Repositorio
Institucional

Cerda, Alvaro

Manriquez, Victor#Aviles, Jorge#Salazar, Luis#Saavedra, Nicolas#Seron, Pamela#Lanas, Fernando#Fajardo, Cristina Moreno#Hirata, Mario Hiroyuki#Crespo Hirata, Rosario Dominguez

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

ADIS INT LTD

MOLECULAR DIAGNOSIS & THERAPY

en

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/m(2)), overweight (BMI 25.0-29.9 kg/m(2)), and obese (BMI C 30 kg/m(2)) 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/m(2) 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/m(2) (p < 0.05). Regarding lipid profile, LEPR rs1137101 allele G carriers had lower triglycerides and very-lowdensity 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 population.

Artículo original

This investigation was supported by grants from FONDECYT-Chile (No 11150445), Universidad de La Frontera-Chile (DIUFRO # DI15-0017), and CNPq- Brazil (# 462778/2014-2).

Esta investigación fue apoyada por subvenciones de FONDECYT-Chile (No 11150445), Universidad de La Frontera-Chile (DIUFRO

DI15-0017) y CNPq-Brasil (

462778/2014-2).

This investigation was supported by grants from FONDECYT-Chile (No 11150445), Universidad de La Frontera-Chile (DIUFRO

DI15-0017), and CNPq- Brazil (

10.1007/s40291-017-0306-8

pdf

http://dx.doi.org/10.1007/s40291-017-0306-8

Genetics & Heredity# Pharmacology & Pharmacy

Genética y Herencia

Fisiología

Endocrinología y Metabolismo (Incluye Diabetes, Hormonas)

WOS:000422910300008

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

Artículo original

version publicada

ADIS INT LTD

MOLECULAR DIAGNOSIS & THERAPY

Genética y Herencia# Farmacología y farmacia

1177-1062

en

ANID FONDECYT 11150445#UFRO DI15-0017#CNPq 462778/2014-2

ANID FONDECYT 11150445

URO DI15-0017

CNPq 462778/2014-2

This investigation was supported by grants from FONDECYT-Chile (No 11150445), Universidad de La Frontera-Chile (DIUFRO # DI15-0017), and CNPq- Brazil (# 462778/2014-2).

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