Impact of FTO genotypes on BMI and weight in polycystic ovary syndrome: a systematic review and meta-analysis.
OBJECTIVE
FTO gene single nucleotide polymorphisms (SNPs) have been shown to be associated with obesity-related traits and type 2 diabetes. Several small studies have suggested a greater than expected effect of the FTO rs9939609 SNP on weight in polycystic ovary syndrome (PCOS). We therefore aimed to examine the impact of FTO genotype on BMI and weight in PCOS.


METHODS
A systematic search of medical databases (PubMed, EMBASE and Cochrane CENTRAL) was conducted up to the end of April 2011. Seven studies describing eight distinct PCOS cohorts were retrieved; seven were genotyped for SNP rs9939609 and one for SNP rs1421085. The per allele effect on BMI and body weight increase was calculated and subjected to meta-analysis.


RESULTS
A total of 2,548 women with PCOS were included in the study; 762 were TT homozygotes, 1,253 had an AT/CT genotype, and 533 were AA/CC homozygotes. Each additional copy of the effect allele (A/C) increased the BMI by a mean of 0.19 z score units (95% CI 0.13, 0.24; p = 2.26 × 10(-11)) and body weight by a mean of 0.20 z score units (95% CI 0.14, 0.26; p = 1.02 × 10(-10)). This translated into an approximately 3.3 kg/m(2) increase in BMI and an approximately 9.6 kg gain in body weight between TT and AA/CC homozygotes. The association between FTO genotypes and BMI was stronger in the cohorts with PCOS than in the general female populations from large genome-wide association studies. Deviation from an additive genetic model was observed in heavier populations.


CONCLUSIONS
The effect of FTO SNPs on obesity-related traits in PCOS seems to be more than two times greater than the effect found in large population-based studies. This suggests an interaction between FTO and the metabolic context or polygenic background of PCOS.
HTA Consulting, Krakow, Poland.
P
P
Wojciechowski
School of Medicine, Emory University, Atlanta, GA, USA.
A
A
Lipowska
HTA Consulting, Krakow, Poland.
P
P
Rys
Department of Genetics, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
K G
KG
Ewens
Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, London, UK.
S
S
Franks
Department of Endocrinology, University of Duisburg-Essen, Essen, Germany.
S
S
Tan
Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.
E
E
Lerchbaum
Institute of Endocrinology, Prague, Czech Republic.
J
J
Vcelak
Molecular Endocrinology Laboratory, UMR-204 NUTRIPASS, Institut Universitaire de Recherche Clinique (IURC), Montpellier, France.
R
R
Attaoua
Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
M
M
Straczkowski
Department of Obstetrics and Gynecology, Georgia Health Sciences University, Augusta, GA, USA.
R
R
Azziz
Department of Metabolic and Vascular Health, Clinical Sciences Research Laboratories, Warwick Medical School, Coventry, UK.
T M
TM
Barber
Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany.
A
A
Hinney
Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.
B
B
Obermayer-Pietsch
Institute of Endocrinology, Prague, Czech Republic.
P
P
Lukasova
Institute of Endocrinology, Prague, Czech Republic.
B
B
Bendlova
Molecular Endocrinology Laboratory, UMR-204 NUTRIPASS, Institut Universitaire de Recherche Clinique (IURC), Montpellier, France.
F
F
Grigorescu
Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
I
I
Kowalska
Division of Endocrinology, Diabetes, and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
M O
MO
Goodarzi
Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, USA.
J F
JF
Strauss
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.|Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
M I
MI
McCarthy
Department of Metabolic Diseases, Jagiellonian University Medical College, 15 Kopernika Street, 31-501, Krakow, Poland. malecki_malecki@yahoo.com.|University Hospital, Krakow, Poland. malecki_malecki@yahoo.com.
M T
MT
Malecki
D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics* / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D009765:Obesity / Q000235:genetics / Q000503:physiopathology; D017063:Outcome Assessment, Health Care; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011506:Proteins / Q000235:genetics*
D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human