Growth Hormone Receptor Polymorphism Research Articles

The Role of the GH Receptor Polymorphisms as a Prognostic Factor of Vertebral Fractures in Acromegalic Patients Resistant to First-generation SSAs and Treated with Pegvisomant or Pasireotide LAR.

Acromegaly is associated with skeletal fragility and increased prevalence of vertebral fractures (VF). Two isoforms of GH receptor (GHR) have been described, which differ in the presence or absence of a transcript of exon 3 of the GHR gene. Both isoforms produce a functional receptor, but the exon 3-deleted isoforms (d3-GHR) have greater sensitivity to endogenous and recombinant GH than the full-length isoform (fl-GHR). We conducted a longitudinal, retrospective, observational, single-center study to investigate the role of GHR polymorphism as a prognostic factor of incidental VF (I-VF) in firstgeneration somatostatin analogs (fg-SSAs)-resistant acromegalic patients and treated with Pegvisomant or Pasireotide LAR. Seventy-two patients with active acromegaly were included: 28 patients carried the d3-GHR isoform, and 44 patients carried the fl-GHR isoform. Forty-six patients were treated with Pegvisomant in combination with fg-SSAs, and 26 were treated with Pasireotide LAR. At the last follow-up, 58 patients achieved biochemical control of acromegaly. Eighteen patients carried prevalent VF (P-VFs), while 14 patients experienced the occurrence of I-VFs. From the group treated with Pegvisomant in combination with fg-SSAs, 32 patients carried the fl-GHR isoform, and 14 carried the d3-GHR isoform. From the group treated with Pasireotide LAR, 12 patients had the fl-GHR isoform, and 14 patients carried the d3-GHR isoform. I-VF occurred more frequently in patients with the fl-GHR isoform compared to d3-GHR (p =0.04); otherwise, I-VF occurred more frequently in patients with the d3-GHR isoform than fl-GHR (p =0.01). The GHR polymorphisms could improve the therapeutic approach in acromegaly, tailored to the individual patient, in the context of personalized medicine.

GH receptor polymorphisms guide second-line therapies to prevent acromegaly skeletal fragility: preliminary results of a pilot study.

Skeletal fragility is characterized by increased frequency of vertebral fractures (VFs) in acromegaly. Several trials were conducted to identify modifiable risk factors and predictors of VFs, with limited data on the prognostic role of GH receptor (GHR) isoforms. In this study, we investigated the potential role of GHR polymorphism on the occurrence of incidental VFs (i-VFs), in patients treated with second-line medical therapies. A longitudinal, retrospective, observational study was conducted on a cohort of 45 acromegalic patients not-responsive to first-generation somatostatin receptor ligands (fg-SRLs) and treated with GHR antagonist (Pegvisomant) or with the second-generation SRLs (Pasireotide long-acting release). Second line treatments were Pegvisomant plus fg-SRLs in 26 patients and Pasireotide LAR in 19 patients. From the group treated with fg-SRLs+Peg-V, the fl-GHR isoform was identified in 18 patients (69.2%) and the d3-GHR isoform in 8 patients (30.8%). I-VFs arose exclusively in fl-GHR isoform carriers (p=0.039). From the group treated with Pasireotide LAR, the fl-GHR isoform was identified in 11 patients (57.9%), and the d3-GHR isoform in 8 patients (42.1%). I-VFs arose exclusively in d3-GHR isoform carriers (p=0.018). Patients with fl-GHR isoform had a higher risk for i-VFs if treated with fg-SRL+Peg-V (OR: 1.6 95%IC: 1.1-2.3, p=0.04), and a lower risk if treated with Pasi-LAR (OR: 0.26 IC95%: 0.11-0.66, p=0.038). Our data support a predictive role of the GHR isoforms for the occurrence of i-VFs in acromegalic patients treated with second-line drugs, tailored to the individual patient. The knowledge of the GHR polymorphism may facilitate the choice of second-line therapies, improving the therapeutic approach, in the context of personalized medicine.

