Association between SNPs in Leptin Pathway Genes and Anthropometric, Biochemical, and Dietary Markers Related to Obesity

Abstract

Obesity is one of the main public health problems in Mexico and the world and one from which a large number of pathologies derive. Single nucleotide polymorphisms (SNPs) of various genes have been studied and proven to contribute to the development of multiple diseases. SNPs of the leptin pathway have been associated with the control of hunger and energy expenditure as well as with obesity and type 2 diabetes mellitus. Therefore, the present work focused on determining the association between anthropometric markers and biochemical and dietary factors related to obesity and SNPs of leptin pathway genes, such as the leptin gene (LEP), the leptin receptor (LEPR), proopiomelanocortin (POMC), prohormone convertase 1 (PCSK1), and the melanocortin 4 receptor (MC4R). A population of 574 young Mexican adults of both sexes, aged 19 years old on average and without metabolic disorders previously diagnosed, underwent a complete medical and nutritional evaluation, biochemical determination, and DNA extraction from the blood; DNA samples were subsequently genotyped. Association analyses between anthropometric, biochemical, and dietary variables with SNPs were performed using binary logistic regressions (p-value = 0.05). Although the sampled population did not have previously diagnosed diseases, the evaluation results showed that 33% were overweight or obese according to BMI and 64% had non-clinically elevated levels of body fat. From the 74 SNP markers analyzed from the five previously mentioned genes, 62 showed polymorphisms within the sampled population, and only 35 of these had significant associations with clinical variables. The risk associations (OR > 1) occurred between clinical markers with elevated values for waist circumference, waist−height index, BMI, body fat percentage, glucose levels, insulin levels, HOMA-IR, triglyceride levels, cholesterol levels, LDL-c, low HDL-c, carbohydrate intake, and protein intake and SNPs of the LEP, LEPR, PCSK1, and MC4R genes. On the other hand, the protective associations (OR < 1) were associated with markers including elevated values for insulin, HOMA-IR, cholesterol, c-LDL, energy intake > 2440 Kcal/day, and lipid intake and SNPs of the LEP and LEPR genes and POMC. The present study describes associations between SNPs in leptin pathway genes, revealing positive and negative interactions between reported SNPs and the clinical markers related to obesity in a sampled Mexican population. Hence, our results open the door for the further study of new genetic variants and their influence on obesity.

Keywords: leptin pathway; obesity; single nucleotide polymorphism.

Figure 1

Classical leptin–melanocortin pathway. The melanocortin pathway is regulated by the production of leptin (LEP) and its receptor (LEPR) present in neurons of the arcuate nucleus of the hypothalamus. LEP induces the expression of proopiomelanocortin (POMC) by activating the JAK-STAT pathway, which is transported by cellular cisterns and degraded by specific enzymes present in the cell, including prohormone convertase 1 (PCSK1, PC1/3), which promotes the formation of α and β melanocyte-stimulating hormones (α/β-MSH) and which are recognized by the melanocortin 4 receptor (MC4R) present in neurons of the paraventricular nucleus of the hypothalamus, which induces the sensation of satiety and increased energy use.

Figure 2

Prevalence of anthropometric markers in the population. (A) The corporal mass distribution according to waist circumference is shown. (B) shows the distribution of body fat according to the waist-hip ratio. (C) shows the percentage of the population at risk of cardiovascular disease according to the waist-to-height ratio. (D) The percentage of the population with low weight, normal weight, overweight, and obesity according to BMI is shown. (E) shows the prevalence of low, normal, and high body fat.