The growth hormone receptor exon 3 deleted/full-length polymorphism is associated with total- and LDL-cholesterol

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 109-133-GHRH, GH & IGF Biology & Signaling
Bench to Bedside
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-124
Camilla AM Glad*1, Lena MS Carlsson1, Lars Sjöström1, Staffan Nilsson2, Johanna Andersson-Assarsson1, Peter Jacobson1, Per-Arne Svensson1 and Gudmundur Johannsson1
1The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden, 2Chalmers University of Technology, Gothenburg, Sweden
Introduction: Obesity is associated with considerable changes in the activity of the growth hormone-insulin-like growth factor I (GH-IGF-I) axis. GH receptors are abundantly expressed in adipose tissue, which is strongly influenced by GH action. The GHR exon 3 deleted/full-length (d3/fl) polymorphism has previously been suggested to influence GH sensitivity in mostly GH deficient (GHD) populations, but its effect on body composition and metabolism in non-GHD populations is unknown.

Aim: To test the hypothesis that a sensitive GHR genotype, the GHR d3/fl polymorphism, is associated with a more favorable body composition and metabolic profile. 

Subjects and Methods: The SOS SibPair study consists of 154 nuclear families (732 subjects in total) with body mass index (BMI) discordant sib-pairs (BMI difference > 10 kg/m2). Average family size was 4.75 individuals. Median BMI (1st-3rd quartiles) was 27.2 (23.0–33.2), range 16.9-57.8. Median age (1st-3rd quartiles) was 45 years (36–63). Genotyping of the GHR d3/fl polymorphism was performed using TaqMan SNP genotyping of tagSNP rs6873545.

Results: The frequency of the d3-GHR was 26.6% (fl/fl 53.9%, fl/d3 38.9% and d3/d3 7.2%). In a linear model adjusting for sex, age and family effects, homozygosity of the d3-GHR was associated with lower systolic blood pressure (SBP; p=0.03), diastolic blood pressure (DBP; p=0.02), total- (p<0.001) and LDL-cholesterol (p<0.001), compared to grouped d3/fl and fl/fl genotypes. After corrections for multiple testing, the association between the GHR d3/fl polymorphism and total- and LDL-cholesterol remained.

Conclusion: This study is the first to show an influence of the GHR d3/fl polymorphism on total- and LDL-cholesterol in a non-GHD population, levels of which are influenced by GH status. The findings in this study provide further support of the involvement of the GH-IGF-I axis in regulation of cardio-metabolic health.

Nothing to Disclose: CAG, LMC, LS, SN, JA, PJ, PAS, GJ

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: This study was supported by grants from the Swedish Research Council (K2010-55X-11285-13, K2008-65X-20753-01-4), the Swedish Foundation for Strategic Research to Sahlgrenska Center for Cardiovascular and Metabolic Research, the Swedish federal government under the LUA/ALF agreement and the University of Gothenburg.