THU050 The Role Of The GH Receptor Polymorphism As Prognostic Factor Of Vertebral Fractures In Acromegaly Patients Resistant To First Generation SSAs And Treated With GH Receptor Antagonist Or Second Generation Somatostatin Ligand

Abstract Disclosure: F. Costanza: None. S. Chiloiro: None. A. Giampietro: None. P. Mattogno: None. A. Infante: None. F. Angelini: None. L. Lauretti: None. A. Olivi: None. A. Pontecorvi: None. F. Doglietto: None. L. De Marinis: None. A. Bianchi: None. Acromegaly is associated with skeletal fragility and an increased prevalence of vertebral fractures (VF). In recent years several authors have tried to investigate the markers that can predict the risk of bone fragility in this endocrine disorder. Two different isoforms of the GH receptor (GHR) have been described so far, which differ in the presence or absence of a transcript of exon 3 of the GHR gene. Both isoforms produce a functional receptor, but the exon 3-deleted isoforms (d3-GHR) have greater sensitivity to endogenous and recombinant GH than the full-length isoform (fl-GHR). We conducted a longitudinal, retrospective, observational, single-center study of first-generation SSA-resistant acromegaly patients, with the aim of investigating the role of GHR polymorphism as a prognostic factor of incidental VF (I-VF) in first-generation SSA-resistant acromegalic patients and treated with GH receptor antagonist (Pegvisomant) or second-generation somatostatin ligand (Pasireotide Lar).72 patients with acromegaly were included. 28 patients carried d3-GHR isoform (38.9%) and 44 patients carried fl-GHR isoform (61.1%). At baseline, all patients were affected by active acromegaly; 46 patients were treated with Pegvisomant in combination with first generation SSA and 26 were treated with Pasireotide Lar. 18 patients (25%) carried P-VFs. At last follow-up, 58 patients achieved biochemical control of acromegaly (80.6%). 14 patients experienced the occurrence of I-VFs. From the group treated with Pegvisomant in combination with first generation SSA, 32 patients carried fl-GHR polymorphism and 14 carried d3-GHR polymorphism. At baseline, 10 patients (21.7%) were I-VF carriers. At follow-up, 8 patients developed P-VF (17.4%). I-VF occurred more frequently in patients carrying fl-GHR isoform compared to d3-GHR (p=0.04). From the group treated with Pasireotide Lar, 12 patients carried fl-GHR isoform and 14 patients carried d3-GHR isoform. At baseline, 8 patients (30.8%) were I-VF carriers. At follow-up, 6 patients developed P-VF (23.1%). I-VF occurred more frequently in patients carrying d3-GHR isoform than fl-GHR (p=0.01) and in patients with P-VF as compared to patients without P-VF (p=0.05).In conclusion, the GH receptor polymorphism could assume greater relevance as a prognostic factor of VF in acromegaly patients. In the future, the knowledge of the GHR polymorphism may improve the therapeutic approach of acromegaly patients, tailored to the individual patient, in the context of personalized medicine. Presentation: Thursday, June 15, 2023

The Role of the GH Receptor Polymorphism as Prognostic Factor of Vertebral Fractures in Acromegaly Patients Resistant to First Generation SSAs and Treated with GH Receptor Antagonist or Second-Generation Somatostatin Ligand

