Associations between a common variant near the MC4R gene and serum triglyceride levels in an obese pediatric cohort

Abstract

Polymorphisms near the MC4R gene may be related to an increased risk for obesity, but studies of variations in this gene and its relation to cardiometabolic profiles and food intake are scarce and controversial. The aim of this study is to evaluate the influence of the variants rs12970134 and rs17782313 near the MC4R gene in food intake, binge eating (BE) behavior, anthropometric parameters, body composition, metabolic profile, and cardiometabolic risk factors in obese children and adolescents. This is a cross-sectional study that included obese children and adolescents. We evaluated anthropometric, metabolic parameters and cardiometabolic risk factors, including hypertension, impaired fasting glucose, hypertriglyceridemia, and low HDL-cholesterol. BE was assessed through the BE scale, and a 24-h recall was used to evaluate total caloric intake and percentage of macronutrients and types of dietary fat. The MC4R variants rs12970134 and rs17782313 were genotyped using TaqMan assay. To assess the magnitude of risk, a logistic regression adjusted for Z-BMI, age, and gender was performed, adopting the significance level of 0.05. The study included 518 subjects (52.1 % girls, 12.7 ± 2.7 years old, Z-BMI = 3.24 ± 0.57). Carriers of the variant rs17782313 exhibit increased triglyceride levels (108 ± 48 vs. 119 ± 54, p = 0.034) and an increased risk of hypertriglyceridemia (OR 1.985, 95 % CI 1.288-3.057, p = 0.002). There was no association of the SNP rs12970134 with clinical, metabolic, or nutritional parameters. The variant rs12970134 and rs17782313 did not influence food intake or the presence of BE. The variant rs17782313 is associated with an increased risk of hypertriglyceridemia in obese children and adolescents.

Melanocortin-4 Receptor and Lipocalin 2 Gene Variants in Spanish Children with Abdominal Obesity: Effects on BMI-SDS after a Lifestyle Intervention

“…Heterozygous subjects for the Ile251Leu SNP showed higher levels of total cholesterol and LDL-cholesterol. There are studies on the association between MC4R variants and other lipid markers in several populations [31,46].…”

Rs12970134 near MC4R is associated with appetite and beverage intake in overweight and obese children: A family-based association study in Chinese population

“…In fact, different genetic models have been used in previous studies, including the dominant model [57], the recessive model [58], and the additive model [59], and there are no conclusions yet which genetic model is the best. However, when investigating at the characterization of the MC4R knock-out mice, Cone, et al found that animals heterozygous for the melanocortin-4 receptor were intermediate to wild type and MC4R null mice in obesity-related phenotypes including growth rate, serum leptin concentrations, linear growth, and fasting serum insulin concentrations [45].…”

DNA methylations of MC4R and HNF4α are associated with increased triglyceride levels in cord blood of preterm infants

“…[50] To date, very few studies have been conducted to investigate the association between DNA methylation of MC4R and metabolic components in cord blood, although most genetic studies have shown that common variants near MC4R were associated with elevated TG levels and an increased risk of hypertriglyceridemia in obese children and adolescents. [51] In addition, genetic variants of MC4R have been found to lead to substantially higher postprandial response of TG levels in healthy subjects. [52] The active forms of MC4R decrease the activity of stearoyl-coenzyme A desaturase 1, which is involved in TG synthesis and affects LDL levels via the liver, resulting in decreased TG synthesis.…”