Polymorphisms in the choline transporter SLC44A1 are associated with reduced cognitive performance in normotypic but not prenatal alcohol-exposed children.

Autor:	Smith SM; UNC Nutrition Research Institute University of North Carolina at Chapel Hill, Kannapolis, NC, United States; Department of Nutrition, University of North Carolina at Chapel Hill, Kannapolis, NC, United States. Electronic address: Susan_Smith@unc.edu., Weathers TD; UNC Nutrition Research Institute University of North Carolina at Chapel Hill, Kannapolis, NC, United States., Virdee MS; UNC Nutrition Research Institute University of North Carolina at Chapel Hill, Kannapolis, NC, United States., Schwantes-An TH; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States., Voruganti VS; UNC Nutrition Research Institute University of North Carolina at Chapel Hill, Kannapolis, NC, United States; Department of Nutrition, University of North Carolina at Chapel Hill, Kannapolis, NC, United States., Mattson SN; Center for Behavioral Teratology, San Diego State University, San Diego, CA, United States., Coles CD; Departments of Psychiatry and Behavioral Science and Pediatrics, Emory University School of Medicine, Atlanta, GA, United States., Kable JA; Departments of Psychiatry and Behavioral Science and Pediatrics, Emory University School of Medicine, Atlanta, GA, United States., Sowell E; Department of Pediatrics, Neurology, and Psychology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States., Wozniak JR; Department of Psychiatry & Behavioral Science, University of Minnesota, Minneapolis, MN, United States., Wetherill L; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States.
Jazyk:	angličtina
Zdroj:	The American journal of clinical nutrition [Am J Clin Nutr] 2024 Jan; Vol. 119 (1), pp. 117-126. Date of Electronic Publication: 2023 Nov 27.
DOI:	10.1016/j.ajcnut.2023.10.003
Abstrakt:	Background: Choline is essential for healthy cognitive development. Single nucleotide polymorphisms (SNPs; rs3199966(G), rs2771040(G)) within the choline transporter SLC44A1 increase risk for choline deficiency. In a choline intervention trial of children who experienced prenatal alcohol exposure (PAE), these alleles are associated with improved cognition. Objective: This study aimed to determine if SNPs within SLC44A1 are differentially associated with cognition in children with PAE compared with normotypic controls (genotype × exposure). A secondary objective tested for an association of these SNPs and cognition in controls (genotype-only). Design: This is a secondary analysis of data from the Collaborative Initiative on Fetal Alcohol Spectrum Disorders. Participants (163 normotypic controls, 162 PAE) underwent psychological assessments and were genotyped within SLC44A1. Choline status was not assessed. Association analysis between genotype × exposure was performed using an additive genetic model and linear regression to identify the allelic effect. The primary outcome was the interaction between SLC44A1 genotype × exposure status with respect to cognition. The secondary outcome was the cognitive-genotype association in normotypic controls. Results: Genotype × exposure analysis identified 7 SNPs in SLC44A1, including rs3199966(G) and rs2771040(G), and in strong linkage (D' ≥ 0.87), that were associated (adjusted P ≤ 0.05) with reduced performance in measures of general cognition, nonverbal and quantitative reasoning, memory, and executive function (β, 1.92-3.91). In controls, carriers of rs3199966(GT or GG) had worsened cognitive performance than rs3199966(TT) carriers (β, 0.46-0.83; P < 0.0001), whereas cognitive performance did not differ by rs3199966 genotype in those with PAE. Conclusions: Two functional alleles that increase vulnerability to choline deficiency, rs3199966(G) (Ser644Ala) and rs2771040(G) (3' untranslated region), are associated with worsened cognition in otherwise normotypic children. These alleles were previously associated with greater cognitive improvement in children with PAE who received supplemental choline. The findings endorse that choline benefits cognitive development in normotypic children and those with PAE. (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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