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

POLYMORPHISM OF GROWTH HORMONE RECEPTOR GENE AND MYOGENIC FACTOR 5 GENE IN DAIRY CATTLE POPULATIONS

Investigations of the genetic structure features of the populations of Ukrainian Black-and-White and Red-and-White dairy breeds by polymorphism of growth hormone receptor (GHR) and myogenic factor 5 (MYF5) genes were carried out. AluI-polymorphism in the promoter fragment of the GHR gene and TaqI-polymorphism in the second intron of the MYF5 gene was detected using polymerase chain reaction and restriction analysis (PCR-RFLP). According to the research results, it was shown that the growth hormone receptor and myogenic factor 5 genes in the populations of Ukrainian Black-and-White and Red-and-White dairy breeds are polymorphic. In the population of the Ukrainian Black-and-White dairy breed at the GHR locus, the frequency of the AluI+ allele was 0.61; allele AluI- – 0.39; at the MYF5 locus, the TaqI+ allele frequency was 0.65; allele Taq- – 0.35, respectively. In the population of the Ukrainian Red-and-White dairy breed at the GHR locus, the frequency of the AluI+ allele was 0.54; allele AluI- – 0.46; at the MYF5 locus, the TaqI+ allele frequency was 0.64; allele Taq- – 0.36, respectively. Both experimental populations for GHR and MYF5 loci are in a genetic equilibrium state according to Hardy-Weinberg, which indicates the absence of microevolutionary changes in the process of their reproduction. There were no significant fluctuations in the genetic structure according to the revealed features of the genotype and allele frequencies distribution. The breeding work that is carried out on both populations does not affect marker alleles (which are described in the work), which is reflected in the features of the genetic-population structure of the experimental groups and their equilibrium state. The features of the distribution of individuals with different genotypes by GHR and MYF5 loci in the populations of both breeds make it possible to carry out further studies to determine the relationship between the identified allelic variants of polymorphic loci with parameters of animal productivity.

A common deletion in the growth hormone receptor gene (d3-GHR) in the offspring is related to maternal placental GH levels during pregnancy

BackgroundA common growth hormone receptor polymorphism with deletion of exon 3 (d3-GHR) has previously been linked to increased postnatal growth on the one hand and decreased fetal growth on the other. Regulation of fetal growth is positively dependent on secretion of placental GH (hGH-V). ObjectiveWe explored the effect of the fetal d3-GHR genotype on maternal serum levels of hGH-V and fetal growth. The cellular localization of hGH-V synthesis and the GH receptors were determined in normal placentas. Methods43 healthy mother-child pairs were examined during pregnancy with measurements of hGH-V during third trimester, and serial ultrasound measurements determined fetal growth rate. Birth anthropometrics were obtained. The GHR genotype of the child was analysed postnatally. Immunohistochemical (IHC) analysis was conducted on four placentas. ResultsThe presence of the d3-GHR genotype was associated with a markedly reduced concentration of hGH-V in maternal serum (β −0.52, SE 0.24, p = 0.04) compared to those who had a fl/fl genotype. Accordingly, a tendency towards reduced fetal growth rate during third trimester (β −25.8, SE 12.7, p = 0.05) and a lower birth weight were found among carriers of the d3-GHR allele, but these associations did not reach statistical significance (p = 0.08). IHC analysis showed expression of placental GH and GHR in the villous syncytiotrophoblast, the extravillous trophoblast, and the decidual cells and smooth muscle cells in chorionic vessels. ConclusionsThe presence of the d3-GHR polymorphism in the fetus was associated with lower maternal serum levels of hGH-V, decreased fetal growth rate in third trimester and lower birth weight compared to the wildtype.

Association of GHR Polymorphisms with Milk Production in Buffaloes.

