Sex-dependent relationship of C-reactive protein levels with HDL-cholesterol and HDL-phospholipid concentrations in children

Obesity has been consistently associated with inflammation but the influence of HDL on this association remains under study. Our study analyzes the influence of obesity-related parameters in the relationship of high-sensitivity C-reactive protein (hs-CRP) with HDL-cholesterol and HDL-phospholipid in male and female adolescents. The study sample population comprised 350 males and 401 females aged 12 to 16 years. Information regarding anthropometric parameters, HDL-cholesterol, HDL-phospholipid, adiponectin, leptin, insulin, and hs-CRP concentrations was available. hs-CRP levels were inversely related to HDL-cholesterol and HDL-phospholipid in males but not in females, and were positively related to leptin concentrations in both sexes but were not related to adiponectin levels. In regression analyses, HDL-phospholipid and leptin appeared significantly associated to hs-CRP in males in a model explaining 14.3% of hs-CRP variation. In females, only leptin appeared related to hs-CRP concentrations. After adjusting by leptin and adiponectin, males in the highest hs-CRP tertile showed significantly lower levels of HDL-cholesterol and HDL-phospholipid than those in tertiles 1 and 2, while no significant differences in HDL-cholesterol and HDL-phospholipid concentrations by hs-CRP tertile were observed in females. In summary, high hs-CRP levels were associated with lower plasma HDL-cholesterol and HDL-phospholipid concentrations in male adolescents irrespective of adipokines, while in females, HDL-related parameters are not associated with hs-CRP concentrationsTis research was funded by the Fondo de Investigación Sanitaria, Grant Number PI 18/01016, and by Biobank Grant Number FEDERRD09/0076/00101. Claudia Vales-Villamarín is recipient of a research contract from Carlos III Institute of Health (pFIS).Te article is dedicated to the late Prof. Manuel de Oya as the warmest homage to his memor

Differential effects of ethanol ingestion on somatostatin content,somatostatin receptors and adenylyl cyclase activity in thefrontoparietal cortex of virgin and parturient rats

Chronic ethanol ingestion decreases the number of somatostatin (SRIF) receptors in the rat frontoparietal cortex and female sex hormones modulate the effects of ethanol in the brain. Therefore, we investigated the differential effects of ethanol consumption on the SRIFergic system in the frontoparietal cortex of virgin and parturient rats given ethanol in their drinking water before and during gestation. In parturient rats, ethanol consumption decreased the density of SRIF receptors (25%, p < 0.01 vs control parturient group) whereas the SRIF-like immunoreactivity (SRIF-LI) content was increased (140%, p < 0.01). In virgin rats, ethanol ingestion decreased the density of SRIF receptors (42%, p < 0.01) more than in alcoholic parturient rats. SRIF-LI levels were unaffected. The inhibitory effect of SRIF on basal and forskolin-stimulated adenylyl cyclase was significantly lower in alcoholic virgin rats as compared to alcoholic parturient rats. No differences in the levels of the G inhibitory (Gi) ¿1 and Gi¿2 proteins were observed among the experimental groups. These results suggest that gestation may confer partial resistance to the ethanol-induced effect on the SRIFergic system

The influence of puberty on vitamin D status in obese children and the possible relation between vitamin D deficiency and insulin resistance

Background: Puberty can affect vitamin D levels. Objectives: The goal of this study was to analyze the relation between vitamin D deficiency and puberty in obese Spanish children, along with the possible interrelation between vitamin D status and degree of insulin resistance. Methods: A cross-sectional study was carried out, in which clinical and biochemical data were gathered from 120 obese and 50 normal weight children between January 2011 and January 2013. Results: Mean vitamin D levels were 19.5 and 31.6 ng/mL in obese pubertal and obese prepubertal children, respectively. About 75% of the obese pubertal subjects and 46% of the obese prepubertal subjects had vitamin D deficiency. Vitamin D levels were significantly lower in pubescent subjects compared with pre-pubescent subjects in summer, fall, and winter. There was no apparent relation between vitamin D levels and homeostasis model assessment index for insulin resistence (expressed in standard deviation score for sex and Tanner stage) in either puberty or pre-puberty. Conclusion: Puberty may be a risk factor for the vitamin D deficiency commonly found in the obese child population. This deficiency is not associated with higher insulin resistance in obese pubertal children compared with obese prepubertal childre

