妊娠糖尿病（GDM）发病率逐年增加。研究提示，高胆固醇摄入（≥300mg/d）增加GDM的风险，胆固醇代谢相关的遗传背景可能和膳食摄入交互作用影响代谢表型，与GDM存在潜在关联。申请者调查发现，我国城市孕妇胆固醇的平均摄入330mg/d，超过300mg/d的孕妇高达54%。但是，中国人群胆固醇摄入、相关的遗传背景以及代谢表型与GDM的关系及相关机制均未阐明。因此，本项目在大样本前瞻性队列的基础上，采用巢式病例对照研究设计，经信度效度验证的FFQ评估膳食胆固醇摄入，新一代中通量基因分型分析胆固醇代谢相关基因多态性，GC-MS检测胆固醇代谢标志物，深入分析胆固醇摄入、代谢基因多态性和代谢标志物水平与GDM的关联以及营养-基因的交互作用。同时选取与GDM存在显著关联的基因，运用慢病毒感染肝细胞构建差异表达模型探讨糖代谢相关的分子机制，为实现GDM的早期预测、精准防治和科学膳食指导提供重要依据。

Gestational diabetes mellitus (GDM), defined as glucose intolerance with onset or first recognition during pregnancy, is a growing health concern. Previous studies in western population indicated that high cholesterol intake (≥300mg/d) was associated with elevated risk of GDM. Meanwhile, gene polymorphisms of cholesterol metabolism related genes (ABCA1, ABCG5/8 and NPC1L1, et al) may interact with dietary factors and implicates a potential association with GDM. Our previous study observed that the average dietary cholesterol intake of Chinese urban pregnant women was 330 mg/d, with 54% of pregnant women having dietary cholesterol intake ≥300 mg/d. However, studies linking dietary cholesterol intake, genetic background, and biomarker levels of cholesterol metabolism to risk of GDM in Chinese population are sparse. Therefore, we will conduct a nested case-control study (including 800 GDM cases and 1600 controls matched for age, pre-pregnancy BMI, et al) to investigate the associations of dietary cholesterol intake, cholesterol metabolism biomarkers, single nucleotide polymorphisms (SNPs) of cholesterol metabolism related genes, and gene-diet interactions with risk of GDM in a birth cohort. Additionally, lentivirus-mediated overexpression or shRNA interference of target genes will be transfected into HepG2 cells to investigate the underlying mechanisms. The results of our study will provide important clues for early prediction, personalized dietary guidance, and evidence-based prevention for GDM.