Simple SummaryThe present study reported two missense mutations in the buffalo GHR gene: A novel (c.380G>A) and (c.836T>A) which was described in previous studies. These two single nucleotide polymorphisms (SNPs) were found to be associated with milk yield, fat %, protein %, and 305 day-milk, fat and protein yield, with higher performance for AA haplotype animals. Therefore, selection of buffaloes with AA haplotype would more likely improve milk production traits. Consequently, this would allow breeders to take more precise selection decisions, leading to significantly higher productivity and profitability within the Egyptian buffalo herds.For its role in the mediation of growth hormone (GH) galactopoietic effect, growth hormone receptor (GHR) was considered a functional candidate gene for milk performance in cattle. However, its genetic variation and potential effect have not been investigated in Egyptian buffaloes. This study aimed to screen GHR for polymorphisms and study their associations with milk traits in Egyptian buffaloes. Polymerase chain reaction, single-strand conformation polymorphism, and sequencing were used to identify mutations in 4 exons (E4–E6 and E8) of the GHR gene in 400 Egyptian buffaloes. No polymorphisms were found in E4, while 2 SNPs (c.380G>A/p.Arg127Lys and c.387C>T/p.Gly129) in E5, one silent mutation (c.435A>G/p.Pro145) in E6, and another missense mutation (c.836T>A/p.Phe279Tyr) in E8 were detected. The c.380G>A SNP in the extracellular domain was associated with milk yield, fat %, protein %, and 305-day milk, fat and protein yield, with higher levels in animals carrying the mutant A allele. The c.836T>A SNP in the transmembrane domain was associated with milk yield, fat %, protein %, and 305-day milk, fat and protein yield, with higher milk yield and lower fat %, protein %, fat and protein yield in the mutant A allele-animals. Interestingly, animals with the two mutant AA alleles produced higher milk yield, fat %, protein %, fat and protein yield, accompanied with upregulated expressions of GHR, GH, insulin-like growth factor 1 (IGF1), prolactin (PRL), prolactin receptor (PRLR), β-casein (encoded by CSN2 gene), and diacylglycerol acyltransferase-1 (DGAT1) genes and proteins in milk somatic cells. Therefore, selection of Egyptian buffaloes with mutant AA haplotypes for the novel c.380G>A SNP and the well-known c.836T>A SNP could improve milk yield and quality in buffaloes.

Craniofacial Morphology in Children with Growth Hormone Deficiency and Turner Syndrome.

The review aims to collect and demonstrate recent knowledge about craniofacial morphology in growth hormone (GH)-deficient children and children with Turner syndrome. The review describes also the effects of growth hormone treatment on craniofacial morphology of children with growth hormone deficiency and Turner syndrome. Regardless of the disorder it accompanies, short stature is associated with similar craniofacial features characteristic of all short-statured children. Characteristic craniofacial features involve lesser dimensions of the cranial base and mandibular length, proportionately smaller posterior than anterior facial height, retrognathic face, and posterior rotation of the mandible. We also analyze orthodontic treatment in children affected by disorders associated with GH deficiency or provided with growth hormone treatment in the aspect of craniofacial growth. Recent publications show also the connection between growth hormone receptor polymorphism and craniofacial growth. Specialists and orthodontists treating short-statured children must be aware of the results of studies on craniofacial morphology and educate themselves on the topic of craniofacial growth in children with short stature. Moreover, knowledge of the influence of GH therapy on growth of craniofacial structures is necessary to decide the proper timing and planning of orthodontic treatment.

Personalized approach to growth hormone replacement in adults.

Growth hormone (GH) deficiency (GHD) in adults is well-characterized and includes abnormal body composition, reduced bone mass, an adverse cardiovascular risk profile, and impaired quality of life. In the early 1990s, it was also shown that patients with hypopituitarism without GH replacement therapy (GHRT) had excess mortality. Today, GHRT has been shown to decrease or reverse the negative effects of GHD. In addition, recent papers have shown that mortality and morbidity are approaching normal in hypopituitary patients with GHD who receive modern endocrine therapy including GHRT. Since the first dose-finding studies, it has been clear that efficacy and side effects differ substantially between patients. Many factors have been suggested as affecting responsiveness, such as sex, age, age at GHD onset, adherence, and GH receptor polymorphisms, with sex and sex steroid replacement having the greatest impact. Therefore, the individual tailoring of GH dose is of great importance to achieve sufficient efficacy without side effects. One group that stands out is women receiving oral estrogen replacement, who needs the highest dose. Serum insulin-like growth factor-1 (IGF-1) is still the most used biochemical biomarker for GH dose titration, although the best serum IGF-1 target is still debated. Patients with GHD due to acromegaly, Cushing's disease, or craniopharyngioma experience similar effects from GHRT as others. Arch Endocrinol Metab. 2019;63(6):592-600.

