Genotypes associated with lipid metabolism contribute to differences in serum lipid profile of GH-deficient adults before and after GH replacement therapy.
OBJECTIVE
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.


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.
Department of Endocrinology, Institute of Medicine, Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, Gröna Straket 8, SE-413 45 Gothenburg, Sweden. edna.barbosa@medic.gu.se
Edna J L
EJ
Barbosa
Camilla A M
CA
Glad
Anna G
AG
Nilsson
Helena
H
Filipsson Nyström
Galina
G
Götherström
Per-Arne
PA
Svensson
Isabela
I
Vinotti
Bengt-Åke
BÅ
Bengtsson
Staffan
S
Nilsson
Cesar Luiz
CL
Boguszewski
Gudmundur
G
Johannsson
D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004393:Dwarfism, Pituitary / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D019382:Human Growth Hormone / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D008055:Lipids / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D055815:Young Adult
D008055:Lipids; D019382:Human Growth Hormone