Interaction between PPARG Pro12Ala and ADIPOQ G276T concerning cholesterol levels in childhood obesity.
OBJECTIVE
The aim of this study was to investigate the role of two candidate gene polymorphisms for insulin resistance and lipid levels in obese children and adolescents.


METHODS
Two markers of insulin resistance and lipid levels, Pro12Ala in peroxisome proliferator-activated receptor-gamma2 (PPARG) and G276T in adiponectin (ADIPOQ), were genotyped in 285 obese children and adolescents. As the apolipoprotein E (APOE) polymorphisms C112R and R158C are known to have a profound impact on lipid levels in both children and adults, results were adjusted for APOE genotype.


RESULTS
We found no association for PPARG or ADIPOQ polymorphisms with Body Mass Index (BMI), High Density Lipoprotein (HDL)-cholesterol, triglycerides or Insulin Resistance estimated by Homeostasis Model of Assessment (HOMA-IR). Wild type carriers of PPARG Pro12Ala (p<0.05), homozygous carriers of the variant allele of ADIPOQ G276T (p<0.001) and epsilon4 carriers of APOE (p<0.001) had higher total and low density lipoprotein (LDL)-cholesterol levels adjusted for age, gender, BMI and insulin sensitivity. A PPARG/ADIPOQ risk genotype combination was identified by analysis of covariance (ANCOVA) comparing all existing combinations. Carriers of PPARG Pro/Pro and ADIPOQ 276 T/T had higher total (5.0 [4.1-5.8] vs. 4.1 [3.6-4.6] mmol/l) and LDL-cholesterol levels (3.7 [2.9-4.5] vs. 3.0 [2.5-3.5] mmol/l) compared with carriers of other combinations (p<0.001). Importantly, the PPARG and ADIPOQ associations were unaffected when adjusting for APOE genotype.


CONCLUSIONS
Genetic variants in candidate genes for insulin resistance are associated with cholesterol levels in obese children and adolescents, and may offer additional information in the risk assessment of obese children.
Johansson
Lovisa E
LE
Department of Clinical Sciences Malmö, Clinical Obesity, Lund University, CRC, UMAS, Ing 72, Hus 91, Plan 12, Malmö S-205 02, Sweden. lovisa.johansson@med.lu.se
Danielsson
Pernilla
P
Norgren
Svante
S
Marcus
Claude
C
Ridderstråle
Martin
M
D052242:Adiponectin / Q000235:genetics*; D000293:Adolescent; D000409:Alanine / Q000235:genetics; D015992:Body Mass Index; D002648:Child; D002784:Cholesterol / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008297:Male; D009765:Obesity / Q000097:blood / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors
D052242:Adiponectin; D008055:Lipids; D047495:PPAR gamma; D002784:Cholesterol; D011392:Proline; D000409:Alanine