Current aspects of diagnosis and treatment of adult GH-deficiency

Adult growth hormone (GH) deficiency (AGHD) is a condition characterized by alterations in body composition, lipid and carbohydrate metabolism, bone mineral density and poor quality of life; however, clinical presentations of AGHD are mostly non-specific. Untreated AGHD is associated with increased cardiovascular morbidity and mortality. Stimulation tests are used for the diagnosis: insulin tolerance test, glucagon stimulation test, growth-hormone releasing hormone and arginine stimulation test. Moreover, in 2017 FDA approved the use of macimorelin (oral GH secretagogue) for the diagnosis of AGHD. In childhood GH-deficiency, apolipoprotein A-IV, CFHR4 (complement factor H-related protein 4) and PBP (platelet basic protein) were identified as potential biomarkers of the disease, however, this was not investigated in AGHD. GH treatment starts from the minimal dose, which allows minimizing the adverse effects. According to published meta-analyses, AGHD treatment generally does not lead to increased risk of malignancy and recurrence of sellar neoplasms in adult patients. Published data on GH receptor polymorphism associations with treatment efficacy remains controversial. Development of long-acting GH formulations is a currect perspective for the increase of treatment compliance.

SAT-050 Growth Hormone Receptor Polymorphism and Its Effects on Clinical and Biochemical Expression in Acromegalic Patients

Introduction: Acromegaly results from the chronic and persistent elevation of growth hormone (GH) circulating levels. Several isoforms of the receptor of GH have been identified; one contains exon 3 giving rise to the full form of the GHR or full-length (fl), and another one lacking this exon (d3). This isoform heterogeneity results in the following genotypes: homozygous fl, heterozygous d3/fl and homozygous d3. Objective: To determine if the GHR genotype influences the clinical and/or biochemical expression of acromegaly. Methods: Forty-nine (30 women/19 men) acromegalic patients and forty-one control subjects (22 women/19 men), aged 30 to 76 years, who attended the Endocrinology Department of a Hospital in Buenos Aires, Argentina, were evaluated. Genotyping of the GHR was performed by a multiplex polymerase chain reaction (GAP-PCR). Clinical data were recorded, and general biochemical and hormonal determinations were carried out (IGF-1, GH and PRL). To measure tumor dimension, Magnetic Resonance Imaging (MRI) of the sellar area was performed in all patients. Results: The frequency of the genotypes was 61.2% homozygous fl, 34.7 % heterozygous d3/fl and 4.1 % homozygous d3 in acromegalic patients and 48.8% homozygous fl, 41.5% heterozygous d3/fl and 9.7% homozygous d3 in control subjects. The frequency of the genotypes in the studied population was in Hardy-Weinberg equilibrium (p = 0.8878). In this group of acromegalic patients, we did not observe any associations of the genotypes with the body mass index (BMI), the presence of micro or macroadenomas, the response to treatment, the presence of hypertension, diabetes or dyslipidaemia, neither with GH, IGF-1 or PRL levels. Conclusion: The present study confirms that the distribution of the allele coding for the isoform without the exon 3 of GHR in this group of acromegalic patients is similar to that observed in healthy subjects and to that reported in the literature. On the other hand, the presence of the polymorphism of the GHR is not related to BMI, tumor size, response to treatment, metabolic alterations or to hormonal levels in this group of acromegalic patients evaluated.

Short- and long-term responsiveness to low dose growth hormone (GH) in adult GH deficiency: Role of GH receptor polymorphism.

