The GH receptor exon 3 deleted/full-length polymorphism is associated with central adiposity in the general population.
OBJECTIVE
To test the hypothesis that the GH receptor (GHR) exon 3 deleted (d3)/full-length (fl) polymorphism influences anthropometry and body composition in the general population.


METHODS
The Swedish Obese Subjects (SOS) reference study is a cross-sectional population-based study, randomly selected from a population registry. A subgroup of the population-based Malmö Diet and Cancer study (MDC-CC) was used as a replication cohort.


METHODS
The SOS reference study comprises 1135 subjects (46.2% men), with an average age of 49.5 years. The MDC-CC includes 5451 successfully genotyped subjects (41.5% men), with an average age of 57.5 years. GHR d3/fl genotypes were determined using TagSNP rs6873545. Linear regression analyses were used to test for genotype-phenotype associations.


RESULTS
In the SOS reference study, subjects homozygous for the d3-GHR weighed ∼4 kg more (P=0.011), and had larger waist-to-hip ratio (WHR, P=0.036), larger waist circumference (P=0.016), and more fat-free mass estimated from total body potassium (P=0.026) than grouped fl/d3 and fl/fl subjects (d3-recessive genetic model). The association with WHR was replicated in the MDC-CC (P=0.002), but not those with other anthropometric traits.


CONCLUSIONS
In this population-based study, the GHR d3/fl polymorphism was found to be of functional relevance and associated with central adiposity, such that subjects homozygous for the d3-GHR showed an increased abdominal obesity.
Departments of EndocrinologyMolecular and Clinical MedicineInstitute of Medicine, The Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, Vita Stråket 15, SE-413 45 Gothenburg, SwedenDepartment of Clinical SciencesLund University, Malmö, SwedenDepartment of Mathematical StatisticsChalmers University of Technology, Gothenburg, SwedenDepartment of EndocrinologyDiabetology and Metabolism, Sahlgrenska University Hospital, Gothenburg, Sweden camilla.glad@medic.gu.se.
Camilla A M
CA
Glad
Departments of EndocrinologyMolecular and Clinical MedicineInstitute of Medicine, The Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, Vita Stråket 15, SE-413 45 Gothenburg, SwedenDepartment of Clinical SciencesLund University, Malmö, SwedenDepartment of Mathematical StatisticsChalmers University of Technology, Gothenburg, SwedenDepartment of EndocrinologyDiabetology and Metabolism, Sahlgrenska University Hospital, Gothenburg, Sweden.
Lena M S
LM
Carlsson
Departments of EndocrinologyMolecular and Clinical MedicineInstitute of Medicine, The Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, Vita Stråket 15, SE-413 45 Gothenburg, SwedenDepartment of Clinical SciencesLund University, Malmö, SwedenDepartment of Mathematical StatisticsChalmers University of Technology, Gothenburg, SwedenDepartment of EndocrinologyDiabetology and Metabolism, Sahlgrenska University Hospital, Gothenburg, Sweden.
Olle
O
Melander
Departments of EndocrinologyMolecular and Clinical MedicineInstitute of Medicine, The Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, Vita Stråket 15, SE-413 45 Gothenburg, SwedenDepartment of Clinical SciencesLund University, Malmö, SwedenDepartment of Mathematical StatisticsChalmers University of Technology, Gothenburg, SwedenDepartment of EndocrinologyDiabetology and Metabolism, Sahlgrenska University Hospital, Gothenburg, Sweden.
Peter
P
Almgren
Departments of EndocrinologyMolecular and Clinical MedicineInstitute of Medicine, The Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, Vita Stråket 15, SE-413 45 Gothenburg, SwedenDepartment of Clinical SciencesLund University, Malmö, SwedenDepartment of Mathematical StatisticsChalmers University of Technology, Gothenburg, SwedenDepartment of EndocrinologyDiabetology and Metabolism, Sahlgrenska University Hospital, Gothenburg, Sweden.
Lars
L
Sjöström
Departments of EndocrinologyMolecular and Clinical MedicineInstitute of Medicine, The Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, Vita Stråket 15, SE-413 45 Gothenburg, SwedenDepartment of Clinical SciencesLund University, Malmö, SwedenDepartment of Mathematical StatisticsChalmers University of Technology, Gothenburg, SwedenDepartment of EndocrinologyDiabetology and Metabolism, Sahlgrenska University Hospital, Gothenburg, Sweden.
Staffan
S
Nilsson
Departments of EndocrinologyMolecular and Clinical MedicineInstitute of Medicine, The Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, Vita Stråket 15, SE-413 45 Gothenburg, SwedenDepartment of Clinical SciencesLund University, Malmö, SwedenDepartment of Mathematical StatisticsChalmers University of Technology, Gothenburg, SwedenDepartment of EndocrinologyDiabetology and Metabolism, Sahlgrenska University Hospital, Gothenburg, Sweden.
Ingrid
I
Larsson
Departments of EndocrinologyMolecular and Clinical MedicineInstitute of Medicine, The Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, Vita Stråket 15, SE-413 45 Gothenburg, SwedenDepartment of Clinical SciencesLund University, Malmö, SwedenDepartment of Mathematical StatisticsChalmers University of Technology, Gothenburg, SwedenDepartment of EndocrinologyDiabetology and Metabolism, Sahlgrenska University Hospital, Gothenburg, Sweden.
Per-Arne
PA
Svensson
Departments of EndocrinologyMolecular and Clinical MedicineInstitute of Medicine, The Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, Vita Stråket 15, SE-413 45 Gothenburg, SwedenDepartment of Clinical SciencesLund University, Malmö, SwedenDepartment of Mathematical StatisticsChalmers University of Technology, Gothenburg, SwedenDepartment of EndocrinologyDiabetology and Metabolism, Sahlgrenska University Hospital, Gothenburg, Sweden.
Gudmundur
G
Johannsson
D000368:Aged; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005091:Exons / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D056726:Genetic Association Studies / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011159:Population Surveillance / Q000379:methods; D011446:Prospective Studies; D011986:Receptors, Somatotropin / Q000235:genetics*; D013548:Sweden / Q000453:epidemiology
D011986:Receptors, Somatotropin