Cholesterol-rich dietary pattern during early pregnancy and genetic variations of cholesterol metabolism genes in predicting gestational diabetes mellitus: a nested case-control study

Background: Higher dietary cholesterol intake during pregnancy increases risk of gestational diabetes mellitus (GDM). However, no studies have investigated interindividual variability in cholesterol metabolism and the association of genetics and diet on GDM.

Objective: ; To prospectively evaluate the joint association of cholesterol-rich dietary patterns and polymorphisms of genes coding for cholesterol metabolism pathway proteins with GDM.

Methods: A total of 1116 pregnant females from the Tongji Birth Cohort were enrolled. GDM was diagnosed according to a 75-g 2-h oral glucose tolerance test at 24-28 wk of gestation. Dietary data were collected by a validated food frequency questionnaire. The reduced-rank regression method was used to identify dietary patterns using dietary cholesterol as the response variable. Time-of-flight mass spectrometry was used for genotyping. The genetic risk score (GRS) for GDM was constructed with genetic variants in 28 cholesterol metabolism-related single-nucleotide polymorphisms (SNPs). Conditional logistic regression models were used to assess the odds ratio (OR) for GDM.

Results: The cholesterol-rich dietary pattern was rich in livestock and poultry meat and eggs but lower in cereals. The multivariable-adjusted ORs for GDM were 1.24 (95% confidence interval: 1.06-1.44) per SD increment of cholesterol-rich pattern scores and 1.28 (1.09-1.49) per tertile GRS. The variants of the CYP7A1 rs3808607 G→T/rs8192871 G→A/rs7833904 A→T, as well as AGGG and TTGA haplotypes of 4 CYP7A1-spanning SNPs, were significantly associated with GDM. For the joint effect, the OR was 3.53 (1.71-7.31) in the highest categories of both dietary pattern scores and GRS compared with individuals with the lowest strata without significant interaction (P for interaction = 0.101).

Conclusions: Both a cholesterol-rich dietary pattern and genetic variants of cholesterol metabolism genes are associated with risk of GDM. Adherence to a cholesterol-rich dietary pattern during early pregnancy promotes the chance of GDM, especially in women with higher GRS.

Clinical trial registry: This trial was registered at http://www.chictr.org.cn (Registration number: ChiCTR1800016908). URL: =https://www.chictr.org.cn/showprojEN.html?proj=28081.