In patients with growth hormone (GH) deficiency (GHD), low doses of recombinant human GH (rhGH) have a similar or better long-term clinical effect than higher doses. Pharmacogenetic studies suggest that GH receptor (GHR) polymorphism only influences some metabolic parameters. Nonetheless, there is no clear scientific evidence proving the effects of lower rhGH dose regimens on metabolic parameters. The aim of our prospective study was to evaluate the effects of GHR polymorphism in adult GHD patients treated with low rhGH dose during short- (6 and 12months) and long-term (5years) follow-up. Sixty-nine GHD adult patients were studied, before and during treatment with rhGH, using a standardised low-dose protocol calculated on the basis of body weight (0.01-0.03mgkg-1 week-1 ) and monitored by an insulin-like growth factor (IGF)-I plasma assay, as well as anthropometric and metabolic parameters. The GHR genotype (flfl, fld3 or d3d3) was determined from the peripheral blood. d3-GHR carriers showed a more effective short- and long-term response to low rhGH dose with respect to low-density lipoprotein reduction, body composition and blood pressure (homozygous patients only); d3-GHR homozygosity is related to a significant IGF-I increase during short-term follow-up. Regression analysis demonstrated that rhGH dose, age at diagnosis and GHR genotype are the major determinants of IGF-I increase at 6 and 12months of replacement therapy. The d3d3-GHR genotype may influence some metabolic effects during the short- and long-term follow-up of low rhGH dose and could be an independent determinant of the increase of IGF- I during short-term follow-up.

Association between the GHR, GHRHR, and IGF1 gene polymorphisms and milk yield and quality traits in Sarda sheep

The growth hormone receptor (GHR), the growth hormone releasing hormone receptor (GHRHR), and the insulin-like growth factor 1 (IGF1) genes are known to modulate growth, reproduction, and lactation traits in livestock. The aim of the current work was to investigate if the variation of the sheep GHR, GHRHR, and IGF1 genes is associated with milk yield and quality traits. Three hundred eighty dairy Sarda sheep were genotyped for 36 single nucleotide polymorphisms (SNP) mapping to these 3 loci, and records for milk yield and daily fat and protein yield, as well as for fat, protein, casein, lactose, and milk urea contents, pH, somatic cell score, logarithmic bacterial count, and milk energy were obtained. The linkage disequilibrium analysis was performed only for GHR, as both GHRHR and IGF1 had only 1 polymorphic SNP. Haplotype analysis revealed the existence of 7 haplotype blocks in GHR. Two haplotype blocks, including part of the intron 1 and the upstream region, were clearly separated from the remaining 5 blocks by SNP rs412986330, which may be a recombination hotspot. The latter 5 blocks were contiguous, spanning from intron 2 to exon 10. Statistical analysis revealed that the GHR polymorphism is significantly associated with milk traits for daily fat and protein yield and fat, milk urea, and lactose content. Moreover, variation in IGF1 was associated with milk protein and casein content. Data generated in this research provide new insights into the allelic effects of the ovine GHRHR, GHR, and IGF1 genes on milk production and quality traits, information that may be useful in gene-assisted selection programs.

Frequency of the exon 3-deleted/full-length growth hormone receptor polymorphism in Saudi Arabian population.

Objectives:To investigate the frequency of the growth hormone receptor (GHR)-d3 polymorphism in a random sample of Saudi Arabian population from Jazan province, and test the effects of the polymorphism on some anthropometric factors.Methods:This cross-sectional population-based study was conducted during the period from January to April 2017 at the College of Applied Medical Sciences, Jazan University, Southwestern Saudi Arabia. A total of 230 healthy adult male and female volunteers were randomly recruited. Genomic DNA was extracted from the whole blood, and the GHR exon 3 locus was genotyped using multiplex polymerase chain reaction.Results:The distributions of the GHR genotypes were as follows: fl/fl (39.1%), fl/d3 (44.8%), and d3/d3 (16.1%). No statistically significant differences were found between fl/fl, fl/d3, or d3/d3 GHR genotypes in terms of weight (p=0.90), height (p=0.12), or body mass index (BMI) (p=0.83) values.Conclusion:No correlations were found between the GHR-d3 polymorphism and weight, height, or BMI.

