'Fat mass and obesity associated' gene (FTO): no significant association of variant rs9939609 with weight loss in a lifestyle intervention and lipid metabolism markers in German obese children and adolescents.
BACKGROUND
We have previously identified strong association of six single nucleotide polymorphisms (SNPs) in FTO (fat mass and obesity associated gene) to early onset extreme obesity within the first genome wide association study (GWA) for this phenotype. The aim of this study was to investigate whether the obesity risk allele of one of these SNPs (rs9939609) is associated with weight loss in a lifestyle intervention program. Additionally, we tested for association of rs9939609 alleles with fasting blood parameters indicative of glucose and lipid metabolism.


METHODS
We initially analysed rs9939609 in a case-control study comprising 519 German overweight and obese children and adolescents and 178 normal weight adults. In 207 of the obese individuals who took part in the outpatient obesity intervention program 'Obeldicks' we further analysed whether carrier status of the obesity risk A-allele of rs9939609 has a differential influence on weight loss after the intervention program. Additionally, we investigated in 480 of the overweight and obese patients whether rs9939609 is associated with fasting blood levels of glucose, triglycerides and HDL and LDL-cholesterol. Genotyping was performed using allele specific polymerase chain reaction (ARMS-PCR). For the association study (case-control approach), the Cochran-Armitage trend test was applied. Blood parameters were analysed using commercially available test kits and the log10-transformed blood parameters and changes in BMI-standard deviation scores (BMI-SDS) were analysed by linear regression with sex and age as covariates under an additive mode of inheritance with the rs9939609 A-allele as risk allele.


RESULTS
We confirmed the association of the risk A-allele of rs9939609 with overweight and early onset obesity (one sided p = 0.036). However, we observed no association of rs9939609 alleles with weight loss or fasting levels of blood glucose, triglycerides and cholesterol.


CONCLUSIONS
We confirmed the rs9939609 A-allele as a risk factor for early onset obesity whereas its impact on weight loss or on serum levels of glucose, triglycerides and cholesterol could not be detected in our samples.


BACKGROUND
This study is registered at clinicaltrials.gov (NCT00435734).
Müller
Timo D
TD
Department of Child and Adolescent Psychiatry and Psychotherapy, University of Duisburg-Essen, Essen, Germany. Timo.Mueller@uni-duisburg-essen.de
Hinney
Anke
A
Scherag
André
A
Nguyen
Thuy T
TT
Schreiner
Felix
F
Schäfer
Helmut
H
Hebebrand
Johannes
J
Roth
Christian L
CL
Reinehr
Thomas
T
D000293:Adolescent; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001786:Blood Glucose / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005500:Follow-Up Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany; D006801:Humans; D008019:Life Style; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D009765:Obesity / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D014280:Triglycerides / Q000097:blood; D015431:Weight Loss / Q000235:genetics
D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005819:Genetic Markers; D011506:Proteins; D014280:Triglycerides; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human
PLoS Genet. 2007 Jul;3(7):e115
17658951
Science. 2007 May 11;316(5826):889-94
17434869
Diabetologia. 2007 Oct;50(10):2218-20
17657473
Science. 2007 Jun 1;316(5829):1341-5
17463248
Diabetes. 2008 May;57(5):1419-26
18346983
Science. 2007 Nov 30;318(5855):1469-72
17991826
Obesity (Silver Spring). 2008 Aug;16(8):1969-72
18535549
Diabetologia. 2007 Dec;50(12):2602-3
17917711
Nat Genet. 2007 Jun;39(6):724-6
17496892
Int J Obes Relat Metab Disord. 2003 Sep;27(9):1087-92
12917715
J Pediatr. 2007 Jun;150(6):618-22, 622.e1-5
17517246
PLoS One. 2007 Dec 26;2(12):e1361
18159244
Am J Clin Nutr. 2006 Sep;84(3):490-6
16960161
Nucleic Acids Res. 2001 Sep 1;29(17):E88-8
11522844
BMC Biochem. 2007 Nov 08;8:23
17996046