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Published on: February 2, 2017
Cardiometabolic Risk Markers in Children With Obesity and Variants in MC4R Pathway-related Genes
Mostafa Salama1, Filippo Pinto E Vairo2, Roland Hentz3
1Division of Pediatric Endocrinology and Metabolism, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
Insights
Genetic variants in the melanocortin 4 receptor (MC4R) pathway are linked to obesity. While generally not associated with cardiometabolic risk, the PCSK1 c.661A>G variant was linked to higher LDL cholesterol in children.
Area of Science:
- Genetics
- Pediatrics
- Metabolic Health
Background:
- Melanocortin 4 receptor (MC4R) pathway gene variants are associated with obesity.
- The impact of these variants on cardiometabolic parameters in children is not fully understood.
Purpose of the Study:
- To compare obesity severity and cardiometabolic risk markers in children with and without MC4R pathway-related genetic variants.
Main Methods:
- Retrospective chart review of 104 children with obesity who underwent multigene panel testing for monogenic obesity.
- Comparison of obesity severity (BMI percentile) and cardiometabolic risk markers between groups with and without MC4R pathway variants.
Main Results:
- No significant difference in maximum BMI percentile between groups.
- Low-density lipoprotein cholesterol (LDL-C) levels were not significantly different overall.
- Children with the PCSK1 c.661A>G risk allele showed higher LDL-C compared to other groups.
Conclusions:
- MC4R pathway variants are not generally associated with obesity severity or most cardiometabolic risk markers in children.
- The PCSK1 c.661A>G variant is an exception, linked to elevated LDL-C levels.
Context:
Variants in melanocortin 4 receptor (MC4R) 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 MC4R 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 MC4R pathway, and the remaining 65 patients did not have reported MC4R pathway-related variants. Among the MC4R-related variants, PCSK1 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 (P = .116). Low-density lipoprotein cholesterol (LDL-C) was not different between groups (P = .132). However, subgroup analysis demonstrated higher LDL cholesterol in children with the PCSK1 c.661A>G risk allele relative to those with MC4R-related variant of uncertain significance (P = .047), negative genetic testing (P = .012), and those with non-MC4R related variants (P = .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 MC4R pathway-related genes were not associated with severity of obesity and cardiometabolic risk markers except for the c.661A>G PCSK1 risk allele, which was associated with higher LDL-C levels.
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