FTO Is Associated with Aortic Valve Stenosis in a Gender Specific Manner of Heterozygote Advantage: A Population-Based Case-Control Study

• Published in: PloS one 2015-10, Vol.10 (10), p.e0139419-e0139419
• Main Authors: Thron, Cindy, Akhyari, Payam, Godehardt, Erhard, Lichtenberg, Artur, Rüther, Ulrich, Seehaus, Stefanie
• Format: Article
• Language: English
• Subjects: Aged; Alleles; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Angina pectoris; Aorta; Aortic valve; Aortic valve stenosis; Aortic Valve Stenosis - diagnostic imaging; Aortic Valve Stenosis - epidemiology; Aortic Valve Stenosis - genetics; Body fat; Body mass; Body Mass Index; Body weight; Cardiovascular diseases; Carriers; Case-Control Studies; Comorbidity; Complications and side effects; Confidence intervals; Development and progression; Diabetes; Diabetes mellitus; Diabetes Mellitus - epidemiology; Diabetes Mellitus - genetics; Female; Gender; Gene Frequency; Genetic aspects; Genotype & phenotype; Genotypes; Germany - epidemiology; Heart diseases; Heart surgery; Heterozygote; Heterozygote advantage; Heterozygotes; Humans; Hypertension - epidemiology; Hypertension - genetics; Male; Males; Mathematical models; Middle Aged; Molecular biology; Obesity; Overweight - epidemiology; Overweight - genetics; Physiological aspects; Polymorphism, Single Nucleotide; Population studies; Population-based studies; Prospective Studies; Proteins - genetics; Risk; Sex Characteristics; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Stenosis; Studies; Ultrasonography; Yang, Cindy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0139419

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. 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). 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.