living in urban and rural environment in Chile]. / Prevalencia de síndrome metabólico en individuos de etnia Mapuche residentes en zonas rurales y urbanas de Chile.

BACKGROUND: Metabolic Syndrome (MS) increases the risk of diabetes and mortality associated with cardiovascular disease. However, the prevalence of MS could differ by ethnicity and lifestyle factors. AIM: To determine the prevalence of MS in Mapuche individuals living in urban and rural environments in Chile and to investigate whether the prevalence and risk of MS in urban and rural environments differs by sex, age and nutritional status. MATERIAL AND METHODS: A total of 1077 Mapuche participants were recruited from urban (MU = 288) and rural (MR = 789) settings. Body mass index, waist circumference and blood pressure were measured. A fasting blood sample was obtained to measure serum glucose, HDL cholesterol and triacylglycerol. The prevalence of MS was determined using the unified IDF and ATP-III criteria. RESULTS: An environment and sex interaction was found for the prevalence of MS (p = 0.042). The prevalence was significantly lower in male MR (13%) compared to other groups (22, 23 and 25% among female MR, female MU and male MU respectively). Also, the prevalence of central obesity and low HDL-cholesterol were significantly lower in male MR. MU are at an increased risk of developing MS compared to MR, with an odds ratio of 1.59 (95% confidence intervals 1.1 to 2.2). This risk increases along with age or body mass index of the population. CONCLUSIONS: The adoption of an urbanized lifestyle increases the risk of developing MS in Mapuche individuals. This risk is enhanced by age and nutritional status.

Sucralose and stevia consumption leads to intergenerational alterations in body weight and intestinal expression of histone deacetylase 3.

OBJECTIVES: It is unclear whether parental consumption of non-nutritive sweetener (NNS) can affect subsequent generations. The aim of this study was to determine whether chronic parental consumption of sucralose and stevia in mice affects body weight gain and liver and intestinal expression of histone deacetylase 3 (Hdac3) in these animals and in the subsequent first filial (F1) and second filial (F2) generations. METHODS: Male and female mice (n = 47) were divided into three groups to receive water alone or supplemented with sucralose (0.1 mg/mL) or stevia (0.1 mg/mL) for 16 wk (parental [F0] generation). F0 mice were bred to produce the F1 generation; then, F1 mice were bred to produce the F2 generation. F1 and F2 animals did not receive NNSs. After euthanasia, hepatic and intestinal expression of Hdac3 was determined by quantitative reverse transcription polymerase chain reaction. RESULTS: Body weight gain did not differ between the three groups in the F0 generation, but it was greater in the F1 sucralose and stevia groups than in the control group. Consumption of both NNSs in the F0 generation was associated with lower Hdac3 expression in the liver and higher in the intestine. Hepatic Hdac3 expression was normalized to the control values in the F1 and F2 animals of the sucralose and stevia groups. Intestinal expression was still higher in the F1 generations of the sucralose and stevia groups but was partially normalized in the F2 generation of these groups, compared with control. CONCLUSIONS: NNS consumption differentially affects hepatic and intestinal Hdac3 expression. Changes in hepatic expression are not transmitted to the F1 and F2 generations whereas those in intestinal expression are enhanced in the F1 and attenuated in the F2 generations.

Zinc as a potential coadjuvant in therapy for type 2 diabetes.

BACKGROUND: Type 2 diabetes is highly prevalent in populations having high rates of overweight and obesity. It is a chronic condition responsible for long-term severe dysfunction of several organs, including the kidneys, heart, blood vessels, and eyes. Although there are a number of pharmacologic products in the market to treat insulin resistance and impaired insulin secretion--the most prominent features of this disease--interventions directed at preserving the integrity and function of beta-cells in the long term are less available. The use of some nutrients with important cellular protective roles that may lead to a preservation of beta-cells has not been fully tested; among these, zinc may be an interesting candidate. OBJECTIVE: To assess the potential of zinc supplementation as coadjuvant to diabetes therapy. METHODS: This article reviews the available information on the use of zinc as part of diabetes therapy. RESULTS: Cellular and animal models provide information on the insulin mimetic action of zinc, as well as its role as a regulator of oxidative stress, inflammation, apoptosis, and insulin secretion. Zinc supplementation studies in humans are limited, although some positive effects have been reported; mainly, a modest but significant reduction in fasting glucose and a trend to decreased glycated hemoglobin (HbA1c). CONCLUSIONS: Zinc supplementation may have beneficial effects on glycemic control. Nevertheless, among the studies considered, the vast majority lasted for 6 months or less, suggesting the importance of conducting long-duration studies given the characteristics of type 2 diabetes as a chronic disease.

