ECE2017 Guided Posters Pituitary (12 abstracts)
Resistance to somatostatin analogues is associated with GSTP1 gene methylation and AHR rs2066853 variant in acromegaly patients
Francesco Ferraù 1 , Petronilla Daniela Romeo 1 , Soraya Puglisi 1 , Marta Ragonese 1 , Federica Spagnolo 1 , Riccardo Ientile 2 , Isa Anna Maria Picerno 2 , Monica Currò 2 , Giuseppa Visalli 2 , Angela Alibrandi 3 & Salvatore Cannavò 4
1Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; 2Department of Biomedical Sciences, Dental Sciences and Morpho-functional Imaging, Messina, Italy; 3Department of Economics, Messina, Italy; 4Department of Human Pathology of Adulthood and Childhood, Messina, Italy.
Evidences suggest that environmental contaminants exposure and/or the impairment of intracellular xenobiotic metabolizing system could affect pituitary pathophysiology. Glutathione-S-transferase-P1 (GSTP1) gene encodes for an enzyme that is involved in cellular detoxification mechanisms. GSTP1 altered activity or expression has been reported in some tumours.
We aimed to assess the GSTP1 gene promoter methylation status in acromegaly patients and its contribution to their clinical features.
Seventy-seven WT AIP gene acromegaly patients (50 women) have been screened for germline AHR rs2066853 variant and GSTP1 promoter methylation. Epidemiologic, clinical, biochemical and radiological parameters at diagnosis have been compared after patients’ stratification according to GSTP1 methylation status and the presence of AHR rs2066853 variant. We also evaluated the response to somatostatin analogues (SSA) administered either before or after surgery in 71 cases.
Seventeen patients were found to carry AHR rs2066853 variant and 26 methylated GSTP1 (GSTP1met). GSTP1met patients showed a higher prevalence of diabetes mellitus (P=0.01), colonic polyps (P=0.05), and were more resistant to SSA (P=0.02) as compared to GSTP1 unmethylated patients (GSTP1unmet).
On the basis of GSTP1 methylation status and the presence of AHR rs2066853 variant, we identified four groups: group 1, 40 patients GSTP1unmet and AHR WT; group 2, 20 patients only GSTP1met; group 3, 12 patients carrying only AHR rs2066853 variant; group 4, five patients with both GSTP1 methylation and AHR rs2066853 variant. Group 1 patients were more sensitive to SSA than other groups (P=0.02). Patients of group 4 were more resistant to SSA (P=0.02) and showed higher GH (P=0.03) and IGF1 (P=0.04) levels and lower percentage of GH decrease (P=0.04) after SSA than other groups.
In conclusion, GSTP1 methylation and AHR rs2066853 variant associate with resistance to SSA in acromegaly patients.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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