Zhoushan Maternal and Child Care Hospital, Zhoushan, China.
Department of Public Health, and Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Department of Epidemiology & Health Statistics, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China; Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Clin Nutr. 2021 May;40(5):3650-3660. doi: 10.1016/j.clnu.2020.12.029. Epub 2020 Dec 29.
BACKGROUND & AIMS: This study aims to explore the associations of vitamin D (VD) metabolic pathway gene with 25(OH)D level in pregnant women and the interactions of SNP with season and VD supplement.
A total of 2658 pregnant women were selected from Zhoushan Pregnant Women Cohort study. Gestational 25(OH)D level and single nucleotide polymorphism (SNP) of VD metabolic pathway gene were detected. Multilinear regression models were used to estimate associations of SNPs with gestational 25(OH)D levels. Stratified analyses were performed to test the interactions of SNP with season and VD supplements.
The mutations of rs2298849 and rs7041 on the GC gene were respectively associated with higher 25(OH)D in the first and third trimester; the mutations of seven SNPs (rs1155563, rs16846876, rs17467825, rs2282679, rs2298850, rs3755967, and rs4588) on the GC gene were respectively associated with lower 25(OH)D both in the first and third trimester, and lower changes in 25(OH)D during late pregnancy. The mutations of above seven SNPs, except for rs1155563, were also respectively associated with lower 25(OH)D in the second trimester, but to a lesser extent; Besides, pregnant women with mutation on CYP24A1-rs2209314 had a higher increment in 25(OH)D than their counterparts in the second trimester. The increasing dose effect of Gc isoform on 25(OH)D was observed. The associations of GC and LRP2 genes with 25(OH)D modified by season and VD supplements.
The polymorphisms of VD metabolic pathway gene were associated with gestational 25(OH)D, and the associations differ by seasons and VD supplements. Gc isoform exerted a profound influence on gestational 25(OH)D.
本研究旨在探讨维生素 D(VD)代谢途径基因与孕妇 25(OH)D 水平的关联,以及 SNP 与季节和 VD 补充剂的相互作用。
从舟山孕妇队列研究中选择了 2658 名孕妇。检测了孕妇的妊娠 25(OH)D 水平和 VD 代谢途径基因的单核苷酸多态性(SNP)。采用多元线性回归模型估计 SNP 与妊娠 25(OH)D 水平的相关性。进行分层分析以检验 SNP 与季节和 VD 补充剂的相互作用。
GC 基因上的 rs2298849 和 rs7041 突变分别与第一和第三孕期更高的 25(OH)D 水平相关;GC 基因上的 rs1155563、rs16846876、rs17467825、rs2282679、rs2298850、rs3755967 和 rs4588 等七个 SNP 的突变分别与第一和第三孕期的 25(OH)D 水平较低相关,并且妊娠晚期 25(OH)D 的变化也较低。除 rs1155563 外,上述七个 SNP 的突变也分别与第二孕期的 25(OH)D 水平较低相关,但程度较轻;此外,CYP24A1-rs2209314 突变的孕妇在第二孕期 25(OH)D 的增加量高于其对应者。观察到 Gc 同工型对 25(OH)D 的剂量效应增加。GC 和 LRP2 基因与 25(OH)D 的关联受季节和 VD 补充剂的影响。
VD 代谢途径基因的多态性与孕妇的妊娠 25(OH)D 水平相关,并且这种关联因季节和 VD 补充剂而异。Gc 同工型对妊娠 25(OH)D 水平有深远影响。