[Vitamin D nutrition in Chilean pre-school children living in extreme latitudes]. / Estado nutricional de vitamina D en pre escolares chilenos de zonas australes.

BACKGROUND: Sunlight exposure is the main factor for adequate vitamin D (VitD) nutrition; in extreme latitudes there is an increased risk for its deficiency. AIM: To study VitD nutritional status in pre-school children living in austral latitudes of Chile. SUBJECTS AND METHODS: A blood sample was obtained from 60 pre-school healthy children (aged 2 to 5 years, 24 males), attending to public day-care centers in Coyhaique (45° 35' S), during March (time 1) and September (time 2). 250 HD, parathyroid hormone (PTH), calcium, phosphate and alkaline phosphatases (PA) were measured. Information about weather conditions during three months prior to the sample withdrawal was gathered. RESULTS: Forty nine percent of children had a normal weight and 11% were overweight. Vive children with unreliable 250 HD levels were excluded from analysis. At time 1, 250 HD levels were 21.6 ± 14.5 ngl mh (7.9-71.1). Sixty four percent of children had valúes < 20 ng/mL (deficiency). At time 2, the figures were 21.5 ± 13.2 ng/mL (9.4-68.5) and 67.3% of children were deficient. PTH, serum calcium, phosphate and PA were normal. Prior to time 1, the UVradiation Índex (UVI) was high to extreme (91.3%), with 3.3 and 73% of sunny and cloudy days, respectively. Mean minimal and maximal temperatures were 7 and 17.3°C respectively. Prior to time 2 the IUVwas low in 100%) of days; with 15.2 and 60.9 of sunny and cloudy days, respectively. Mean minimal and maximal temperatures were 0.3 and 6.7°C respectively. No association of 250 HD with the other metabolicparameters was found. CONCLUSIONS: Chilean pre-school children living in austral latitudes have a high rate of vitamin D deficiency, throughout the year, with no association with PTH, calcium, phosphate or PA. Further research is required to study vitamin D deficiency in other latitudes and magnitude of sunlight exposure.

Childhood Obesity and Plasma Micronutrient Deficit of Chilean Children between 4 and 14 Years Old.

OBJECTIVE: To analyze the nutritional status and plasma levels of vitamins and minerals in a cohort of Chilean children between 4 and 14 years old from three cities in Chile (Santiago, Antofagasta, and Concepcion). DESIGN: This is a descriptive analysis of micronutrient levels in Chilean children as it relates to obesity and food consumption. SETTING: This study included 1235 children from schools in Santiago (central area), Antofagasta (northern area), and Concepcion (southern area) in Chile. RESULTS: Plasma levels of micronutrients revealed deficiencies in children from all these cities. Copper (26.4%) and calcium (33.0%) deficiencies were found in the children from Antofagasta, whereas iron (26.7%) and zinc (20.8%) deficiencies were found in the children from Concepcion and Santiago, respectively. The percentage of children with vitamin D deficiencies was exceptionally high in all cities (over 78%). The analysis of micronutrients and nutritional status revealed that vitamin D deficiencies were significantly higher (p = 0.02) in overweight children, particularly in Antofagasta. In the analysis of the nutritional status of children and their food consumption habits, the proportion of overweight and obesity was significantly higher (p = 0.001) in children that skipped breakfast compared to children that did not. Finally, children from low socioeconomic levels were significantly more overweight and obese compared to children from high socioeconomic levels (p < 0.05). CONCLUSIONS: this is the first study to describe plasma levels of micronutrients in Chilean children and adolescents. High percentages of obesity, overweight, and vitamin D deficiency were detected in children. These results are of significant relevance to future public health policies in Chile.

Type 2 diabetic patients and their offspring show altered parameters of iron status, oxidative stress and genes related to mitochondrial activity.

Type 2 diabetes (T2D) is directly related to alterations in iron status, oxidative stress and decreased mitochondrial activity, but the possible interaction of these parameters among T2D patients and their offspring is unclear. The whole study included 301 subjects: 77 T2D patients and one of their offspring and 51 control subjects with one of their offspring. The offspring were older than 20 years old. We measured parameters of iron status (serum iron, ferritin and transferrin receptor), diabetes (pre and post-prandial glucose, insulin, lipids), oxidative stress (Heme oxygenase activity, TBARS, SOD, GSH, Vitamin E), as well as the expression of genes in blood leukocytes related to mitochondrial apopotosis (mitofusin and Bcl/Bax ratios). The offspring of T2D patients had increased levels of serum ferritin (P < 0.01) and lower transferrin receptor (P < 0.008); higher insulin (P < 0.03) and total and LDL cholesterol; higher heme oxygenase and SOD activities increased TBARS and lower GSH; decreased mitofusin and Bcl/Bax expression ratios compared to offspring of normal subjects. These results suggest that the offspring of T2D patients could have an increased metabolic risk of develop a cardiovascular disease mediated by oxidative stress and iron status.

