RESUMEN
BACKGROUND: Disturbances in stress response mechanisms and hypothalamic-pituitary-adrenal axis (HPA) functioning are considered important factors involved in the pathophysiology of anorexia nervosa (AN). Thus, genetic variations in the end effector of HPA - glucocorticoid receptor gene and relationships to stressful life events (SLE) may be connected to a higher risk of illness. The aim of the study was examining the association between glucocorticoid receptor gene (NR3C1) polymorphisms and risk factors among stressful life events in AN patients. SUBJECTS AND METHODS: This study comprised 256 patients with AN and 167 control subjects. The questionnaires examining brief history of the mother's pregnancy and long-acting stress factors, as well as life events checklist to assess stressful life events during the 6 months prior to hospitalization were used. The eight common SNPs (rs6198, rs6191, rs6196, rs258813, rs33388, rs41423247, rs56149945 and rs10052957) of NR3C1 gene were genotyped. RESULTS: The association of five polymorphisms (rs6191, rs258813, rs33388, rs41423247 and rs10052957) and one complex allele (TCAGT) of NR3C1 gene with increased risk of AN were found. However, no significant correlations between early, long-acting and predicting hospitalization SLE and any of the analyzed polymorphisms were observed. CONCLUSIONS: The results confirm that the NR3C1 gene is associated with AN risk regardless of the type of stressful triggering factors.
Asunto(s)
Anorexia Nerviosa/genética , Acontecimientos que Cambian la Vida , Receptores de Glucocorticoides/genética , Adolescente , Adulto , Femenino , Humanos , Polonia , Polimorfismo Genético , Adulto JovenRESUMEN
In this research, we conducted a study of genes connected with the neurodevelopmental hypothesis of anorexia nervosa, using classical statistical and data-mining methods to establish a relationship with disease risk and algorithms to identify the best genetic predictors of anorexia nervosa.
Asunto(s)
Anorexia Nerviosa/genética , Árboles de Decisión , Adolescente , Algoritmos , Factor Neurotrófico Derivado del Encéfalo/genética , Bases de Datos Factuales/estadística & datos numéricos , Epistasis Genética , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Polimorfismo de Nucleótido Simple/genética , Proteínas Proto-Oncogénicas c-fyn/genética , Receptor trkB/genética , Análisis de Regresión , Adulto JovenRESUMEN
OBJECTIVES: Several lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays an important role in weight regulation and eating behaviors as well as in the activity-dependent neuroplasticity underlying learning and memory behaviors involving the hippocampus. In anorexia nervosa (AN) patients, abnormal serum BDNF concentrations, cognitive impairments and specific personality traits have been traditionally observed. This study explores the levels of four serum neurotrophins [BDNF, neurotrophin 3 (NTF3), neurotrophin 4 (NTF4) and glial cell line-derived neurotrophic factor (GDNF)] with respect to their use as potential biomarkers for AN. This study also investigates any associations that might exist between serum neurotrophin levels and neurocognitive impairment or personality traits. METHODS: Serum neurotrophin concentrations were measured in 60 AN patients (AN group) and 45 healthy controls (HC group). We correlated the serum levels of the four neurotrophins BDNF, NTF3, NTF4 and GDNF and the clinical type of anorexia. We also analyzed the relationship between serum neurotrophin levels and the Beck Depression Inventory, body mass index, executive functions by the Wisconsin Card Sorting test (WCST) and personality dimensions by the Temperament and Character Inventory (TCI) test. RESULTS: Serum NTF4 concentrations were significantly lower when comparing all AN patients (34.7 ± 72.5 pg/ml) or restriction type AN patients (29.1 ± 62.5 pg/ml) with the HC group (58.4 ± 135.8 pg/ml; p = 0.004 and p = 0.005, respectively). A significant correlation (p < 0.005) between BDNF serum levels and patient personality dimensions as measured by the TCI test was observed. Furthermore, significant correlations were observed between NTF4 and GDNF serum levels and executive function as measured by the WCST. CONCLUSIONS: These data suggest that NTF4 might serve as a biomarker for AN. Furthermore, BDNF and GDNF serum levels appear to be associated with personality traits and executive function.
