Ukrainian Journal of Perinatology and Pediatrics. 2023. 1(93): 64-68; doi 10.15574/PP.2023.93.64
Aryayev M. L., Senkivska L. I.
Odessa National Medical University, Ukrainе

For citation: Aryayev ML, Senkivska LI. (2023). GHR-exon 3 genetic polymorphism in children with growth hormone deficiency. Ukrainian Journal of Perinatology and Pediatrics. 1(93): 64-68; doi 10.15574/PP.2023.93.64.
Article received: Dec 27, 2022. Accepted for publication: Mar 13, 2023.

The effectiveness of the latest genetic technologies in advancing the diagnosis of growth hormone deficiency (GHD) and predicting growth response to recombinant human growth hormone (rHGh) therapy has been insufficiently studied. The genetic polymorphism of GHR-exon 3 has been considered as a possible predictor of growth response to replacement therapy, but the data obtained are contradictory.
Purpose – to identify allelic variants of the growth hormone receptor gene (GHR-exon 3) in children with GHD; to identify the relationship of genetic polymorphism with other potential clinical and auxological predictors of growth response.
Materials and methods. The study was conducted at the Odesa Regional Children’s Clinical Hospital of the Odesa Regional Council. The cohort of children with GHD included 92 children (69 boys and 23 girls). Genotyping of two alleles of GHR-exon 3 (d3 – exon 3 deletion; fl – full-length gene) was performed by the method of triprimer polymerase chain reaction. After determination of the GHR-exon 3 genotype (d3/d3; d3/fl; fl/fl), genetic data were coded based on the presence or absence of the d3 allele (d3-GHR, fl/fl-GHR, respectively).
Results. Differences in growth potential in children with GHD associated with the d3-GHR genotype compared to the fl/fl-GHR genotype were found. In children without prior treatment, the d3-GHR genotype is associated with higher rates of «growth at baseline (SDS)», «growth (SDS) – target growth (SDS)» and stimulates an additional increase in growth rate by 2.2 cm in the first year of therapy. The results of the second year of rHGh treatment did not reveal a similar pattern of growth response. Taking into account the genetic polymorphism of GHR-exon 3 increases the sensitivity and accuracy of the mathematical model for predicting the growth response to replacement therapy in children with GHD.
Conclusions. The d3-GHR genotype is associated with a better growth response in children with GHD in the first year of replacement therapy, but not in the second.
The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies.
No conflict of interests was declared by the authors.
Keywords: growth hormone deficiency, GHR-exon 3, children.
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