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Polymorphisms in Genes Involved in the Leptin-Melanocortin Pathway are Associated with Obesity-Related Cardiometabolic Alterations in a Southern Chilean Population

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Abstract

Background

Polymorphisms in genes encoding proteins of the leptin-melanocortin pathway have been associated with obesity. The involvement of these polymorphisms with changes in body mass index (BMI) and anthropometric measures could also imply a contribution to the risk of metabolic syndrome (MetS) and metabolic alterations. We evaluated the relationship of leptin-melanocortin system polymorphisms with obesity, MetS, and other metabolic alterations in Southern Chilean individuals.

Methods

Two-hundred individuals were grouped as normoweight (BMI 18.0–24.9 kg/m2), overweight (BMI 25.0–29.9 kg/m2), and obese (BMI ≥ 30 kg/m2) or according to MetS status. Anthropometric measures (BMI, abdominal circumference, waist-to-hip ratio [WHR]) and biochemical parameters (glycemia and lipid profile) were evaluated. Polymorphisms LEP rs7799039, LEPR rs1137101, MC3R rs3746619 and rs3827103, and MC4R rs17782313 were evaluated by real-time PCR using allelic discrimination assays.

Results

LEPR rs1137101 GG genotype was related to reduced risk of obesity (odds ratio [OR] 0.26, 95% confidence interval [CI] 0.08–0.79; p = 0.018) and MetS (OR 0.36, 95% CI 0.15–0.88; p = 0.024), but it was not significant after Bonferroni correction for multiple tests as compared to the AA genotype (p > 0.01). Moreover, LEPR rs1137101 allele G (AG + GG) was related to lower BMI and WHR (p < 0.01). Further multiple linear regression analysis demonstrated that this genotype was also responsible for reduced BMI in 2.44 kg/m2 and WHR in 0.033 units. MC4R rs17782313 allele C (TC + CC) was slightly associated with diminished risk of MetS (OR 0.48, 95% CI 0.23–0.98; p = 0.040) and reduced BMI values in 1.95 kg/m2 (p < 0.05). Regarding lipid profile, LEPR rs1137101 allele G carriers had lower triglycerides and very-low-density lipoprotein (VLDL) cholesterol, whereas individuals carrying the MC4R rs17782313 allele C had higher high-density lipoprotein (HDL) cholesterol (p < 0.01). LEP rs7799039 allele A (GA + AA) was slightly associated with reduced total and low-density lipoprotein (LDL) cholesterol (p < 0.05).

Conclusions

These results suggest that polymorphisms at LEP, LEPR, and MC4R may be useful biomarkers of obesity-related cardiometabolic alterations in our population.

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Acknowledgements

We thank the volunteers that participated in this research. Mario H. Hirata and Rosario D.C. Hirata are recipients of fellowships from CNPq-Brazil.

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Authors and Affiliations

  1. Department of Basic Sciences, Center of Excellence in Translational Medicine, BIOREN, Universidad de La Frontera, Av Alemania 0458, Edificio de Biociencias 4º piso, Temuco, Chile

    Victor Manriquez, Jorge Aviles & Alvaro Cerda

  2. Department of Basic Sciences, Center of Molecular Biology and Pharmacogenetics, BIOREN, Universidad de La Frontera, Temuco, Chile

    Luis Salazar, Nicolas Saavedra & Fernando Lanas

  3. Department of Internal Medicine, Universidad de La Frontera, Temuco, Chile

    Pamela Seron & Fernando Lanas

  4. Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil

    Cristina Moreno Fajardo, Mario Hiroyuki Hirata & Rosario Dominguez Crespo Hirata

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  1. Victor Manriquez
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  2. Jorge Aviles
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  3. Luis Salazar
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Correspondence to Alvaro Cerda.

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Conflict of interest

Victor Manriquez, Jorge Aviles, Luis Salazar, Nicolas Saavedra, Pamela Seron, Fernando Lanas, Cristina Moreno Fajardo, Mario Hiroyuki Hirata, Rosario Dominguez Crespo Hirata, and Alvaro Cerda declare no conflicts of interest.

Funding

This investigation was supported by grants from FONDECYT-Chile (N° 11150445), Universidad de La Frontera-Chile (DIUFRO # DI15-0017), and CNPq-Brazil (# 462778/2014-2).

Ethical approval and informed consent

The study protocol was approved by the ethics committee of the Universidad de La Frontera (Protocol # 050/14). All individuals were informed about the study protocol and signed the informed consent form.

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Manriquez, V., Aviles, J., Salazar, L. et al. Polymorphisms in Genes Involved in the Leptin-Melanocortin Pathway are Associated with Obesity-Related Cardiometabolic Alterations in a Southern Chilean Population. Mol Diagn Ther 22, 101–113 (2018). https://doi.org/10.1007/s40291-017-0306-8

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