Association between 14 bp insertion/deletion HLA-G functional polymorphism and insulin resistance in a cohort of Italian children with obesity.

BACKGROUND: The non-classical HLA-class I molecule-g (HLA-G) gene shows a deletion/insertion (del/ins) polymorphism of a 14-base-pair sequence (14 bp) in the exon 8 at the 3' untranslated region. The presence of the 14 bp insertion allele has been associated to lower soluble HLA-G protein production, a protein with anti-inflammatory activities. So far, no studies have investigated the relationship between HLA-G 14 bp del/ins polymorphism and metabolic features of obese children and adolescents. We aimed to assess if the HLA-G ins/del polymorphism, and in particular the HLA-G ins/ins genotype determining lower sHLA-G production, is associated to insulin resistance (evaluated by homeostasis model assessment [HOMA]) in a population of obese children. METHODS: We enrolled 574 obese children and adolescents. Anthropometric and laboratory data were collected. The white blood cell (WBC) count was evaluated as surrogate marker of inflammation. C-reactive protein (CRP) was available in 48 patients. HOMA was calculated. Patients were genotyped for the HLA-G del/ins polymorphism. RESULTS: Subjects carrying the HLA-G ins/ins genotype, presented with higher HOMA, WBC and CRP values, compared to del/ins and del/del genotypes (P ≤ 0.0009, ≤0.02 and ≤0.0001, respectively). Comparison of the regression line slopes, performed for HOMA and WBC on the basis of HLA-G genotypes, showed that subjects carrying the HLA-G ins/ins genotype presented with a stronger correlation between HOMA and WBC, compared to the other genotypes (Model r2 3.13%, P ≤ 0.006). CONCLUSIONS: We showed a strong association between HLA-G 14 bp ins/ins genotype and HOMA in obese children and adolescents. This association could be hypothetically modulated by subclinical inflammation.

Basal levels of 17-hydroxyprogesterone can distinguish children with isolated precocious pubarche.

BACKGROUND: Basal levels of androgens, in particular 17-hydroxyprogesterone (17OHP), are widely debated as predictors of non-classical congenital adrenal hyperplasia (NCCAH) among patients with precocious pubarche (PP). Many authors have recommended the use of adrenocorticotropic hormone (ACTH) stimulation test in children with PP. The aim of our study was to identify clinical and biochemical predictors of NCCAH in children with PP. METHODS: We conducted a prospective study of 92 patients with PP undergoing an ACTH stimulation test. We tested the association of basal clinical and biochemical parameters with NCCAH diagnosis. Patients were suspected to have NCCAH if their stimulated 17OHP plasma levels were >10 ng/mL. In these patients, the diagnosis was confirmed by genetic test. RESULTS: Seven (7.6%) patients resulted having NCCAH. The best basal biochemical predictor for NCCAH was 17OHP level >2 ng/mL. In fact, a basal 17OHP level >2 ng/mL had 100% (95% confidence interval (CI), 59.04-100) sensitivity and 93% (95% CI, 85.3-97.37) specificity. The area under the receiver-operating characteristic curve for 17OHP was 0.99 (95% CI, 0.98-1.007). CONCLUSIONS: Basal 17OHP cut-off of 2 ng/mL was very effective in predicting NCCAH among our patients with PP. Assay-specific cut-off would probably be the best strategy to avoid unnecessary ACTH test.

Non-Rapid Eye Movement Sleep Parasomnias and Migraine: A Role of Orexinergic Projections.

INTRODUCTION: Sleep and migraine share a common pathophysiological substrate, although the underlying mechanisms are unknown. The serotonergic and orexinergic systems are both involved in the regulation of sleep/wake cycle, and numerous studies show that both are involved in the migraine etiopathogenesis. These two systems are anatomically and functionally interconnected. Our hypothesis is that in migraine a dysfunction of orexinergic projections on the median raphe (MR) nuclei, interfering with serotonergic regulation, may cause Non-Rapid Eye Movement parasomnias, such as somnambulism. HYPOTHESIS/THEORY: Acting on the serotonergic neurons of the raphe nuclei, the dysfunction of orexinergic neurons would lead to a higher release of serotonin. The activation of serotonergic receptors located on the walls of large cerebral vessels would lead to abnormal vasodilatation and consequently increase transmural pressure. This process could activate the trigeminal nerve terminals that innervate vascular walls. As a consequence, there is activation of sensory nerve endings at the level of hard vessels in the meninges, with release of pro-inflammatory peptides (e.g., substance P and CGRP). Within this hypothetical frame, the released serotonin could also interact with trigeminovascular afferents to activate and/or facilitate the release of the neuropeptide at the level of the trigeminal ganglion. The dysregulation of the physiological negative feedback of serotonin on the orexinergic neurons, in turn, would contribute to an alteration of the whole system, altering the sleep-wake cycle. CONCLUSION: Serotonergic neurons of the MR nuclei receive an excitatory input from hypothalamic orexin/hypocretin neurons and reciprocally inhibit orexin/hypocretin neurons through the serotonin 1A receptor (or 5-HT1A receptor). Considering this complex system, if there is an alteration it may facilitate the pathophysiological mechanisms involved in the migraine, while it may produce at the same time an alteration of the sleep-wake rhythm, causing sleep disorders such as sleepwalking. Understanding the complex mechanisms underlying migraine and sleep disorders and how these mechanisms can interact with each other, it would be crucial to pave the way for new therapeutic strategies.

The Rorschach Test Evaluation in Chronic Childhood Migraine: A Preliminary Multicenter Case-Control Study.

OBJECT: About 1.2-3.2% of children at 7 years of age with increasing age up to 4-19% in adolescents are suffering from migraine without aura (MwA). The aim of the present study is investigating the personality style associated with children and adolescents affected by MwA, administrating the Rorschach test, and comparing with typical developing healthy controls (TD). METHODS: 137 patients (74 males), aged 7.3-17.4 years (mean age 11.4, SD 3.02 years), affected by MwA according to the IHs-3 criteria. The Rorschach variables were treated as numerical variables and statistically tested with t-Student's analysis. RESULTS: No statistical differences were found between the MwA and TD for age (p = 0.55), and gender (p = 0.804). From the comparison between the two samples, MwA group shows lower W responses (p < 0.001), good quality W responses (p < 0.001), high frequency of detailed responses (p < 0.001), the presence of even minor form of good quality responses (p < 0.001), increased presence of animals answers (A%) (p < 0.001), more frequent trivial answers (Ban%) (p < 0.001). DISCUSSION: Rorschach interpretation pinpointed many interesting and, perhaps, peculiar aspects in our MwA population such as a trend predisposition for: analytical reasoning rather than synthetic, ease/practicality rather than creativity, oppositionality rather than external adaptation to the environment that may be interpreted as effect of general maladaptivity.