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Genetics and Epigenetics

Single-nucleotide polymorphisms in a cohort of significantly obese women without cardiometabolic diseases

International Journal of Obesity volume 43, pages 253–262 (2019)Cite this article

Subjects

Abstract

Background/Objectives

Obesity is an important risk factor for the development of diseases such as diabetes mellitus, hypertension, and dyslipidemia; however, a small number of individuals with long-standing obesity do not present with these cardiometabolic diseases. Such individuals are referred to as metabolically healthy obese (MHO) and potentially represent a subgroup of the general population with a protective genetic predisposition to obesity-related diseases. We hypothesized that individuals who were metabolically healthy, but significantly obese (BMI ≥ 35 kg/m2) would represent a highly homogenous subgroup, with which to investigate potential genetic associations to obesity. We further hypothesized that such a cohort may lend itself well to investigate potential genotypes that are protective with respect to the development of cardiometabolic disease.

Subjects/Methods

In the present study, we implemented this novel selection strategy by screening 892 individuals diagnosed as Class 2 or Class 3 obese and identified 38 who presented no manifestations of cardiometabolic disease. We then assessed these subjects for single-nucleotide polymorphisms (SNPs) that associated with this phenotype.

Results

Our analysis identified 89 SNPs that reach statistical significance (p < 1 × 10−5), some of which are associated with genes of biological pathways that influences dietary behavior; others are associated with genes previously linked to obesity and cardiometabolic disease as well as neuroimmune disease. This study, to the best of our knowledge, represents the first genetic screening of a cardiometabolically healthy, but significantly obese population.

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Acknowledgements

We are grateful to the Coriell Genotyping and Microarray Center at Coriell Institute for Medical Research in Camden, NJ, and to its former Director, Dr. Norman P. Gerry, for their assistance in processing our specimens. This work was funded in part by the National Institute of General Medical Sciences (GM103440).

Author information

Author notes

  1. Karen A. Schlauch

    Present address: Desert Research Institute, Reno, NV, USA

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Nevada, Reno, NV, USA

    Karen A. Schlauch

  2. Nevada INBRE Bioinformatics Core, University of Nevada, Reno, NV, USA

    Karen A. Schlauch

  3. The Mayo Clinic, Scottsdale, AZ, USA

    Doina Kulick

  4. Nevada Center for Biomedical Research, Reno, NV, USA

    Krishnamurthy Subramanian, Kenny L. De Meirleir & Vincent C. Lombardi

  5. Asklepios-Med, Szeged, Hungary

    András Palotás

  6. Kazan Federal University, Kazan, Russian Federation

    András Palotás

  7. Department of Pathology, University of Nevada, Reno, School of Medicine, Reno, NV, USA

    Vincent C. Lombardi

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  1. Karen A. Schlauch
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Correspondence to András Palotás or Vincent C. Lombardi.

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Schlauch, K.A., Kulick, D., Subramanian, K. et al. Single-nucleotide polymorphisms in a cohort of significantly obese women without cardiometabolic diseases. Int J Obes 43, 253–262 (2019). https://doi.org/10.1038/s41366-018-0181-3

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