title: Older individuals heterozygous for a growth hormone-releasing hormone receptor gene mutation are shorter than normal subjects.
abstract: Growth hormone (GH)-releasing hormone (GHRH) is the most important stimulus for GH secretion by the pituitary gland. Subjects homozygous for GHRH receptor (GHRHR) gene (GHRHR) inactivating mutations have severe GH deficiency, resulting in severe short stature if not treated. We previously reported that young adults heterozygous for the c.57+1G>A null GHRHR mutation (MUT/N) have reduced weight and body mass index (BMI) but normal stature. Here we have studied whether older MUT/N have an additional phenotype. In a cross-sectional study, we measured height, weight and blood pressure, and calculated BMI in two groups (young, 20-40 years of age) and old (60-80 years) of individuals heterozygous for the same GHRHR mutation, and compared with a large number of individuals of normal genotype residing in the same geographical area. Standard deviation score (SDS) of weight was lower, and BMI had a trend toward reduction in young heterozygous compared with young normals, without significant difference in stature. Conversely, SDS of height was lower in older heterozygous individuals than in controls, corresponding to a reduction of 4.2 cm. These data show a reduced stature in older subjects heterozygous for the c.57+1G>A GHRHR mutation, indicating different effects of heterozygosis through lifespan.
authors.affiliation: Department of Medicine, Federal University of Sergipe Aracaju, Sergipe, Brazil.
authors.forename: Manuel H
authors.initials: MH
authors.lastname: Aguiar-Oliveira
authors.affiliation: Department of Medicine, Federal University of Sergipe Aracaju, Sergipe, Brazil.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Cardoso-Filho
authors.affiliation: Department of Medicine, Federal University of Sergipe Aracaju, Sergipe, Brazil.
authors.forename: Rossana M C
authors.initials: RM
authors.lastname: Pereira
authors.affiliation: Department of Medicine, Federal University of Sergipe Aracaju, Sergipe, Brazil.
authors.forename: Carla R P
authors.initials: CR
authors.lastname: Oliveira
authors.affiliation: Department of Medicine, Federal University of Sergipe Aracaju, Sergipe, Brazil.
authors.forename: Anita H O
authors.initials: AH
authors.lastname: Souza
authors.affiliation: Department of Medicine, Federal University of Sergipe Aracaju, Sergipe, Brazil.
authors.forename: Elenilde G
authors.initials: EG
authors.lastname: Santos
authors.affiliation: Department of Medicine, Federal University of Sergipe Aracaju, Sergipe, Brazil.
authors.forename: Viviane C
authors.initials: VC
authors.lastname: Campos
authors.affiliation: Department of Medicine, Federal University of Sergipe Aracaju, Sergipe, Brazil.
authors.forename: Eugênia H O
authors.initials: EH
authors.lastname: Valença
authors.affiliation: Department of Medicine, Federal University of Sergipe Aracaju, Sergipe, Brazil.
authors.forename: Francielle T
authors.initials: FT
authors.lastname: de Oliveira
authors.affiliation: Department of Medicine, Federal University of Sergipe Aracaju, Sergipe, Brazil.
authors.forename: Luiz A
authors.initials: LA
authors.lastname: Oliveira-Neto
authors.affiliation: Department of Medicine, Federal University of Sergipe Aracaju, Sergipe, Brazil.
authors.forename: Miburge B
authors.initials: MB
authors.lastname: Gois-Junior
authors.affiliation: Department of Medicine, Federal University of Sergipe Aracaju, Sergipe, Brazil.
authors.forename: Alecia A
authors.initials: AA
authors.lastname: Oliveira-Santos
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, The Johns Hopkins University School of Medicine (R.S), Baltimore, MD, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Salvatori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001827:Body Height / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D018013:Receptors, Neuropeptide / Q000235:genetics*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics*; D055815:Young Adult
chemical_list: D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; C048250:somatotropin releasing hormone receptor