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Published on: January 7, 2016
Impact of polymorphisms of human beta-adrenergic receptor gene on changes in height during growth hormone treatment
Hisafumi Matsuoka1, Saika Iwama, Naoko Miura
1Department of Pediatrics, Tokyo Women's Medical University Daini Hospital, Nishiogu, Japan.
Insights
Genetic variations in beta-adrenergic receptors influence growth in short children undergoing growth hormone (GH) therapy. The beta2-adrenergic receptor gene polymorphism significantly impacts height changes and obesity index, unlike the beta3-adrenergic receptor gene.
Area of Science:
- Genetics
- Endocrinology
- Pediatrics
Background:
- Short stature in children is a clinical concern often managed with growth hormone (GH) therapy.
- Adrenergic receptors, specifically beta-adrenergic receptors, play roles in metabolic regulation and growth.
- Polymorphisms in adrenergic receptor genes may influence individual responses to GH treatment.
Purpose of the Study:
- To investigate beta-adrenergic receptor gene polymorphisms (beta2 and beta3) in short children.
- To evaluate the impact of these polymorphisms on height and obesity index changes during GH treatment.
Main Methods:
- Genotyping for beta2 (Gly16Arg) and beta3 (Trp64Arg) adrenergic receptor polymorphisms in 75 short children.
- Analysis of height standard deviation scores (SD) and obesity index changes over 5 years of GH treatment.
- Comparison of treatment responses based on different genotypes.
Main Results:
- Beta3-adrenergic receptor gene polymorphism (Trp64Arg) showed no significant effect on height or obesity index.
- Beta2-adrenergic receptor gene polymorphism (Gly16Arg) influenced height response: Argl6Arg and Glyl6Arg genotypes showed significant height increases, while Glyl6Gly did not.
- Children with Glyl6Gly genotype had a higher baseline obesity index, which decreased significantly during GH treatment.
Conclusions:
- The beta2-adrenergic receptor gene polymorphism significantly modulates growth rate and energy expenditure in short children receiving GH therapy.
- The beta3-adrenergic receptor gene polymorphism appears to have a limited role in this context.
- Genetic screening of beta2-adrenergic receptor polymorphisms could potentially personalize GH treatment strategies.
Abstract:
The aim of this study was to investigate the occurrence of polymorphisms of the beta-adrenergic receptor gene in short children and to evaluate the possible influence of the polymorphisms on changes in height and obesity index in response to GH treatment. Of the 75 children enrolled in the study, 40 completed at least 5 years of GH treatment. The genotype distribution of the beta2 and 3-adrenergic receptor polymorphisms in the study population did not differ significantly from those reported in non-obese subjects. There were no significant differences in the SD score for height at any given time-point between the group with and without the Trp64Arg mutation of the beta3-adrenergic receptor gene. In relation to the Glyl6Arg polymorphism of the beta2-adrenergic receptor gene, the mean SD score for height increased significantly during GH treatment in children with Argl6Arg and Glyl6Arg. In those with Glyl6Gly, the score did not show any significant increase during all 5 years of GH treatment. In both the groups with and without the Trp64Arg mutation, the changes in obesity index did not reach statistical significance at any time-point. Only children with Glyl6Gly had a significantly higher baseline mean obesity index than those with Glyl6Arg. The index also decreased markedly from 21.9% to 5.8% in these children during the first 4 years of GH treatment. Thus, when the impact of the polymorphisms of these two receptor genes was studied simultaneously, it appeared that only the beta2-adrenergic receptor polymorphism had an important role to play in modulating the regulation of growth rate and energy expenditure in short children.
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