The exon-3 deleted growth hormone receptor polymorphism predisposes to long-term complications of acromegaly.
OBJECTIVE
The aim of the study was to evaluate the impact of the genomic deletion of exon 3 of the GH receptor (d3GHR) on long-term clinical outcome of acromegaly in a well-characterized cohort of patients with long-term remission of acromegaly.


METHODS
We conducted a cross-sectional study.


METHODS
The presence of the d3GHR polymorphism was assessed in 86 acromegalic patients with long-term disease control and related to anthropometric parameters, cardiovascular risk factors, osteoarthritis, bone mineral density, colonic polyps and diverticulae, and dolichocolon.


RESULTS
Fifty-one patients had two wild-type alleles (59%), whereas 29 patients (34%) had one allele and six patients (7%) had two alleles encoding for the d3GHR isoform. Carriers of the d3GHR isoform showed increased prevalence of osteoarthritis, especially of the hip [adjusted odds ratio (OR), 5.2; 95% confidence interval (CI), 3.2-7.1], of adenomatous polyps (adjusted OR, 4.1; 95% CI, 2.4-5.6), and dolichocolon (adjusted OR, 3.2; 95% CI, 1.8-4.6). Anthropometric parameters, cardiovascular risk factors, bone mineral density, and (non)vertebral fractures were not significantly different between patients with and without the d3GHR allele.


CONCLUSIONS
In patients with long-term cured acromegaly, the d3GHR polymorphism is associated with an increased prevalence of irreversible comorbidities such as osteoarthritis, dolichocolon, and adenomatous colonic polyps, but not with other comorbidities such as cardiovascular risk factors.
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
M J E
MJ
Wassenaar
N R
NR
Biermasz
A M
AM
Pereira
A A
AA
van der Klaauw
J W A
JW
Smit
F
F
Roelfsema
T
T
van der Straaten
M
M
Cazemier
D W
DW
Hommes
H M
HM
Kroon
M
M
Kloppenburg
H-J
HJ
Guchelaar
J A
JA
Romijn
D000172:Acromegaly / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000886:Anthropometry; D015519:Bone Density / Q000235:genetics / Q000502:physiology; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics; D015331:Cohort Studies; D003108:Colonic Diseases / Q000453:epidemiology / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005091:Exons / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D019382:Human Growth Hormone / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics; D010024:Osteoporosis / Q000453:epidemiology / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics* / Q000502:physiology*; D011859:Radiography; D011986:Receptors, Somatotropin / Q000235:genetics* / Q000502:physiology*; D012307:Risk Factors; D016103:Spinal Fractures / Q000453:epidemiology / Q000235:genetics; D016896:Treatment Outcome
D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D004247:DNA