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Effect of summer daylight exposure and genetic background on growth in growth hormone-deficient children.

ABSTRACT: The response to growth hormone in humans is dependent on phenotypic, genetic and environmental factors. The present study in children with growth hormone deficiency (GHD) collected worldwide characterised gene-environment interactions on growth response to recombinant human growth hormone (r-hGH). Growth responses in children are linked to latitude, and we found that a correlate of latitude, summer daylight exposure (SDE), was a key environmental factor related to growth response to r-hGH. In turn growth response was determined by an interaction between both SDE and genes known to affect growth response to r-hGH. In addition, analysis of associated networks of gene expression implicated a role for circadian clock pathways and specifically the developmental transcription factor NANOG. This work provides the first observation of gene-environment interactions in children treated with r-hGH.

SUBMITTER: De Leonibus C

PROVIDER: S-EPMC5223086 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Effect of summer daylight exposure and genetic background on growth in growth hormone-deficient children.

De Leonibus C C Chatelain P P Knight C C Clayton P P Stevens A A

The pharmacogenomics journal 20151027 6

The response to growth hormone in humans is dependent on phenotypic, genetic and environmental factors. The present study in children with growth hormone deficiency (GHD) collected worldwide characterised gene-environment interactions on growth response to recombinant human growth hormone (r-hGH). Growth responses in children are linked to latitude, and we found that a correlate of latitude, summer daylight exposure (SDE), was a key environmental factor related to growth response to r-hGH. In tu ...[more]

PMID: 26503811

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Project description:The prevalence of idiopathic oligozoospermia has been esteemed as high as 75%. An Italian survey has reported bilateral testicular hypotrophy in 14% of final-year high school students. The search for determinants of testicular growth in childhood is important for the primary prevention of spermatogenic failure. Therefore, this retrospective study aimed to evaluate the testicular growth and pubertal onset in deficient children treated recombinant human growth hormone (rhGH). To accomplish this, the clinical charts of 93 patients with GH deficiency (GHD) were carefully reviewed. Their mean age at the time of diagnosis was 11.2 ± 2.4 years. rhGH was administered for 44.0 ± 22.4 months, and the onset of puberty was recorded after a mean of 25.8 ± 22.4 months from the first rhGH administration. As expected, serum insulin-like growth factor 1 (IGF1) levels increased significantly after treatment. Before rhGH therapy, the Tanner stage was I in 59 out of 70 boys (84.3%), II in 8/70 (11.4%), III in 3/70 (4.3%). No one was on stage IV or V. The mean Tanner stage was 1.19 ± 0.51. At the last visit, the Tanner stage was I in 8/72 boys (11.1%), II in 6/72 (8.3%), III in 6/72 (8.3%), IV in 16/72 (22.2%), and V in 36/72 (50.0%). After a mean of 44.0 ± 22.4 months of rhGH treatment, the mean Tanner stage was 4.05 ± 1.30. Patients treated with rhGH showed a significant testicular volume (TV) growth over time, whereas no growth was observed in age-matched but not yet treated patients, even when the age was compatible with a spontaneous start of puberty. The multivariate regression analysis showed that the duration of treatment and the mean rhGH dose significantly predicted the percentage of TV increase. In contrast, age, serum FSH, and IGF1 levels, and final rhGH dose did not impact TV growth over time. In conclusion, these findings suggest that GH may play a role in testicular growth and pubertal onset, despite the descriptive nature of this study. Further properly designed studies are needed to confirm these findings. This knowledge may be useful to implement the diagnostic-therapeutic algorithm in case of a lack of testicular growth in childhood.

Project description:BackgroundQuantifying the association between adherence and the growth response to growth hormone (GH) treatment is hampered by suboptimal methods of measuring adherence, confounders associated with the growth response, and restriction of the outcome parameters to yearly growth velocities.AimTo investigate the effect of adherence on the two-year growth response to GH treatment in prepubertal children with idiopathic isolated growth hormone deficiency (GHD) participating in the easypod connect observational study (ECOS), a 5-year, Phase IV open-label study to continuously assess real-world adherence via the easypod electronic drug-delivery device.Patients and methodsOutcome measures were change in height standard deviation score (?HSDS), index of responsiveness (IoR), and parameters of two catch-up growth (CUG) curve functions (monomolecular growth curve and second degree polynomial) with adj-HSDS (HSDS minus Target height (TH) SDS) as dependent variable. Inclusion criteria were GHD, naïve to GH treatment, known TH, age <10y in girls and <12y in boys, ?3 measurements, HSDS <-2 at start, complete data on growth and adherence in the first and second year. Linear regression analyses were performed to test the association between adherence (continuous and high vs. low) and the outcome measures, also adjusted for potential clinical confounders (age at start, adj-HSDS at start, birth weight SDS, gestational age (<37 weeks vs ?37 weeks), GH dose, GH max (n = 58)). The formula of IoR already adjusts for confounders.ResultsIn total, 95 patients complied with the inclusion criteria. The strongest associations were found between high adherence in the second year (?91% as cut-off value) and IoR 2y (+0.62), and average adherence and high adherence (?78%) in the first two years and ?HSDS 0-2y (+0.11 SD per 1 injection/week, and +0.34 SD for high vs. low adherence).ConclusionSuboptimal adherence negatively affected the growth response in the first two years of GH treatment.

Dataset Information

Effect of summer daylight exposure and genetic background on growth in growth hormone-deficient children.

Publications

Effect of summer daylight exposure and genetic background on growth in growth hormone-deficient children.

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