Prenatal Chromium Exposure and Gestational Diabetes Mellitus: Integrating Genetic and Epigenetic Regulation of LPCAT1 from a Phospholipid Remodeling Perspective.

Abstract

The trace element chromium (Cr) has been implicated in the risk of gestational diabetes mellitus (GDM), the underlying mechanisms remain unclear. Phospholipid remodeling is known to contribute to insulin regulation and may serve as a potential intermediate link between Cr exposure and GDM risk. Lysophosphatidylcholine acyltransferase 1 (LPCAT1), as an important regulatory factor in phospholipid remodeling, may play a certain role in this process. For the first time, this study investigates the relationship between Cr exposure and GDM risk from the perspective of phospholipid remodeling, while integrating the genetic predisposition and epigenetic regulation of the LPCAT1 gene. A cohort comprising 107 pregnant women diagnosed with GDM and 107 matched controls without GDM was recruited. Blood samples were collected prior to delivery to perform LPCAT1 genotyping, assess DNA methylation patterns, and quantify Cr concentrations. Elevated Cr levels in maternal blood were significantly correlated with an increased risk of GDM. Furthermore, a multiplicative interaction was observed between Cr exposure and four single nucleotide polymorphisms (SNPs) within the LPCAT1 gene. Three Cr-associated DNA methylation CpG sites were identified in GDM patients. Methylation quantitative trait locus (mQTLs) analysis revealed that three SNPs (rs4371798, rs56358072, rs6554859) were significantly associated with methylation at a specific CpG site (cg22185977) within LPCAT1. These findings suggest that genetic polymorphisms in LPCAT1 may modulate individual susceptibility to Cr exposure and consequent GDM risk by influencing the methylation status of the LPCAT1 gene. This study provides novel etiological insights into the role of Cr in inducing GDM through mechanisms involving phospholipid remodeling.