Functional annotation of lactase gene and its distal enhancer MCM6 for prediction of metabolically unhealthy obesity

Abstract

Introduction: Lactose maldigestion associated with single nucleotide variants (SNV) of the genes for lactase (LCT) and its enhancer minichromosome maintenance complex component 6 (MCM6) is one of the key triggers that initiate meta-inflammation in metabolically unhealthy obesity (MUO). The aim is to study the contribution of LCT and MCM6 gene SNV to the development of MUO in children. Material and methods: 152 obese children aged 6–18 years were genotyped for the LCT/MCM6 genes (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) consisted of children with metabolically healthy obesity. Whole genome sequencing (NGS, CeGat, Germany) was performed in 27 children of the main and 15 children of the control group. To verify the results, bioinformatics analysis, analysis of nominal data, calculation of Cramer’s criterion (V), Pearson’s randomness factor (C), and the normalized value of Pearson’s coefficient (C’) were used. Results: Among obese children 20 SNV LCT and 11 SNV MCM6 were revealed. Odds ratio (OR) for MUO to detect SNV LCT A/G rs3213891 – 1.75 (95% CI 0.17–18.4); G/A rs3213890 –2.5 (95% CI 0.65–10.06); C/T rs3754689 – 3.4 (95% CI 1–13.6). SNV MCM6 G/A rs1057031 – OR = 2.6 (95% CI 0.65–10). There is a direct correlation between MUO and SNV LCT with genotypes: A/G rs3213891 (V = 0.073; C = 0.072; C’ = 0.102); G/A rs3213890 (V = 0.284; C = 0.273; C’ = 0.386); C/T rs3754689 (V = 0.278; C = 0.268; C’ = 0.379) and SNV MCM6 G/A rs1057031 (V = 0.143; C = 0.142; C’ = 0.201), p < 0.05. Conclusions: The greatest contribution to the development of MUO in children out of 20 SNV of the LCT gene identified by us in obesity was found for the three genotypes A/G rs3213891, G/A rs3213890, C/T rs3754689, and SNV MCM6 G/A rs1057031 out of 11 SNV MCM6 diagnosed by us.