Increased frequency of the rs2066853 variant of aryl hydrocarbon receptor gene in patients with acromegaly1. (17th March 2014)

• Record Type: Journal Article
• Authors: Cannavo, S.; Ferrau, F.; Ragonese, M.; Romeo, P. D.; Torre, M. L.; Puglisi, S.; De Menis, E.; Arnaldi, G.; Salpietro, C.; Cotta, O. R.; Albani, A.; Ruggeri, R. M.; Trimarchi, F.
• Is Part Of: Clinical endocrinology. Volume 81:Number 2(2014:Aug.)
• Page Start: 249
• Page End: 253
• Publication Date: 2014-03-17
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/cen.12424
• Languages: English
• ISSNs: 0300-0664

Abstract

<abstract abstract-type="main" id="cen12424-abs-0001"> <title>Summary</title> <sec id="cen12424-sec-0001" sec-type="section"> <title>Context</title> <p>Aryl hydrocarbon receptor (AHR) pathway has a key role in cellular detoxification mechanisms and seems implicated in tumorigenesis. Moreover, polymorphisms and mutations of AHR gene have been associated with several human and animal tumours. Although AHR has been found differently expressed in pituitary adenomas, AHR gene mutation status has never been investigated in acromegalic patients.</p> </sec> <sec id="cen12424-sec-0002" sec-type="section"> <title>Design</title> <p>In this study, we evaluated patients with apparently sporadic GH‐secreting pituitary adenoma for AHR gene variants.</p> </sec> <sec id="cen12424-sec-0003" sec-type="section"> <title>Patients and Methods</title> <p>Seventy patients with sporadic GH‐secreting pituitary adenoma (M = 27, age 59·1 ± 1·6 years) and 157 sex‐ and age‐matched controls were enrolled in the study. In all patients and controls, the exons 1, 2, 3, 5 and 10 of AHR gene were evaluated for nucleotide variants by sequencing analysis.</p> </sec> <sec id="cen12424-sec-0004" sec-type="section"> <title>Results</title> <p>The <italic>rs2066853</italic> polymorphism was identified in the exon 10 of 18/70 acromegalic patients and 9/157 healthy subjects (25·7 vs. 5·7%, χ<sup>2</sup> = 18·98 <italic>P </italic><<italic> </italic>0·0001), in homozygosis in one patient and in heterozygosis in the other 17 and in the 9 healthy subjects. Moreover, a heterozygous <italic>rs4986826</italic> variant in exon 10 was identified in a patient with heterozygous <italic>rs2066853</italic> polymorphism, and in the patient with homozygous <italic>rs2066853</italic> variant. This second polymorphism was not detected in the control group. Patients with rs2066853 polymorphism showed increased IGF‐1 ULN (<italic>P </italic><<italic> </italic>0·05) and prevalence of cavernous sinus invasion (<italic>P </italic>=<italic> </italic>0·05), thyroid (<italic>P </italic>= 0·02), bladder (<italic>P </italic>= 0·0001) or lymphohematopoietic (<italic>P</italic> <<italic> </italic>0·05) tumours.</p> </sec> <sec id="cen12424-sec-0005" sec-type="section"> <title>Conclusions</title> <p>AHR gene <italic>rs2066853</italic> polymorphism is significantly more frequent in acromegalic patients than in healthy subjects and is associated with increased disease aggressivity. Moreover, the <italic>rs4986826</italic> variant was detected in few patients with <italic>rs2066853</italic> polymorphism, but its role is to be cleared.</p> </sec> </abstract>