Children’s Nutrition Research Center Staff Publications
Language
English
Publication Date
8-4-2022
Journal
The American Journal of Clinical Nutrition
DOI
10.1093/ajcn/nqac091
PMID
35460232
PMCID
PMC9348975
PubMedCentral® Posted Date
4-23-2022
PubMedCentral® Full Text Version
Post-print
Abstract
Background: Glycine 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.
Objectives: We sought to determine the genomic influence on the serine-glycine ratio in 803 Hispanic children from 319 families of the Viva La Familia cohort.
Methods: We 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.
Results: All 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.
Conclusions: Our study suggests that ALDH1L1 and GLDC SNPs influence the serine-to-glycine ratio and metabolic disease risk.
Keywords
Child, Genome-Wide Association Study, Glycine, Glycine Dehydrogenase (Decarboxylating), Hispanic or Latino, Humans, Insulin Resistance, Oxidoreductases Acting on CH-NH Group Donors, Serine, aldehyde dehydrogenase 1 family member l1, glycine decarboxylase, serine hydroxymethyltransferase, genome-wide association, heritability, adiposity, insulin sensitivity, inflammation, metabolic diseases
Published Open-Access
yes
Recommended Citation
Krupenko, Sergey A; Cole, Shelley A; Hou, Ruixue; et al., "Genetic Variants in ALDH1L1 and Gldc Influence the Serine-to-Glycine Ratio in Hispanic Children" (2022). Children’s Nutrition Research Center Staff Publications. 274.
https://digitalcommons.library.tmc.edu/staff_pub/274
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Dietetics and Clinical Nutrition Commons, Endocrinology, Diabetes, and Metabolism Commons, Nutrition Commons