Older individuals heterozygous for a growth hormone-releasing hormone receptor gene mutation are shorter than normal subjects

Aguiar‐Oliveira, Manuel H.; Cardoso-Filho, Marco A; Pereira, Rossana M. C.; Oliveira, Carla R. P.; Souza, Anita H. O.; Santos, Elenilde G.; Campos, Viviane C.; Valença, Eugênia H O; Oliveira, Francielle T; Oliveira-Neto, Luiz A.; Gois-Junior, Miburge B; Oliveira-Santos, Alécia A; Salvatori, Roberto

doi:10.1038/jhg.2015.25

Cited by 4 publications

(4 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…308 Several studies inferred that the GHRHR SNPs rs17159772, rs4988494, rs2267721, rs4988498, and rs4988505 were associated with reduced human height, indicating that GHRHR might affect normal human height variation. 309–312 Furthermore, the phenotype of pituitary dwarfism was also observed in individuals with GHRHR mutations (IVS1 + 1G→A or IVS8+1G>A). 313–318 Harsloef et al and Torekov and colleagues reported that the GIPR polymorphism Glu354Gln (rs1800437) was associated with reduced human BMD and bone mass and increased fracture risk.…”

Section: Diseases or Dysfunction Caused By Gpcr Mutation Or Deletion mentioning

confidence: 96%

The role of GPCRs in bone diseases and dysfunctions

et al. 2019

View full text Add to dashboard Cite

The superfamily of G protein-coupled receptors (GPCRs) contains immense structural and functional diversity and mediates a myriad of biological processes upon activation by various extracellular signals. Critical roles of GPCRs have been established in bone development, remodeling, and disease. Multiple human GPCR mutations impair bone development or metabolism, resulting in osteopathologies. Here we summarize the disease phenotypes and dysfunctions caused by GPCR gene mutations in humans as well as by deletion in animals. To date, 92 receptors (5 glutamate family, 67 rhodopsin family, 5 adhesion, 4 frizzled/taste2 family, 5 secretin family, and 6 other 7TM receptors) have been associated with bone diseases and dysfunctions (36 in humans and 72 in animals). By analyzing data from these 92 GPCRs, we found that mutation or deletion of different individual GPCRs could induce similar bone diseases or dysfunctions, and the same individual GPCR mutation or deletion could induce different bone diseases or dysfunctions in different populations or animal models. Data from human diseases or dysfunctions identified 19 genes whose mutation was associated with human BMD: 9 genes each for human height and osteoporosis; 4 genes each for human osteoarthritis (OA) and fracture risk; and 2 genes each for adolescent idiopathic scoliosis (AIS), periodontitis, osteosarcoma growth, and tooth development. Reports from gene knockout animals found 40 GPCRs whose deficiency reduced bone mass, while deficiency of 22 GPCRs increased bone mass and BMD; deficiency of 8 GPCRs reduced body length, while 5 mice had reduced femur size upon GPCR deletion. Furthermore, deficiency in 6 GPCRs induced osteoporosis; 4 induced osteoarthritis; 3 delayed fracture healing; 3 reduced arthritis severity; and reduced bone strength, increased bone strength, and increased cortical thickness were each observed in 2 GPCR-deficiency models. The ever-expanding number of GPCR mutation-associated diseases warrants accelerated molecular analysis, population studies, and investigation of phenotype correlation with SNPs to elucidate GPCR function in human diseases.

show abstract

Section: Diseases or Dysfunction Caused By Gpcr Mutation Or Deletion mentioning

confidence: 96%

The role of GPCRs in bone diseases and dysfunctions

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In contrast, older HTZ individuals are in average 4.2 cm shorter than controls, showing ageassociated height reduction, possibly suggesting frailty, a public health problem. These data indicate different effects of heterozygosis through lifespan (80). Table 1 summarizes the principal findings in this IGHD group.…”

Section: Heterozygous (Htz) Phenotypementioning

confidence: 96%

“…These features have been published in 42 different publications (2,19,22,25,27,29,30,31,32,33,36,37,38,40,41,44,45,46,47,48,49,50,51,52,53,54,56,57,61,62,63,64,66,67,68,74,75,76,77,78,79,80). We have used this experiment of nature to discover 'usual laws of nature' as suggested by William Harvey, and to understand some aspects of more common conditions such as short stature, insulin resistance, diabetes, atherosclerosis, osteoporosis, cancer and ultimately longevity.…”

Section: Introductionmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: The multiple facets of GHRH/GH/IGF-I axis: lessons from lifetime, untreated, isolated GH deficiency due to a GHRH receptor gene mutation

Aguiar‐Oliveira

Souza

Oliveira

et al. 2017

European Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

Twenty years ago, we described kindred of 105 individuals with isolated GH deficiency (IGHD) in Itabaianinha County, in northeast Brazil, carrying a homozygous mutation in the GH-releasing hormone receptor gene. These subjects exhibit markedly reduced GH responsiveness to stimulatory tests, and anterior pituitary hypoplasia. Serum concentrations of IGF-I, IGF binding protein type 3 and the acid-labile subunit are markedly reduced, with a lesser reduction of IGF-II. The most striking physical findings of these IGHD individuals are the proportionate short stature, doll facies, high-pitched voice and visceral obesity with reduced fat-free mass. There is neither microphallus, nor neonatal hypoglycemia. Puberty is delayed, menopause anticipated, but fertility is preserved in both genders. The reduction in bone sizes is not even, with mean standard deviation scores for height of −7.2, total maxillary length of −6.5, total facial height of −4.3 and cephalic perimeter of −2.7. In addition, the non-osseous growth is not uniform, preserving some organs, like pancreas, liver, kidney, brain and eyes, and compromising others such as thyroid, heart, uterus and spleen. These subjects present higher prevalence of dizziness, mild high-tones sensorineural hearing loss, reduction of vascular retinal branching points, increase of optic disk, genu valgum and increased systolic blood pressure. Biochemically, they have high low density lipoprotein cholesterol and C-reactive protein levels, but maintain increased insulin sensitivity, and do not show premature atherosclerosis. Finally, they have normal immune function, and normal longevity. This review details the findings and summarizes 20 years of clinical research carried out in this unique population.

show abstract

“…Of these neighbors, two or three were sorted and contacted. If they fit the eligibility criteria, presenting normal homozygous wild‐type GHRHR allele according with our data banking with genotyped individuals from this community, and matched characteristics (age, sex, socioeconomic condition assessed by monthly income, diabetes, and smoking status), they were invited to participate in the study as a control group. All participants were informed of the nature and potential risks of their participation, and all signed a term of informed consent.…”

Section: Methodsmentioning

confidence: 99%