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J Clin Endocrinol Metab

Title:		Acromegaly Is More Severe in Patients With AHR or AIP Gene Variants Living in Highly Polluted Areas
Author(s):		Cannavo S; Ragonese M; Puglisi S; Romeo PD; Torre ML; Alibrandi A; Scaroni C; Occhi G; Ceccato F; Regazzo D; De Menis E; Sartorato P; Arnaldi G; Trementino L; Trimarchi F; Ferrau F;
Address:		"Department of Clinical and Experimental Medicine-Endocrinology Unit (S.C., M.R., S.P., P.D.R., M.L.T., F.T., F.F.), and Department of Economics (A.A.), University of Messina, 98100 Messina, Italy; Endocrinology Unit, Department of Medicine (C.S., G.O., F.C., D.R.), DIMED, University of Padua, 35128 Padua, Italy; Department of Internal Medicine (E.D., P.S.), General Hospital, 31044 Montebelluna, Italy; and Department of Endocrinology and Metabolic Diseases (G.A., L.T.), Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy"
Journal Title:		J Clin Endocrinol Metab
Year:		2016
Volume:		20160310
Issue:		4
Page Number:		1872 - 1879
DOI:		10.1210/jc.2015-4191
ISSN/ISBN:		1945-7197 (Electronic) 0021-972X (Linking)
Abstract:		"CONTEXT: An increased prevalence of acromegaly was found some years ago in a highly polluted area in North-Eastern Sicily, where high concentration of nonmethane hydrocarbons, volatile organic compounds, and cadmium was found. Aryl hydrocarbon receptor (AHR) pathway has a key role in detoxification of these compounds and in tumorigenesis. OBJECTIVE: We correlated the occurrence of AHR and/or AHR-interacting protein (AIP) gene variants with acromegaly severity according to pollution exposition. DESIGN, SETTING, AND PATIENTS: This was an observational, perspective study conducted over 7 years in four Italian referral centers for pituitary diseases in which 210 patients with acromegaly were enrolled between 2008 and 2015. INTERVENTION: Genetic screening of patients for AHR and AIP variants. MAIN OUTCOME MEASURES: Clinical, biochemical, and radiological data of patients with and without AIP and/or AHR gene variants, living in polluted (high-risk for health, [HR]) or nonpolluted (NP) areas of five Italian regions were evaluated and compared. RESULTS: Among the 23 patients from HR areas, nine showed AHR or AIP variants. Mean IGF-I levels and pituitary tumor diameter were significantly higher in these nine patients (HR/VAR+) than in the other 14 (HR/VAR-) and in the 187 from NP areas (44 NP/VAR+). Somatostatin analogs significantly decreased mean GH and IGF-I levels in patients from NP areas and in HR/VAR- (GH P < .05; IGF-I times the upper limit of normal P < .01) but not in HR/VAR+ group. CONCLUSIONS: Genetic variants potentially inducing functional abnormalities of the aryl hydrocarbon receptor (AHR) pathway are associated with a more severe acromegaly, increased pituitary tumor size, and somatostatin analog resistance in patients living in HR areas"
Keywords:		"Acromegaly/blood/*diagnosis/etiology/genetics Adult Aged Aged, 80 and over Environmental Pollution/*adverse effects Female Gene-Environment Interaction Genetic Variation Genotype Human Growth Hormone/blood Humans Insulin-Like Growth Factor I/metabolism In;"
Notes:		"MedlineCannavo, S Ragonese, M Puglisi, S Romeo, P D Torre, M L Alibrandi, A Scaroni, C Occhi, G Ceccato, F Regazzo, D De Menis, E Sartorato, P Arnaldi, G Trementino, L Trimarchi, F Ferrau, F eng Observational Study Research Support, Non-U.S. Gov't 2016/03/11 J Clin Endocrinol Metab. 2016 Apr; 101(4):1872-9. doi: 10.1210/jc.2015-4191. Epub 2016 Mar 10"