Single Nucleotide Variants of the MCM6 Gene as a Risk Factor for Metabolically Unhealthy Obesity in Children

Abstract

BackgroundLactose maldigestion associated with lactase non-persistence is a trigger for persistent meta-inflammation in metabolically unhealthy obesity (MUO), including arterial hypertension, atherogenic-type dyslipidemia, and insulin resistance. Aimto study the contribution of single nucleotide variants (SNV) of the gene minichromosome maintenance complex component 6 (MCM6) to the development of MUO in children. Materials and methods. 152 obese children aged 6-18 years were genotyped for the MCM6 gene (RT-PCR, Synevo, Ukraine). The main group (n=77) according to the IDEFICS 2014 recommendations was represented by children with MUO. The control group (n=75) consolidated of children with metabolically obesity (MHO). Additionally, whole genome sequencing (NGS, CeGat, Germany) was performed in 27 children of the main and 15 children of the control group. Verification of results: odds ratio (OR) estimate, 95% confidence interval (CI), calculation of Spearman's correlation coefficient (r) and p-value for each variable. ResultsAmong obese children, 11 MCM6 SNVs were identified (rs61752701, rs141448886, rs201537325, rs2289049, rs3087353, rs1057031, rs143348934, rs3087348, rs4988270, rs2070068). The frequency of MUO (r=0.22; p=0.020) and extreme obesity (r=0.22; p=0.022) was higher in children with with the "wild" genotype MCM6-13910 and was respectively OR 80.0; 95% CI 66.96 - 88.76 and OR 54.0%; 95% CI 40.4 - 67.03, compared with with carriers of mutant genotypes (r=-0,37; р<0,001). OR at MUO to detect SNV MCM6 G/A rs105703 - 2.6 95% СI 0.65-10. ConclusionsThe greatest contribution to the development of MUO in children is made by the G/A rs1057031 genotype out of 11 SNV MCM6 diagnosed by us.