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.