FEATURES OF HEREDITARY APTITUDE TO THE DEVELOPMENT OF THE PITUITARY ADENOMA ACCORDING TO THE DATA OF THE UKRAINIAN NEURO-ENDOCRINOLOGICAL CENTERE
Keywords:acromegaly, pituitary adenoma, hereditary aptitude, genetic analysis
Hormone-active tumors (adenomas) of the pituitary gland of somato- (ST) and somatomatotropinomas (SMT), the clinical manifestations of which is acromegaly, belong to the class of rare (orphan) diseases. The development of the tumor is due to a complex multi-stage process, which is influenced by genetic, epigenetic and environmental factors, as well as the state of the central nervous system and the microenvironment of the tumor. In most cases, monoclonal GH-secreting pituitary tumors arise de novo as a result of sporadic mutations. Meanwhile, there are remain little studied about features of inheritance of sporadic pituitary adenoma. The aim of this study is to investigate the features of a hereditary predisposition to benign neoplasms of the pituitary gland. Materials and methods. Analysis of the family accumulation of diseases and a hereditary predisposition to acromegaly was carried out using a genetic examination of 30 patients with acromegaly, whose average age was (41.62 ± 2.71) years. To determine the direction of selection, we studied the data of obstetric history of women in post-reproductive age (more than 45 years) in 2106 healthy residents of Kharkov and 15 patients with acromegaly. Genealogical information was obtained by conventional methods using the questionnaire. The proband phenotype was evaluated according to the history of the disease, and when determining the phenotype of sick relatives, the questionnaire method and data from the proband case history were used. Genetic analysis was performed using sequential testing of monogenic Mendelian and polygenic (D. Falconer) inheritance models. An assessment of «population frequency» or «cumulative incidence» was conducted. The relative adaptability (w) and the selection coefficient (s) were calculated, while w was estimated as the product of fertility and survival, and s = 1 – w. The direction of selection was evaluated by the difference between the selection coefficients in the population and among patients (Δs = sпоп – sВЗ). Statistical processing of the results was performed using criteria F and χ2. Results. Genetic analysis determined the correspondence of acromegaly inheritance to the parameters of the D. Falconer polygenic model. The genetic component of the predisposition to the disease is 92.20 %. No effect of the degree of metization on the development of acromegaly was revealed. Risk factors for the development of acromegaly are hereditary burden of diseases of the skeletal system and various malignant neoplasms. There is a positive trend in the selection of acromegaly, which leads to an increase in the population of the frequency of genes of predisposition to this disease.
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