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The GH receptor exon 3 deleted/full-length polymorphism is associated with central adiposity in the general
Camilla A M Glad1, Lena M S Carlsson2, Olle Melander2
1Departments 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.
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.
Design And Setting:
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.
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