Genotypes associated with lipid metabolism contribute to differences in serum lipid profile of GH-deficient adults before and after GH replacement therapy.
Journal article, 2012
bjective: GH deficiency (GHD) in adults is associated with an altered serum lipid profile that responds to GH replacement therapy (GHRT). This study evaluated the influence of polymorphisms in genes related to lipid metabolism on serum lipid profile before and after 1 year of GHRT in adults. Design and methods: In 318 GHD patients, total cholesterol (TC) serum concentrations, LDL-C, HDL-C, and triglycerides (TG) were assessed. Using a candidate gene approach, 20 single nucleotide polymorphisms (SNPs) were genotyped. GH dose was individually titrated to obtain normal serum IGF1 concentrations. Results: At baseline, the minor alleles of cholesteryl ester transfer protein (CETP) gene SNPs rs708272 and rs1800775 were associated with higher serum TC and apolipoprotein E (APOE) gene SNP rs7412 with lower TC concentrations; CETP SNPs rs708272, rs1800775, and rs3764261 and apolipoprotein B (APOB) gene SNP rs693 with higher serum HDL-C; APOE SNP rs7412, peroxisome proliferator-activated receptor gamma (PPARG) gene SNP rs10865710 with lower LDL-C, and CETP SNP rs1800775 with higher LDL-C; and APOE/C1/C4/C2 cluster SNP rs35136575 with lower serum TG. After treatment, APOB SNP rs676210 GG genotype was associated with larger reductions in TC and LDL-C and PPARG SNP rs10865710 CC genotype with greater TC reduction. All associations remained significant when adjusted for age, sex, and BMI. Conclusions: In GHD adults, multiple SNPs in genes related to lipid metabolism contributed to individual differences in baseline serum lipid profile. The GH treatment response in TC and LDL-C was influenced by polymorphisms in the APOB and PPARG genes.
Dwarfism
Aged
Time Factors
blood
deficiency
Adolescent
Humans
therapeutic use
Lipid Metabolism
Human Growth Hormone
Cohort Studies
drug therapy
Genetic Variation
blood
Young Adult
Longitudinal Studies
Female
genetics
Lipids
Genotype
Pituitary
Adult
physiology
Prospective Studies
Middle Aged
genetics
Male
Author
Edna J L Barbosa
University of Gothenburg
Camilla A M Glad
University of Gothenburg
Anna G Nilsson
University of Gothenburg
Helena Filipsson Nyström
University of Gothenburg
Galina Götherström
University of Gothenburg
Per-Arne Svensson
University of Gothenburg
Isabela Vinotti
Universidade Federal do Parana
Bengt-Åke Bengtsson
University of Gothenburg
Staffan Nilsson
Chalmers, Mathematical Sciences, Mathematical Statistics
University of Gothenburg
Cesar Luiz Boguszewski
Universidade Federal do Parana
Gudmundur Johannsson
University of Gothenburg
European Journal of Endocrinology
08044643 (ISSN) 1479683X (eISSN)
Vol. 167 3 353-62Subject Categories
Clinical Medicine
DOI
10.1530/EJE-12-0263
PubMed
22715478