Paulo V G H Amorim1, Isabella P P Grande1, Rafael L Batista2, Leticia F G Silveira3, Ane Caroline T B Freire4, Marcello D Bronstein4, Raquel S Jallad4, Ericka B Trarbach5. 1. Laboratorio de Endocrinologia Celular e Molecular, LIM25, Disciplina de Endocrinologia e Metabologia, Hospital das Clinicas, FMUSP, São Paulo, Brasil. 2. Divisao de Neurocirurgia Funcional, Instituto de Psiquiatria - IPq, Hospital das Clinicas, FMUSP, São Paulo, Brasil. 3. Departamento de Clínica Médica, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil; Laboratório de Hormônios e Genética Molecular, LIM42, Disciplina de Endocrinologia e Metabologia, Hospital das Clinicas, FMUSP, São Paulo, Brasil. 4. Unidade de Neuroendocrinologia, Disciplina de Endocrinologia e Metabologia, Hospital das Clinicas, FMUSP, São Paulo, Brasil. 5. Laboratorio de Endocrinologia Celular e Molecular, LIM25, Disciplina de Endocrinologia e Metabologia, Hospital das Clinicas, FMUSP, São Paulo, Brasil; Unidade de Neuroendocrinologia, Disciplina de Endocrinologia e Metabologia, Hospital das Clinicas, FMUSP, São Paulo, Brasil. Electronic address: ericka.trarbach@hc.fm.usp.br.
Abstract
OBJECTIVES: This study analyzed the KISS1 c.-145delA (rs5780218) promoter polymorphism in a cohort of patients with growth hormone secreting pituitary adenoma (somatotropinoma) and controls, to investigate its role in the incidence of acromegaly and to assess patient/tumor characteristics. Material and methods rs5780218 allelic and genotypic distributions were compared between 49 somatotropinoma patients and 167 healthy controls. rs5780218 was also assessed in relation to patient characteristics and tumor aggressiveness, as characterized by tumor invasion and resistance to conventional therapy. The relationship between KISS1 mRNA expression and the rs5780218 genotype was also assessed in available pituitary tumor samples. RESULTS: The homozygous -/- variant genotype was associated with high rates of somatotropinoma (P<0.01), but not with tumor invasiveness, patient characteristics or hormonal remission. KISS1 mRNA expression was much lower in somatotropinomas carrying the deleted allele than in homozygous wild type AA. CONCLUSIONS: In this pilot study, the rs5780218 promoter polymorphism was evaluated in pituitary adenoma, and showed a possible association with the incidence of somatotropinoma but not with tumor progression.
OBJECTIVES: This study analyzed the KISS1 c.-145delA (rs5780218) promoter polymorphism in a cohort of patients with growth hormone secreting pituitary adenoma (somatotropinoma) and controls, to investigate its role in the incidence of acromegaly and to assess patient/tumor characteristics. Material and methods rs5780218 allelic and genotypic distributions were compared between 49 somatotropinomapatients and 167 healthy controls. rs5780218 was also assessed in relation to patient characteristics and tumor aggressiveness, as characterized by tumor invasion and resistance to conventional therapy. The relationship between KISS1 mRNA expression and the rs5780218 genotype was also assessed in available pituitary tumor samples. RESULTS: The homozygous -/- variant genotype was associated with high rates of somatotropinoma (P<0.01), but not with tumor invasiveness, patient characteristics or hormonal remission. KISS1 mRNA expression was much lower in somatotropinomas carrying the deleted allele than in homozygous wild type AA. CONCLUSIONS: In this pilot study, the rs5780218 promoter polymorphism was evaluated in pituitary adenoma, and showed a possible association with the incidence of somatotropinoma but not with tumor progression.