MECHANISMS IN ENDOCRINOLOGY: Clinical and pharmacogenetic aspects of the growth hormone receptor polymorphism.

Pharmacogenetics aims to maximize the beneficial effects of a medical therapy by identifying genetic finger prints from responders and non-responders and, thereby improving safety and efficacy profile of the drug. Most subjects who are deficient in growth hormone (GHD) are candidates for recombinant human GH (rhGH) therapy. To date, it is well established that even after adjustments for several clinical variables, such as age, gender, body composition and the age at onset of the GHD, response to rhGH treatment is highly variable among individuals, part of which is believed to be due to genetic factors within the GH system. As the first genetic variant to potentially influence the individual response to rhGH therapy in children with growth disorders, polymorphism in the GH receptor (GHR) has attracted a great interest as a target for pharmacogenetics. Studies have been conducted to compare the functional and molecular effects of the full-length GHR (fl-GHR) isoform with the exon 3 deleted (d3-GHR) isoform in children and adults treated with rhGH therapy. Additionally, the impact of the GHR polymorphism has been investigated in relation to the clinical status and response to medical treatment in acromegaly, especially to the GHR antagonist drug pegvisomant. We have performed a narrative review of the studies performed to date on the association of GHR polymorphism with rhGH response in children and adults, and its potential influence in the medical management of acromegaly. In addition, data from studies on the general population and in other chronic diseases examining a role of this genetic variant in the regulation of growth and metabolism are summarized.

Polymorphism of growth hormone receptor (GHR) gene in Pasundan cattle

Putra WPB, Agung PP, Anwar S, Said S, Hermansyah A. 2017. Polymorphism of growth hormone receptor (GHR) gene in Pasundan cattle. Pros Sem Nas Masy Biodiv Indon 3: 299-303. Identification of genetic polymorphism which controlling to the growth traits could be used as molecular selection for livestock. The objective of this study was to identify the genetic polymorphism of GHR in Pasundan cattle. Total of 119 DNA samples of Pasundan cattle that kept at BSD-BC of Ciamis, West Java was used in this study. The method used in the present study was PCR-RFLP with AluI (AG*CT) restriction enzyme. The result of this study showed that the GHR gene (298 bp) of Pasundan cattle were polymorphic with three genotype type of AA (0.412); AG (0.429) and GG (0.160). The Allelic frequencies of A and G were 0.626 and 0.374 respectively. The estimation of allelic effective numbers (Ne) was 1.873 and no fixation effect indicated (Fis<1.00). The Chi-square (χ2) test showed that the genotypic frequencies of GHR gene in the population tested was in the Hardy-Weinberg equilibrium (HWE). The observed of heterozygosity (Ho) values in this study were higher than expected of heterozygosity (He) value. The polymorphism information content (PIC) value was 0.358 (moderate). The conclusion of this study conducted that the GHR gene of Pasundan cattle was polymorphic and might be used as molecular selection through intensive study. Additional sample from another Pasundan’s population places are needed to provide accurate information about the polymorphism of GHR gene in Pasundan cattle.

Polymorphism of growth hormone receptor (GHR) gene in Nilagiri sheep.

The allelic variation in the regulatory sequence of growth hormone receptor (GHR) gene influences the growth traits of sheep. A study was carried out to find out the polymorphisms associated with exon 10 of GHR gene and its association with growth traits of Nilagiri sheep. The blood samples were collected from Nilagiri sheep (n = 103) reared at Sheep Breeding Research Station, Sandynallah, Tamil Nadu, India. DNA was isolated using the phenol-chloroform extraction procedure and eight samples having amplified product of part of exon 10 (895bp) sequenced. The results indicated transitions of nucleotide G>A at loci G177624A and G177878A. The genotyping frequencies estimated using the tetra-primer amplification refractory mutation system-PCR for GG, GA and AA were 0.262, 0.544 and 0.194, and 0.349, 0.505 and 0.146, respectively. The estimated allele frequencies of G and A nucleotides were 0.5340 and 0.4660, and 0.6015 and 0.3985, respectively, at loci G177624A and G177878A. The effects of both the mutations on growth-related traits viz., birth, weaning (3months) 6, 9 and 12months weight in Nilagiri sheep were found to be non-significant. This can be a novel approach to assess growth of sheep using the mutation in GHR gene. Thus, this approach can be useful for further investigation as a molecular marker associated with genetic improvement.