Children with type 1 diabetes have elevated high-sensitivity C-reactive protein compared with a control group

Introduction Our objective was to compare high-sensitivity C-reactive protein (hsCRP) levels in children with type 1 diabetes, healthy controls, and children with obesity. Additionally, we aimed to analyze the association between hsCRP levels and glycemic control measured by glycohemoglobin A (HbA1c) and anthropometric and biochemical variables. Research design and methods We conducted a non-randomized descriptive study of children with type 1 diabetes matched for sex and age with a control group and group with obesity. We recorded anthropometric parameters and studied variables related to diabetes, blood pressure, lipid profile, and HbA1c. hsCRP was measured by ELISA. Results We included 49 children with type 1 diabetes, 46 controls, and 40 children with obesity. hsCRP levels were significantly higher in the group with type 1 diabetes compared with controls and nearly significantly lower than in the group comprising children with obesity. We found no correlation between hsCRP and HbA1c and characteristics of type 1 diabetes with the exception of albumin to creatinine ratio. Statistically significant association was found between hsCRP and body mass index (BMI) and waist circumference Z-score. Conclusions The higher hsCRP levels observed in children with type 1 diabetes compared with a control group with a similar BMI suggest a basal inflammatory state that could increase cardiovascular risk. The main factors related to hsCRP are BMI and waist circumference, so obesity prevention should be a priority when performing follow-up in children with type 1 diabetes.This work was supported by Fundación Familia Alons

Análisis del rendimiento de la secuenciación del exoma clínico en hipogonadismo hipogonadotropo congénito teniendo en cuenta el grado de alteración del olfato.

Introduction: Congenital hypogonadotropic hypogonadism (CHH) can present alone or in association with anosmia or other congenital malformations. More than 30 genes have been identified as being involved in the pathogenesis of CHH with different patterns of inheritance, and the increasing availability of next generation sequencing (NGS) has increased the diagnostic yield. Methods: We analysed the diagnostic yield of NGS in patients with CHH using the clinical exome filtered with virtual panels. We also assessed whether designing panels based on the presence/absence of microsmia increased the diagnostic yield. Results: The use of a 34-gene virtual panel confirmed the diagnosis of CHH in 5 out of 9 patients (55%). In 2 out of 9 (22%), the findings were inconclusive. Applying the presence/absence of microsmia criterion to choose genes for analysis did not improve the diagnostic yield. Conclusions: The approach to the genetic study of patients with CHH varies depending on the resources of each healthcare facility, so the sensitivity of testing may vary substantially depending on whether panels, clinical exome sequencing or whole exome sequencing (WES) are used. The analysis of every genes related to CHH regardless of the presence/absence of microsmia seems to be the best approach.Introducción: El hipogonadismo hipogonadotropo congénito (HHC) puede presentarse de manera aislada o acompñado de anosmia o de malformaciones congénitas. Más de 30 genes han sido implicados en la patogénesis de HHC; además, se han descrito varios patrones de herencia asociados a esta entidad. La creciente disponibilidad de técnicas de secuenciación masiva (NGS) ha permitido que aumente el rendimiento diagnóstico del estudio de esta patología. Pacientes y métodos: Evaluamos el rendimiento diagnóstico del estudio mediante NGS de pacientes con HHC, usando la secuenciación del exoma clínico filtrado por paneles virtuales. Además, se analizó si el diseño de estos paneles, basándose en la presencia/ausencia de microsmia/anosmia aumentaban este rendimiento diagnóstico. Resultados: Usando un panel virtual compuesto de 34 genes pudimos confirmar el diagnóstico de HHC en cinco de nueve pacientes (55%). En dos de nueve individuos (22%) estudiados se obtuvieron resultados no concluyentes. La ausencia/presencia de microsmia para la elección de genes a estudiar no mejora el rendimiento diagnóstico. Conclusiones: El abordaje del estudio genético de pacientes con HHC puede variar en función de las técnicas disponibles en cada centro, por lo que la sensibilidad del test utilizado variará, dependiendo si se utiliza secuenciación de paneles, exoma clínico o exoma completo. El análisis de todos los genes relacionados con HHC independientemente de la presencia/ausencia de microsmia pareciera el abordaje con mejor rendimiento.This study was supported by the Department of Genomic Medicine of the Universidad Autónoma de Madrid-Fundación Jiménez Díaz (file 081800)

