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Submitted on August 8, 2006
Accepted on October 30, 2006
Endocrine Research Laboratory, MUHC-Montreal Children's Hospital Research Institute, Division of Experimental Medicine, McGill University, Depts of Laboratory Medicine and Pathobiology and Pediatrics, University of Toronto, and Dept of Pediatrics, McGill University
* To whom correspondence should be addressed. E-mail: cindy.goodyer{at}muhc.mcgill.ca.
Context: Three recent clinical studies have reported that two of the most common isoforms of the human GH receptor (hGHR), exon 3 full length (3+) and exon 3 deleted (3-), may have differential effects on the growth response of children receiving hGH therapy while others refute this. However, none of the investigations have explored the relationship between these hGHR isoforms and final adult height (FAH) or measures of bone mineral density (BMD) within a healthy adult population.
Objective: To investigate the possible influences of hGHR exon 3 isoforms on FAH and BMD measures of a normal population.
Design: To correlate the hGHR exon 3 genotype of a cohort of healthy adults well-characterized with respect to FAH, BMDs (spine [L2-L4] and hip [femoral neck]), and quantitative ultrasound (QUS) of the heel.
Patients: 368 unrelated healthy adult Caucasian women, aged 18-35 yr.
Main outcome measures: Association measures of hGHR exon 3 genotypes with FAH, BMD, and QUS. Heights were measured using a stadiometer, BMDs using dual-energy x-ray absorptiometry, and QUS by standard technique. Detailed medical histories, including lifestyle factors, were obtained using a standardized interview.
Results: The distribution of hGHR genotypes in the 368 samples was 53.3% for 3+/3+, 35.6% for 3+/3-, and 11.1% for 3-/3-. No correlation between the hGHR exon 3 genotypes and FAH, BMD or QUS in this cohort.
Conclusion: The hGHR 3+ and 3- isoforms appear not to have differential effects on two major growth outcomes of hGH action, FAH and BMD, in a population of healthy adult women.
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