Genotype-environment interaction in the formation of lipid profile of adolescents

Many genetic variants associated with metabolic disorders have incomplete penetrance in human. Their phenotypic manifestation depends on the life style factors. In this work, we compared the associations of genotypes at 11 polymorphic sites with body mass index (BMI) and lipid metabolism parameters (levels of total cholesterol (TC), triglycerides, high- and low-density lipoprotein cholesterol (HDL-C and LDL-C)) in three groups of adolescents from Novosibirsk, examined in 1999, 2009 and 2019. In each group, from 187 to 665 persons were genotyped at each site. One-way analysis of variance (independent covariates: gender and age) was used for evaluation. For rs1800497 in the ANKK1 gene, rs53576 in the OXTR gene, rs1360780 in the FKBP5 gene, and rs4680 in the COMT gene, as well as for tandem repeats in the promoter of the MAOA gene, promoter and intron 2 of the SLC6A4 gene (separately and as part of a haplotype), and 3′-untranslated region of the SLC6A3 no associations of genotypes with BMI and lipid metabolism parameters were found in any of the groups. For APOE genotype, an association was obtained with TC levels: p = 0.042 and 0.034, respectively, in the 1999 and 2009 collection groups, as well as with LDL-C: p = 0.001 and 0.002, respectively, in the 2009 and 2019 groups. Moreover, the maximum levels of TC and LDL-C were found among carriers of most common genotype ε3ε3 in 1999 group, and among carriers of atherogenic allele ε4 in other two groups. Thus, it was shown that in adolescents there was an opposite correlation of carriage of the ε4ε4 genotype for the APOE gene with the levels of total cholesterol and LDL cholesterol in the case of normal and reduced calorie intake. For rs6265 in the BDNF gene, the level of statistical significance of the association of the common C allele with TC and LDL-C levels was directly correlated with dietary caloric intake (p = 0.617 and 0.573; p = 0.049 and 0.090; p = 0.010 and 0.024, respectively, in the groups of 1999, 2009 and 2019).

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