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Lack of association between FTO gene variations and metabolic healthy obese (MHO) phenotype: Tehran Cardio-metabolic Genetic Study (TCGS)

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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

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Acknowledgements

The study was done under supervision of Cellular and Molecular Endocrine Research Center and Obesity research center in the Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Funding

This study supported by the Iran National Scientific Foundation, Tehran, Iran (Grant number 93017278).

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Authors and Affiliations

  1. Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, PO Box 19195-4763, Tehran, Islamic Republic of Iran

    Bahareh Sedaghati-khayat, Mahdi Akbarzadeh, Kamran Guity & Maryam S. Daneshpour

  2. Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran

    Maryam Barzin

  3. Kawsar Human Genetics Research Center, Tehran, Islamic Republic of Iran

    Mohammad-Sadegh Fallah

  4. Department of Internal Medicine, University of California Riverside, Riverside, CA, USA

    Hoda Pourhassan

  5. Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran

    Fereidoun Azizi

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  1. Bahareh Sedaghati-khayat
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The study protocol was approved by the ethics committee of the Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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Sedaghati-khayat, B., Barzin, M., Akbarzadeh, M. et al. Lack of association between FTO gene variations and metabolic healthy obese (MHO) phenotype: Tehran Cardio-metabolic Genetic Study (TCGS). Eat Weight Disord 25, 25–35 (2020). https://doi.org/10.1007/s40519-018-0493-2

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