What is the effect of maternal circulating amino acids on offspring birthweight? TheLancet BristolUni Cambridge_Uni aminoacid maternalhealth birthweight
By Neha MathurFeb 27 2023Reviewed by Danielle Ellis, B.Sc. In a recent study published in the eBioMedicine, researchers examined the effect of serum levels of 20 amino acids in a mother during pregnancy on offspring birthweight in a two-sample summary data Mendelian randomization framework.
It is also noteworthy that previous studies have found that branched-chain amino acids , including valine, leucine, and isoleucine, cross the placenta more rapidly using sodium-independent L system, and their high concentrations in maternal serum lead to a higher risk of intrauterine growth-restricted pregnancies. Previous studies have used the MR approach to confirm the causal effect of maternal smoking during pregnancy on slower fetal growth.
The team used the weighted linear model adjusted analyses, an approximation of the structural equation modeling approach developed by Warrington et al., to adjust for offspring genetic effects in the summary data used to evaluate the association of maternal genetic variants on offspring birthweight. Likewise, they estimated associations between genetic variants and amino acids.
Next, the team natural log-transformed amino acid levels, winsorized at five standard deviations and transformed to Z scores, then adjusted for maternal age and top 10 principal components from genomic data, e.g., minor allele frequency . Then, they regressed each resulting residual against the corresponding SNP used in the primary MR analysis. This exercise yielded 89 SNP-amino acid associations.
While the genetic variant rs2657879 had a strong positive effect, the effect instrumented by rs7587672, an expression quantitative trait loci for GLS, this effect turned inverse. Note that GLS2 encodes the catalyst that helps convert glutamine to ammonia and glutamate in the liver, whereas GLS encodes the kidney-type isozyme.
Studies have proposed that leucine amino acid modulates fetal muscle protein synthesis through mammalian target of the rapamycin signaling pathway. Accordingly, maternal circulating leucine had an inverse effect on offspring birthweight in the primary MR analysis. In contrast to findings of previous studies, researchers found higher maternal circulating BCAAs had a negative association with offspring birthweight.
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