Session: SAT 109-133-GHRH, GH & IGF Biology & Signaling
Bench to Bedside
Poster Board SAT-124
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
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