Lipid Metabolic Genes and Maternal Supraphysiological Hypercholesterolemia: An Analysis of Maternal-fetal Interaction

Abstract

Abstract Context The joint associations of maternal and fetal single nucleotide polymorphisms (SNPs) of lipid metabolic genes with the risk of maternal supraphysiological hypercholesterolemia (MSPH) are unclear. Objective This study aims to investigate the associations of maternal/fetal SNPs of APOE, LPL, LDLR, PCSK9, and SCARB1 with the risk of MSPH and explore whether the maternal-fetal pairing pattern of the risk alleles can affect MSPH risk. Methods A nested case-control study was conducted that included 182 pregnant women with MSPH and 182 with maternal physiological hypercholesterolemia. Maternal venous and umbilical venous blood were collected to detect the SNPs of genes. The primary outcome was MSPH. Logistic regression model was used to determine the associations of SNPs with risk of MSPH. Results The C-allele in maternal APOE rs429358 T > C (adjusted odds ratio [OR] = 1.72, P = 0.033), G-allele in fetal APOE rs440446 C > G (adjusted OR = 1.62, P = 0.012) and T-allele in fetal LPL rs263 C > T (adjusted OR = 1.53, P = 0.011) increased the risk of MSPH. The A-allele in maternal LDLR rs7258950 G > A decreased the risk of MSPH (adjusted OR = 0.67, P = 0.028). For maternal-fetal pairing analysis, the variant concordance of PCSK9 rs2149041, rs7523141, rs7523242, rs7525649, and LDLR rs7258950 were associated with the decreased risk of MSPH under the dominant model. The variant concordance of other SNPs of PCSK9, APOE, LDLR, LPL, and SCARB1 were associated with the increased risk of MSPH. Conclusion This study supports the hypothesis that maternal and fetal genetic polymorphisms of lipid metabolic genes are associated with the risk of MSPH. The maternal-fetal variant concordance is also associated with this risk.