Cardiometabolic Risk Markers in Children With Obesity and Variants in Pathway-related Genes.

Context: Variants in melanocortin 4 receptor () pathway-related genes have been associated with obesity. The association of these variants with cardiometabolic parameters are not fully known.

Objective: We compared the severity of obesity and cardiometabolic risk markers in children with pathway-related clinically reported genetic variants relative to children without these variants.

Methods: A retrospective chart review was performed in children with obesity who underwent multigene panel testing for monogenic obesity.

Results: Data on a total of 104 children were examined, with 93 (89%) identified as White. Thirty-nine (37.5%) patients had clinically reported variants in the pathway, and the remaining 65 patients did not have reported pathway-related variants. Among the -related variants, risk alleles were most common, reported in 15 children (14%). The maximum body mass index percent of the 95th percentile was not different between groups ( = .116). Low-density lipoprotein cholesterol (LDL-C) was not different between groups ( = .132). However, subgroup analysis demonstrated higher LDL cholesterol in children with the c.661A>G risk allele relative to those with related variant of uncertain significance ( = .047), negative genetic testing ( = .012), and those with non-M related variants ( = .048). The blood pressure, fasting glucose, hemoglobin A1C, total cholesterol, alanine transaminase, and high-density lipoprotein cholesterol were not different between groups.

Conclusion: Variants in the pathway-related genes were not associated with severity of obesity and cardiometabolic risk markers except for the c.661A>G risk allele, which was associated with higher LDL-C levels.