Genetics
CETP markers show strong associations with HDL cholesterol across obesity phenotypes in an Iranian cohort, unlike most FTO variants (Eat Weight Disord 2020)
Original title: Lack of association between FTO gene variations and metabolic healthy obese (MHO) phenotype: Tehran Cardio-metabolic Genetic Study (TCGS)
This case-control study from the Tehran Cardio-metabolic Genetic Study examined the interaction between obesity phenotypes and FTO/CETP single nucleotide polymorphisms and their effects on lipid profile in 954 adults, stratified by BMI and metabolic syndrome status. Nine polymorphisms from the FTO and CETP genes were genotyped and tested for interaction with lipid profiles after age and sex adjustment. Across the three main groups, HDL-cholesterol showed a strong significant association with three CETP markers: rs3764261 (beta -0.48, 95% CI -0.61 to -0.35, p=1.0x10-11), rs1800775 (beta 0.5, 95% CI 0.36-0.65, p=1.0x10-6), and rs1864163 (beta 0.3, 95% CI 0.16-0.43, p=9.1x10-5), an association also seen for rs7202116 in the total population. Only in the metabolically unhealthy obese subgroup did four FTO markers show significant association, even after lipid profile adjustment.
Original abstract
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.
Materials 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 to - 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.
Level Of Evidence: Level III, case-control study.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.