Growth hormone receptor polymorphisms and growth hormone response to stimulation test: a pilot study.

No gold standard pharmacological stimulation test exists for the diagnosis of growth hormone deficiency (GHD). In addition, the genetic factors that influence growth hormone (GH) responses remain unclear. This study aimed to determine whether polymorphisms in exon 6 of the GH receptor gene influence responses to the L-arginine GH stimulation test. This study included 27 prepubertal patients with confirmed GHD. GHD was defined as a peak GH level <8 ng/mL in response to pharmacological stimulation. The mean GH peak after L-arginine stimulation was 2.9±2.9 ng/mL. The included patients had the following genotypes at the third position of codon 168: AA (N.=1), AG (N.=15) and GG (N.=11). Patients carrying the AA and AG genotypes exhibited stronger responses to arginine than patients with the GG genotype (3.1±2.7 vs. 1.5±1.3 ng/mL, P=0.01). The approach employed in this study could elucidate GH profiles under physiological and pathological conditions, facilitating improved interpretation of pharmacological stimulation tests.

Growth Parameters Evaluation and Identification of Growth Hormone Receptor Gene Polymorphisms in Various Strains of Rainbow Trout Oncorhynchus mykiss

In the present study, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and restriction fragment length polymorphism (RFLP) methods were compared to analyze the polymorphism of growth hormone receptor (GHR) gene in French, Iranian and Danish strains of Oncorhynchus mykiss. A monomorphic SSCP pattern of AA genotype in the French and Iranian strains and a dimorphic AA and AB genotype in the Danish strain were observed in 3' non-coding regions of GHR gene. In the Danish strain, the AB genotype polymorphism of the GHR gene with its very low frequency (5%) has no effect on the production trait. While, RFLP-Dde1 showed no polymorphism with genetic variation in the location of GHR. Moreover, comparing the condition factors (K) of three different rainbow trout strains showed a significant correlation between the French (1.312 ± 0.13), Iranian (1.245 ± 0.17) and Danish strains (0.763 ± 0.1), respectively (p<0.05). In particular, the French strain obtained a higher K compared to the two others. The length-weight relationship is shown by the following equations W= 0.013 × L2.921, W= 0.012 ×L3.023 and W= 0.007 × L3.176 for French, Iranian and Danish strains, respectively. With the mean (b= 2.921), the studied French strain exhibited a negative allometric growth b<3 while the Iranian (b=3.023) and the Danish (b=3.176) showed positive allometric growths. Regardless of the underlying mechanism(s) responsible for the different relationships, the results of this study suggested that the AA and AB genotypes polymorphism of the GHR gene are not associated with condition factor and environmental variables can influence condition factor and length-weight relationship of rainbow trout strains in this study.

Monomorphism Of Growth Hormone Receptor Gene in South Indian Breeds of Sheep

The study of candidate genes, based on physiological effects is an important tool to identify polymorphism of the gene to be used in marker assisted selection programme. On this basis to evaluate genetic diversity, a study was undertaken to identify the polymorphism of growth hormone receptor (GHR) gene as a genetic marker for growth traits in Madras Red, Mecheri and Nilagiri breeds of sheep. Part of exon 10 (895 bp) of GHR gene was amplified with suitable primers. Restriction fragment length polymorphism (RFLP) of the amplified product using Msp and Haelll enzymes was found to be monomorphic in all the three breeds of sheep indicating that the GHRgene is highly conserved and of use in evolutionary studies.