Lack of Association between FTO Gene Variations and Metabolic Healthy Obese (MHO) Phenotype: Tehran Cardio-Metabolic Genetic Study (TCGS)

Background: Obesity is currently an international epidemic and metabolic derangements pose these individuals at greater risk for future morbidity and mortality. Genetics and environmental factors have undeniable effects and among genetic risk factors, FTO/CETP genes are important. The current study examines the interaction between obesity phenotypes and FTO/CETP SNPs and their effects on lipid profile changes. Material and methods: We selected 954 adult subjects from TCGS (47.9% male). Participants were stratified according to their BMI and presence of metabolic syndrome according to the Joint Interim Statement (JIS) definition. Nine selected polymorphisms from FTO/CETP genes were genotyped using Tetra ARMS-PCR method. After age and sex adjustment the interaction of 9 markers with lipid profiles among phenotypes were tested by PASW. Results: In three main groups, HDL-C level had a strong significant association with CETP markers: (rs3764261, β(95%CI) -0.48(-0.61-0.35), P=1.0 × 10-11), (rs1800775, β(95%CI) 0.5(0.36;0.65), P=1.0 × 10-6) and (rs1864163, β(95%CI) 0.3(0.16;0.43), P=9.1 × 10-5). This association was also seen in rs7202116 within the total population. In only unhealthy metabolic obese (MUHO) subgroups four new FTO markers (rs1421085, rs1121980, rs1558902 and rs8050136) (P-value<0.01) demonstrated significant association, even after lipid profile adjustment. Conclusion: In the present study, we investigated the association between obesity phenotypes and some variations in FTO/CETP genes for the first time. Our study showed that four markers in the first intron of the FTO gene should be the risk marker in MUHO participants.