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.

Association of PCSK1 and PPARG1 Allelic Variants with Obesity and Metabolic Syndrome in Mexican Adults

“…These results are consistent with other studies; for example, in the Chinese population, an allelic variant of PCSK1 rs6234 was associated with increased BMI and waist circumference [25,26], and, in the young European-American population, these SNPs were associated with increased BMI [27]. Similar results were found in British and Mexican subjects [28,29]. The increase in BMI, weight, waist circumference, and HR associated with the PCSK1 SNP in this population could be because this SNP is strongly associated with obesity due to alterations in thermogenesis and feeding, among other metabolic changes, increasing the anthropometric characteristics mentioned above [26].…”

Associations between polymorphisms in leptin and leptin receptor genes and colorectal cancer survival

“…Furthermore, our study is the first to demonstrate that red meat intake and BMI status may modulate the relationships between LEPR rs7602 or LEPR rs1171278 and CRC survival. Although the mechanisms underlying the observed interactions are not yet fully understood, the positive associations among red meat intake, BMI, and LEP levels, as demonstrated in previous research 45,46 , may provide an explanation. In addition, we surmised that the influence of subtle differences among genotypes was overwhelmed by the detrimental effects of overweight/obesity or high red meat consumption on cancer outcomes.…”

Unravelling variant-to-function relationships in sporulation efficiency through integrative analysis of SNP-specific gene expression networks and metabolic models

“…Several studies have reported complex genetic interactions between identified SNPs in metabolic diseases [35,36]. A recent study has used GWAS variant data to develop personalized organ-specific metabolic models for 524,615 individuals of the INTERVAL and UK Biobank cohorts to clarify the impact of genetic variations on the metabolic processes implicated in coronary artery disease [37].…”