Genetic diagnosis of X-linked dominant hypophosphatemic rickets in a cohort study: Tubular reabsorption of phosphate and 1,25(OH)2D serum levels are associated with PHEX mutation type

<p>Abstract</p> <p>Background</p> <p>Genetic Hypophosphatemic Rickets (HR) is a group of diseases characterized by renal phosphate wasting with inappropriately low or normal 1,25-dihydroxyvitamin D₃(1,25(OH)₂D) serum levels. The most common form of HR is X-linked dominant HR (XLHR) which is caused by inactivating mutations in the <it>PHEX </it>gene. The purpose of this study was to perform genetic diagnosis in a cohort of patients with clinical diagnosis of HR, to perform genotype-phenotype correlations of those patients and to compare our data with other HR cohort studies.</p> <p>Methods</p> <p>Forty three affected individuals from 36 non related families were analyzed. For the genetic analysis, the <it>PHEX </it>gene was sequenced in all of the patients and in 13 cases the study was complemented by mRNA sequencing and Multiple Ligation Probe Assay. For the genotype-phenotype correlation study, the clinical and biochemical phenotype of the patients was compared with the type of mutation, which was grouped into clearly deleterious or likely causative, using the Mann-Whitney and Fisher's exact test.</p> <p>Results</p> <p>Mutations in the <it>PHEX </it>gene were identified in all the patients thus confirming an XLHR. Thirty four different mutations were found distributed throughout the gene with higher density at the 3' end. The majority of the mutations were novel (69.4%), most of them resulted in a truncated PHEX protein (83.3%) and were family specific (88.9%). Tubular reabsorption of phosphate (TRP) and 1,25(OH)₂D serum levels were significantly lower in patients carrying clearly deleterious mutations than in patients carrying likely causative ones (61.39 ± 19.76 vs. 80.14 ± 8.80%, p = 0.028 and 40.93 ± 30.73 vs. 78.46 ± 36.27 pg/ml, p = 0.013).</p> <p>Conclusions</p> <p><it>PHEX </it>gene mutations were found in all the HR cases analyzed, which was in contrast with other cohort studies. Patients with clearly deleterious <it>PHEX </it>mutations had lower TRP and 1,25(OH)₂D levels suggesting that the <it>PHEX </it>type of mutation might predict the XLHR phenotype severity.</p

Implicaciones clínico-diagnósticas del péptido Ghrelin en la infancia

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid. Facultad de Medicina. Departamento de Pediatría. Fecha de lectura: 23 de Diciembre de 200

Sex-Dependent Mediation of Leptin in the Association of Perilipin Polymorphisms with BMI and Plasma Lipid Levels in Children

Variations in the perilipin (PLIN) gene have been suggested to be associated with obesity and its related alterations, but a different nutritional status seems to contribute to differences in these associations. In our study, we examined the association of several polymorphisms at the PLIN locus with obesity and lipid profile in children, and then analyzed the mediation of plasma leptin levels on these associations. The single-nucleotide polymorphisms (SNPs) rs894160, rs1052700, and rs2304795 in PLIN1, and rs35568725 in PLIN2, were analyzed by RT-PCR in 1264 children aged 6&ndash;8 years. Our results showed a contrasting association of PLIN1 rs1052700 with apolipoprotein (Apo) A-I levels in boys and girls, with genotype TT carriers showing significantly higher Apo A-I levels in boys and significantly lower Apo A-I levels in girls. Significant associations of the SNP PLIN2 rs35568725 with high-density lipoprotein cholesterol (HDL-cholesterol), Apo A-I, and non-esterified fatty acids (NEFA) were observed in boys but not in girls. The associations of the SNPs studied with body mass index (BMI), NEFA, and Apo A-I in boys and girls were different depending on leptin concentration. In conclusion, we describe the mediation of plasma leptin levels in the association of SNPs in PLIN1 and PLIN2 with BMI, Apo A-I, and NEFA. Different leptin levels by sex may contribute to explain the sex-dependent association of the PLIN SNPs with these variables