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Napolioni V.,Innovation Pole for Genomics | Murray D.R.,University of California at Los Angeles | Comings D.E.,City of Hope National Medical Center | Peters W.R.,Loma Linda University | Gade-Andavolu R.,Desert Research Institute
Infection, Genetics and Evolution | Year: 2014

In geographical regions characterized by high pathogen prevalence, it has been shown that human populations tend to be characterized by lower levels of extraversion (E) and openness to experience (OtE). According to the "behavioral immune system" hypothesis, the reduction of extraversion and openness levels represents a behavioral defense against infections. Like the 'classical' immune system, the "behavioral immune system" could also be shaped by its underlying genetic background. Previous studies have shown that the *C allele of the ACP1 gene confers increased susceptibility to infectious/parasitic diseases. We hypothesized that carriers of the ACP1*C allele should likewise be associated with reduced E and OtE. We tested this hypothesis using two samples comprised of 153 students from Southern California (Group 1), and 162 female subjects recruited from an executive health program (Group 2), genotyped for ACP1 polymorphism and evaluated by the NEO Five-Factor Inventory (NEO-FFI). ACP1 was significantly associated with E: we found that carriers of ACP1*C showed reduced scores for E (Group 1: β= -4.263, P= 0.027; Group 2: β= -8.315, P= 0.003; Group 1. +. Group 2: β= -5.366, P= 0.001). Across groups, ACP1 was only marginally associated with OtE. In conclusion, the present study found that the ACP1*C allele, previously associated with an increased vulnerability to infectious/parasitic diseases may also be able to shape behavioral immune defenses by interaction with the level of E. © 2014 Elsevier B.V. Source

Napolioni V.,Innovation Pole for Genomics | Serone E.,University of LAquila | Iacoacci V.,University of Rome Tor Vergata | Carpi F.M.,Innovation Pole for Genomics | And 2 more authors.
Gene | Year: 2014

The dysregulation of both immune and inflammatory responses occurring with aging is believed to substantially contribute to morbidity and mortality in humans. We have already reported the association of the functional Variable Number of Tandem Repeat (VNTR) at the Immunoglobulin heavy chain (. IGH) enhancer HS1.2 with Immunoglobulin levels and with several autoimmune diseases. Herein we tested the association of the VNTR at the HS1.2 enhancer with human longevity, also evaluating the possible modulatory effect of TNFA promoter diplotype (rs361525/rs1800629). HS1.2 enhancer genotypes have been determined for 193 unrelated healthy individuals from Central Italy divided into two groups: Group 1 (18-84. yrs, mean age 56.8. ±. 19.4) and Group 2 (85-100. yrs, mean age 93.0. ±. 3.5). Homozygous subjects for *2 allele were significantly disadvantaged in reaching higher life-expectancy (OR. =. 0.457, p. =. 0.021). A significant interaction between TNFA promoter diplotype status, HS1.2 2/2 genotype and the two Groups was found (p. =. 0.014). Of note, TNFA -. 308A allele seems to exert a protective effect in HS1.2 2/2 carriers. These results support the hypothesis of an important role of HS1.2 VNTR in the puzzle of the immune-system regulation, evidenced also by the potential interaction with TNFA. Moreover, the previous results showing the association of HS1.2 *2 allele with inflammatory phenomena are consistent with the hypothesis that this allele is a detrimental factor in reaching advanced age. © 2014 Elsevier B.V.All rights reserved. Source

Prontera P.,University of Perugia | Serino D.,Ospedale Pediatrico Bambino Gesu | Caldini B.,University of Perugia | Scarponi L.,University of Perugia | And 7 more authors.
Journal of Autism and Developmental Disorders | Year: 2014

