The Growth Hormone Receptor Exon 3 Polymorphism is Not Associated with Height or Metabolic Traits in Healthy Young Adults

Context: The GHR polymorphisms contribution to the interindividual variability in prenatal and postnatal growth as well as to metabolic traits is controversial.

Objective: The aim of this study is to analyze the association of the GHRfl/d3 polymorphism with prenatal and postnatal growth and metabolic outcomes in adult life and to compare the genotype distribution in different populations.

Design: 385 community healthy subjects followed from birth to adult life (23-25years old) were grouped according to birth size: small-SGA (n=130, 62 males), appropriate-AGA (n=162, 75 males) and large for gestational age-LGA (n=93, 48 males). GHRfl/d3 genotype distribution and its potential association with anthropometric (at birth, childhood and adult life) and metabolic features (in adult life) were analyzed and compared with data obtained from a systematic review of GHRfl/d3 association studies (31 articles).

Results: The frequency of the GHR d3/d3 genotype was lower in the LGA (χ2 p=0.01); SGA and AGA subjects exhibited an increased chance of the d3/d3 genotype (OR=3.58; 95%CI: 1.55; 8.24) and (OR=2.39; 95%CI: 1.02; 5.62), respectively. Despite the different prevalence among different birth size groups, in adults, GHRfl/d3 genotype was not associated with height, plasma IGF1 levels or metabolic phenotype and cardiovascular risk. GHRfl/d3 genotype distributions in AGA, SGA and LGA groups were comparable with those found in subjects of European origin but not with those of Asian ancestry.

Conclusions: The GHRd3 genotype was negatively associated with birth size but it was not associated with adult height or weight, plasma IGF1, metabolic phenotype or any marker of increased cardiovascular risk in young adults.