Growth hormone receptor polymorphism and growth hormone therapy response in children: a Bayesian meta-analysis.

Recombinant human growth hormone (rhGH) therapy is used in the long-term treatment of children with growth disorders, but there is considerable treatment response variability. The exon 3-deleted growth hormone receptor polymorphism (GHR(d3)) may account for some of this variability. The authors performed a systematic review (to April 2011), including investigator-only data, to quantify the effects of the GHR(fl-d3) and GHR(d3-d3) genotypes on rhGH therapy response and used a recently established Bayesian inheritance model-free approach to meta-analyze the data.

D3 GH receptor polymorphism is not associated with IGF1 levels in untreated acromegaly.

Context: A discrepancy between serum GH and IGF1 concentrations is frequent in patients with acromegaly. Here, we examined whether the exon 3-deleted (d3) GH receptor (GHR) variant, which has been linked to increased responsiveness to GH treatment in short children, influences the GH/IGF1 relationship in patients with acromegaly.

Objective: To study the possible influence of the GHR genotype on the GH/IGF1 relationship in untreated acromegalic patients.

A single-nucleotide polymorphism in a methylatable Foxa2 binding site of the G6PC2 promoter is associated with insulin secretion in vivo and increased promoter activity in vitro.

Objective: The G6PC2 gene encoding islet-specific glucose-6-phosphatase related protein (IGRP) has a common promoter variant, rs573225 (-231G/A), located within a Foxa binding site. We tested the cis-regulatory effects of rs573225 on promoter activity and its association with insulin response to oral glucose.

Research Design And Methods: Functional effects of rs573225 were explored in transfected INS-1 and HIT-T beta-cell lines.

A common polymorphism of the growth hormone receptor is associated with increased responsiveness to growth hormone.

Growth hormone is used to increase height in short children who are not deficient in growth hormone, but its efficacy varies largely across individuals. The genetic factors responsible for this variation are entirely unknown. In two cohorts of short children treated with growth hormone, we found that an isoform of the growth hormone receptor gene that lacks exon 3 (d3-GHR) was associated with 1.

The common -866 G/A polymorphism in the promoter of uncoupling protein 2 is associated with increased carbohydrate and decreased lipid oxidation in juvenile obesity.

Uncoupling protein (UCP) 2 is a member of the mitochondrial transporter superfamily that uncouples proton entry in the mitochondrial matrix from ATP synthesis. Although its physiological role remains to be established, UCP2 is considered a candidate gene for association with energy metabolism and obesity. A common promoter polymorphism, -866 G/A, has been associated with increased UCP2 gene expression and middle-aged adult obesity.

INS VNTR is a QTL for the insulin response to oral glucose in obese children.

We performed a genotype-phenotype association study to examine whether the insulin VNTR (INS VNTR) polymorphism located in the insulin gene promoter was associated with changes in insulin response to oral glucose. Two classes of INS VNTR alleles are observed in Caucasians, the "short" class I and the "long" class III. Plasma insulin and glucose concentrations and indices of insulin secretion (IGI) and sensitivity (ISI) were measured using an oral glucose tolerance test (OGTT) in 387 obese children aged 12 +/- 0.