School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, P. R. China.
Department of Clinical Nutrition, Haidian Maternal and Child Health Hospital, Beijing 100080, P. R. China.
J Clin Endocrinol Metab. 2022 Jul 14;107(8):e3134-e3144. doi: 10.1210/clinem/dgac317.
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.
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.
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.
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.
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.
母体和胎儿脂质代谢基因单核苷酸多态性（SNP）与母体超生理高胆固醇血症（MSPH）风险的联合关联尚不清楚。
本研究旨在探讨 APOE、LPL、LDLR、PCSK9 和 SCARB1 基因的母体/胎儿 SNP 与 MSPH 风险的相关性，并探讨风险等位基因的母体-胎儿配对模式是否会影响 MSPH 风险。
进行了一项嵌套病例对照研究，纳入了 182 例 MSPH 孕妇和 182 例母体生理性高胆固醇血症孕妇。采集母体静脉和脐静脉血检测基因 SNP。主要结局为 MSPH。采用 logistic 回归模型确定 SNP 与 MSPH 风险的相关性。
母体 APOE rs429358 T > C（调整后的优势比[OR] = 1.72，P = 0.033）的 C 等位基因、胎儿 APOE rs440446 C > G（调整后的 OR = 1.62，P = 0.012）的 G 等位基因和胎儿 LPL rs263 C > T（调整后的 OR = 1.53，P = 0.011）的 T 等位基因增加了 MSPH 的风险。母体 LDLR rs7258950 G > A（调整后的 OR = 0.67，P = 0.028）的 A 等位基因降低了 MSPH 的风险。对于母体-胎儿配对分析，PCSK9 rs2149041、rs7523141、rs7523242、rs7525649 和 LDLR rs7258950 的变异一致性在显性模型下与 MSPH 风险降低相关。其他 PCSK9、APOE、LDLR、LPL 和 SCARB1 基因的 SNP 变异一致性与 MSPH 风险增加相关。
本研究支持母体和胎儿脂质代谢基因遗传多态性与 MSPH 风险相关的假设。母体-胎儿变异一致性也与这种风险相关。
