title: FTO Is Associated with Aortic Valve Stenosis in a Gender Specific Manner of Heterozygote Advantage: A Population-Based Case-Control Study.
abstract: BACKGROUND
  Single nucleotide polymorphisms (SNPs) within the Fat mass and obesity associated (FTO) gene have been linked with increased body weight. However, the data on an association of FTO with cardiovascular diseases remains conflicting. Therefore, we ascertained whether FTO is associated with aortic valve stenosis (AVS), one of the most frequent cardiovascular diseases in the Western world.
  
  
  RESULTS
  In this population-based case-control study the FTO SNP rs9939609 was analyzed in 300 German patients with AVS and 429 German controls of the KORA survey S4, representing a random population. Blood samples were collected prior to aortic valve replacement in AVS cases and FTO rs9939609 was genotyped via ARMS-PCR. Genotype frequencies differed significantly between AVS cases and KORA controls (p = 0.004). Separate gender-analyses uncovered an association of FTO with AVS exclusively in males; homozygote carriers for the risk-allele (A) had a higher risk to develop AVS (p = 0.017, odds ratio (OR) 1.727; 95% confidence interval (CI) 1.087-2.747, recessive model), whereas heterozygote carriers for the risk-allele showed a lower risk (p = 0.002, OR 0.565, 95% CI 0.384-0.828, overdominant model). After adjustment for multiple co-variables, the odds ratios of heterozygotes remained significant for an association with AVS (p = 0.008, OR 0.565, 95% CI 0.369-0.861).
  
  
  CONCLUSIONS
  This study revealed an association of FTO rs9939609 with AVS. Furthermore, this association was restricted to men, with heterozygotes having a significantly lower chance to develop AVS. Lastly, the association between FTO and AVS was independent of BMI and other variables such as diabetes mellitus.
authors.affiliation: Institute for Animal Developmental and Molecular Biology, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Cindy
authors.initials: C
authors.lastname: Thron
authors.affiliation: Department of Cardiovascular Surgery, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Payam
authors.initials: P
authors.lastname: Akhyari
authors.affiliation: Department of Cardiovascular Surgery, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Erhard
authors.initials: E
authors.lastname: Godehardt
authors.affiliation: Department of Cardiovascular Surgery, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Artur
authors.initials: A
authors.lastname: Lichtenberg
authors.affiliation: Institute for Animal Developmental and Molecular Biology, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Rüther
authors.affiliation: Institute for Animal Developmental and Molecular Biology, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Seehaus
mesh_terms: D000368:Aged; D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001024:Aortic Valve Stenosis / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005858:Germany / Q000453:epidemiology; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics*; D012306:Risk; D012727:Sex Characteristics; D014463:Ultrasonography
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human