GH receptor d3 polymorphism in Dutch patients with MPHD and IGHD born small or appropriate for gestational age

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GH acts through the GH receptor (GHR). The GHR gene contains a genetic polymorphism caused by a deletion of exon 3 (d3), with high frequency in the normal population. There is a continuing controversy whether the presence or absence of the exon 3 deletion (d3+ vs. d3–) affects the effect of GH in human growth.

Design, patients and measurements

For 144 patients with idiopathic isolated GH deficiency (IGHD, n = 72) or multiple pituitary hormone deficiency (MPHD, n = 72), amplification of the region around exon 3 of the GHR gene was performed. Clinical data and response to GH treatment were compared between GHR d3+ and d3– IGHD and MPHD patients born either small for gestational age (SGA) or appropriate for gestational age (AGA).


IGHD patients born SGA had a significantly higher d3+ frequency (82%) than IGHD patients born AGA (35%, P = 0·006). Within the group of IGHD patients born SGA, d3– patients showed a slightly better spontaneous catch up growth before start of GH treatment than d3+ patients (1·1 ± 1·1 SD vs. 0·6 ± 1·1 SDS, P = 0·040) There was no difference in patients first year's response to GH treatment between GHR d3+ and d3– patients.


In IGHD and MPHD patients, response to GH treatment was independent of GHR genotype. GHR-d3 was significantly more frequent among IGHD patients born SGA. As we are the third to report an association between birth size and GHR d3 status, it is conceivable that the GHR-d3 might affect prenatal growth in IGHD patients by a yet unknown mechanism.

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