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

Oct 5, 2017Molecular diagnosis & therapy

Genetic Differences in the Leptin-Melanocortin System Linked to Obesity-Related Heart and Metabolic Issues in Southern Chile

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Abstract

The LEPR rs1137101 GG genotype is associated with a reduced risk of obesity and metabolic syndrome.

The LEPR rs1137101 GG genotype has an odds ratio of 0.26 for obesity and 0.36 for metabolic syndrome, though these findings were not significant after multiple testing corrections.
Carriers of the LEPR rs1137101 G allele exhibited lower body mass index (BMI) and waist-to-hip ratio (WHR), with reductions of 2.44 kg/m and 0.033 units, respectively.
The MC4R rs17782313 C allele is slightly associated with a reduced risk of metabolic syndrome (odds ratio 0.48) and lower BMI values of 1.95 kg/m.
Individuals with the LEPR rs1137101 G allele had lower triglycerides and very-low-density lipoprotein (VLDL) cholesterol levels.
Carriers of the MC4R rs17782313 C allele showed higher high-density lipoprotein (HDL) cholesterol levels.
The LEP rs7799039 A allele is slightly associated with reduced total and low-density lipoprotein (LDL) cholesterol.

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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), overweight (BMI 25.0-29.9 kg/m), and obese (BMI ≥ 30 kg/m) 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. 2 2 2

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/mand 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(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). 2 2

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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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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