The Exon 3-Deleted/Full-Length Growth Hormone Receptor Polymorphism and Response to Growth Hormone Therapy in Growth Hormone Deficiency and Turner Syndrome: A Multicenter Study

Abstract

Background/Aim: The exon 3-deleted/full-length (d3/fl) growth hormone (GH) receptor (GHR) polymorphism has been associated with responsiveness to GH therapy in some diagnostic groups. However, there are still controversies on this issue. To evaluate the effect of the GHR exon 3 polymorphism on growth after 1 and 2 years of GH therapy in Turkish patients with GH deficiency (GHD) and Turner’s syndrome (TS) and the distribution of GHR exon 3 isoforms. Materials and Methods: 218 patients with GHD (125 males/93 females) and 43 patients with TS were included in the study. The control group included 477 healthy adults aged from 18 to 57 years (54 females/423 males). Anthropometric parameters and insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 were evaluated annually. GHR isoforms were studied using simple multiplex PCR. Height and body mass index were expressed as standard deviation score (SDS). Results: There were no differences among TS, GHD and healthy adults regarding the distribution of GHR exon 3 isoforms (fl/fl, fl/d3 and d3/d3). There was a significant increase in height SDS in both diagnostic groups on GH therapy; however, there were neither differences in height SDS and Δheight velocity between fl/fl, fl/d3 and d3/d3 groups nor a correlation between the distribution of GHR exon 3 isoforms and change in IGF-1 SDS and IGFBP-3 SDS levels on GH therapy in either of the diagnostic groups. There was also no gender difference in GHR isoforms in healthy adults. Conclusion: The results suggest that responsiveness to GH therapy does not depend on the exon 3 GHR genotypes in GHD and TS patients.

Turner syndrome and genetic polymorphism: a systematic review

“…Four studies have investigated this SNP alone 15,17,19 and three, its role alone and in combination with polymorphisms in the VDR (vitamin D receptor), IGFBP3 (insulin-like growth factor binding protein) and SOCS2 (suppressor of cytokine signaling) genes, via gene-gene interaction. Three possible genotypes can be observed: fl/fl, fl/d3 and d3/d3, with the latter being the one with the lowest frequency.…”

“…20,21 One of the studies 20 mentioned that the possible reasons for the lack of correlation in two previous studies included the small number of patients evaluated 18 and the fact that few individuals are carriers of the d3 allele. 17,20 One way to increase sample size is to perform multicenter studies, such as those carried out by Ko et al 17 and Baş et al, 19 both retrospective. 17 The three studies that showed negative association of the d3-GHR polymorphism were carried out in Korea, Venezuela and Turkey.…”

TRANSITION IN ENDOCRINOLOGY: Treatment of Turner's syndrome during transition

“…During the last decade many studies showed growth hormone (GH) treatment as safe and effective for growth promotion in TS. Table 2 presents the results of growth therapy and indicates positive, negative and neutral determinants of therapy effectiveness as well as consequences and side effects of hormonal therapy in the analysed articles (4,5,7,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50).…”

Optimizing growth hormone threapy in chilhood growth hormone defiency

“…Örneğin, BH reseptorü ekzon 3 delesyon polimorfizmi (32,33) veya IGFBP-3 promotor geni -202 A polimorfizminin (34) özellikle ağır BHE vakalarında BH tedavi yanıtını artırabileceği öne sürülmektedir. Bu konunun ayrıntıları bu derlemenin kapsamı dışın-da olup, bu konuda çalışmalar devam etmektedir (35) .…”