Endocrine Abstracts

Introduction: Growth rate tends to be greater in children living at higher latitudes although the underlying mechanisms are unclear. The aim of this study was to compare height velocity (HV) in response to recombinant human GH (r-hGH) therapy in children with GH deficiency (GHD) living at different latitudes.

Design: Pre-pubertal children with GHD (n=118) were enrolled from the PREDICT long-term follow-up prospective study (NCT00699855). Data were submitted from 28 centres in 14 countries. Ethnicity background was consistent with country of origin. Absolute latitude was that of the study site.

Methods: Patients were categorized into three groups based on latitude site: high (>75th percentile: ≥45 °), intermediate (25th–75th percentiles: 34–45 °) and low (<25th percentile: ≤34 °). To look at mechanisms related to latitude effect, the average number of daylight hours during summer at each centre was recorded. First year treatment (Y1) HV (cm/year) was assessed. The effect on HV of summer daylight exposure (SDE) and carriage/non-carriage of nine single nucleotide polymorphisms (SNPs) previously associated with high growth response was analyzed, within GRB10, IGFBP3, TGF-α, CYP19A1, SOS1, TP53 and INPPL1. The effect of SDE and SNP was assessed using a generalized linear model corrected for multiple variables: gender, baseline age, BMI, distance to target height, GH peak, r-hGH dose and birth weight.

Results: GHD patients from high latitudes had a better Y1 HV than from intermediate and low latitudes (median (Q1, Q3): 9.8 (8.5, 11.4) vs 8.0 (7.0, 9.7) and 8.0 (7.0, 10.5) cm/year, respectively; P=0.015). HV significantly correlated with SDE (r=0.256, P=0.006), but not with latitude (P>0.05). For seven growth-related SNPs within GRB10, IGFBP3, TGF-α, CYP19A1 and TP53, HV was significantly affected by an interaction between carriage of the SNP and SDE (P<0.05).

Conclusions: Growth response to r-hGH in GHD is influenced by both the carriage of specific growth-related SNPs and geographical location, which may be explained by daylight exposure.