ArticleThe American journal of clinical nutrition2022
Genetic variants in ALDH1L1 and GLDC influence the serine-to-glycine ratio in Hispanic children.
Article in The American journal of clinical nutrition, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 7 citations in OpenAlex.
- Plasma serine and glycine in relation to clinical outcomes following neoadjuvant radiotherapy for rectal cancer.Clinical and translational radiation oncology · 2026Article
- Impact of DNA methylation on digestive and metabolic gene expression in red pandas (Ailurus fulgens) during the transition from milk to bamboo diet.BMC genomics · 2025Article
- Untargeted Metabolomics Reveals Dysregulation of Glycine- and Serine-Coupled Metabolic Pathways in an ALDH1L1-Dependent Manner In Vivo.Metabolites · 2024Article
- Targeting one-carbon metabolism for cancer immunotherapy.Clinical and translational medicine · 2024Review
- Exploratory Metabolomics Underscores the Folate Enzyme ALDH1L1 as a Regulator of Glycine and Methylation Reactions.Molecules (Basel, Switzerland) · 2022Article
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Authors and funding
9 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundGlycine is a proteogenic amino acid that is required for numerous metabolic pathways, including purine, creatine, heme, and glutathione biosynthesis. Glycine formation from serine, catalyzed by serine hydroxy methyltransferase, is the major source of this amino acid in humans. Our previous studies in a mouse model have shown a crucial role for the 10-formyltetrahydrofolate dehydrogenase enzyme in serine-to-glycine conversion.
objectivesWe sought to determine the genomic influence on the serine-glycine ratio in 803 Hispanic children from 319 families of the Viva La Familia cohort.
methodsWe performed a genome-wide association analysis for plasma serine, glycine, and the serine-glycine ratio in Sequential Oligogenic Linkage Analysis Routines while accounting for relationships among family members.
resultsAll 3 parameters were significantly heritable (h2 = 0.22-0.78; P < 0.004). The strongest associations for the serine-glycine ratio were with single nucleotide polymorphisms (SNPs) in aldehyde dehydrogenase 1 family member L1 (ALDH1L1) and glycine decarboxylase (GLDC) and for glycine with GLDC (P < 3.5 × 10-8; effect sizes, 0.03-0.07). No significant associations were found for serine. We also conducted a targeted genetic analysis with ALDH1L1 exonic SNPs and found significant associations between the serine-glycine ratio and rs2886059 (β = 0.68; SE, 0.25; P = 0.006) and rs3796191 (β = 0.25; SE, 0.08; P = 0.003) and between glycine and rs3796191 (β = -0.08; SE, 0.02; P = 0.0004). These exonic SNPs were further associated with metabolic disease risk factors, mainly adiposity measures (P < 0.006). Significant genetic and phenotypic correlations were found for glycine and the serine-glycine ratio with metabolic disease risk factors, including adiposity, insulin sensitivity, and inflammation-related phenotypes [estimate of genetic correlation = -0.37 to 0.35 (P < 0.03); estimate of phenotypic correlation = -0.19 to 0.13 (P < 0.006)]. The significant genetic correlations indicate shared genetic effects among glycine, the serine-glycine ratio, and adiposity and insulin sensitivity phenotypes.
conclusionsOur study suggests that ALDH1L1 and GLDC SNPs influence the serine-to-glycine ratio and metabolic disease risk.
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