CAG repeat polymorphism of androgen receptor gene and X-chromosome inactivation in daughters of women with polycystic ovary syndrome (PCOS): relationship with endocrine and metabolic parameters.

BACKGROUND: The polycystic ovary syndrome (PCOS) is a hyperandrogenic disorder that arise from a combination of genetic and environmental factors. AIM: To assess the role of the androgen receptor (AR) CAG repeat polymorphism in the metabolic and reproductive features in daughters of women with PCOS (PCOSd). METHODS: Sixty-seven PCOSd and 60 daughters of control women (Cd) were studied in early stages of sexual development. Sex steroids, glucose, insulin and lipids were determined. The AR CAG repeat sizes and X-chromosome inactivation (XCI) were analyzed. RESULTS: PCOSd and Cd had similar mean number of CAG repeats and XCI pattern. In PCOSd and Cd, methylation-weighted biallelic means CAGn (mwCAGn) was not associated with androgen levels. In infants and pubertal PCOSd, mwCAGn was associated with a low concentration of HDL-cholesterol. CONCLUSIONS: AR CAG repeat polymorphism appears to be unrelated with serum androgen levels. However, the short mwCAGn variant may have a possible impact on the lipid profile in PCOSd.

Polymorphisms in the interleukin-6 receptor gene (Asp358Ala) and body mass index in Chilean women with type 1 diabetes.

INTRODUCTION: Interleukin-6 receptor (IL6R) has been linked with type 2 diabetes and obesity. The presence of the Asp allele in Asp358Ala of IL6R has been linked with insulin resistance and weight gain. AIM: The aim of this study is to evaluate the frequency and the association of the Asp358Ala in the IL6R gene in Chilean women with type 1 diabetes (T1D) and its relationship with body mass index (BMI). PATIENTS AND METHODS: One hundred and forty-five patients with T1D (N = 145) and healthy control women (N = 103) were recruited. The polymorphisms were studied with polymerase chain reaction and restriction fragment length polymorphisms. The effect of the polymorphisms on BMI and age of diagnosis was evaluated. RESULTS: A higher frequency of the Asp allele was observed in patients with T1D compared with controls (0.483 vs. 0.364; p < 0.01). The Asp358Asp genotype was more prevalent in the T1D group compared with controls (0.152 vs. 0.097; p < 0.01). T1D patients younger than 19 years had a positive association of BMI-standard deviation scores with the Asp allele (p < 0.05). Finally, lower Glycated Hemoglobin 1c (HbA1c) levels were observed in patients carrying the Asp allele (p < 0.01). CONCLUSIONS: T1D in Chilean women appears to be associated with the presence of the Asp allele in IL6R. The IL6R polymorphism (Asp358/Asp) was associated with BMI in T1D patients. This genetic variant could have some role in weight gain in T1D women.

Frequency of MYO9B polymorphisms in celiac patients and controls.

INTRODUCTION: the MYO9B gene contributes to the maintenance of the intestinal barrier and it has been postulated as a risk factor of celiac disease (CD). The objective of this study was to compare the frequency and association rs2305764, rs2305767 and rs1457092 MYO09B polymorphisms in pediatric CD patients from and. PATIENTS AND METHODS: the study was made in 104 CD pediatric patients (Chilean and Argentineans) and 104 controls subjects. MYO9B gene polymorphisms were analyzed by Taqman allelic probes. We evaluated the Hardy-Weinberg equilibrium by means of Chi-square and compared the haplotypes distribution using Fisher test. RESULTS: SNPs rs2305767 and rs1457092 were associated with celiac disease (CD); TT genotype in rs2305767 would be a protective factor (p < 0.000, OR = 0.19 CI 0.1-0.4) and the CT genotype would be a risk factor (p < 0.0001, OR = 4.9 CI 2.2 to 11.3). CC genotype in rs1457092 also showed a protective effect for celiac (p < 0.000, OR = 0.07 CI 0.0 to 0.3). CONCLUSION: our findings suggest that genetic variation MYO9B gene is associated with CD, as a protective or a risk factor depending on the polymorphism studied.