The duplication of the Williams–Beuren syndrome (WBS) region (7q11.23) is a copy number variant associated with autism spectrum disorder (ASD). One of the most intriguing aspects is that the reciprocal microdeletion causes WBS, characterized by hypersociability, marked empathy, and a relative capacity in verbal shortterm memory and language. Herein, we studied, by using functional morphological and volumetric magnetic resonance, a 17-year-old male patient who displays a de novo 7q11.23 duplication and ASD. The limbic system of the patient appeared hypo-functional, while the total brain volume was increased, thus contrasting, in an opposite and intriguing manner, with the global brain volume reduction reported in WBS. Even if these findings come from the analysis of a single patient and, therefore, have to be considered preliminary results, they encourage carrying on further functional and volumetric studies in patients with 7q11.23 duplication, to fully elucidate the role of this genedosage alteration on brain development and limbic system function. © Springer Science+Business Media New York 2014. Source

Concetti F.,I.R.C.C.S Neuromed | Carpi F.M.,University of Camerino | Nabissi M.,University of Camerino | Picciolini M.,Innovation Pole for Genomics | And 2 more authors.
European Journal of Human Genetics | Year: 2015

Recent evidence demonstrated a relevant role of adenosine deaminase (ADA) in replicative senescence of T cells through its capacity to modulate telomerase activity (TA). Herein, we tested the impact of the functional polymorphism ADA rs73598374:G>A (c.22G>A, p.Asp8Asn) on telomere biology, by measuring TA and leukocyte telomere length (LTL) in healthy subjects selected according to rs73598374 genotype. rs73598374-A carriers showed lower TA (P = 0.019) and shorter LTL (P = 0.003), respectively, compared to G/G carriers. rs73598374-A carriers showed a stronger cross-sectional age reduction of LTL (r = -0.314, P = 0.005) compared to G/G carriers (r = -0.243, P = 0.022). The reduced ADA activity associated to rs73598374-A variant predisposes those carriers to display higher levels of adenosine compared to G/G carriers. Consequently, it may lead to an accelerated process of replicative senescence, causing a stronger reduction of TA and in turn shorter LTL. In conclusion, the crucial role played by replicative senescence of the immune system in several human diseases and in the aging process underscores the relevance of the present findings and also spurs interest into the possible involvement of rs73598374 in shaping the susceptibility to several age-related diseases. © 2015 Macmillan Publishers Limited All rights reserved. Source

Prontera P.,University of Perugia | Napolioni V.,Innovation Pole for Genomics | Ottaviani V.,University of Perugia | Rogaia D.,University of Perugia | And 10 more authors.
Neurogenetics | Year: 2014

Gilles de la Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple motor and vocal tics, frequently associated with psychiatric co-morbidities. Despite the significant level of heritability, the genetic architecture of TS still remains elusive. Herein, we investigated an Italian family where an 8-year-old boy, his father, and paternal uncle have a diagnosis of TS. Array-CGH and high resolution SNP-array analyses revealed a heterozygous microdeletion of ∼135 kb at the 7q36.2 locus in the proband and his father. Fluorescent in situ hybridization and quantitative PCR (qPCR) analyses confirmed the presence of the alteration also in the paternal uncle. The deletion selectively involves the first exon of the DPP6 gene, leading to a down-regulation of its expression, as demonstrated by the reduced messenger RNA (mRNA) levels assessed by RT-qPCR. The DPP6 gene encodes for a type II membrane glycoprotein expressed predominantly in the central nervous system. To date, a de novo DPP6 exonic duplication, of uncertain significance, was reported in one patient with TS. Moreover, the DPP6 gene has been implicated in the pathogenesis of autism spectrum disorder (ASD) and, notably, in haloperidol-induced dyskinesia. This first familial case provides evidence for association between DPP6 haploinsufficiency and TS, further suggesting a plausible molecular link between TS and ASD, and might shed some light on the efficacy and tolerability profiles of antidopaminergic agents used for tic management, thus prompting further studies on a larger cohort of patients. © 2014, Springer-Verlag Berlin Heidelberg. Source

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