Single Nucleotide Polymorphisms in the Arginase 1 and 2 Genes Are Differentially Associated with Circulating l-Arginine Concentration in Unsupplemented and l-Arginine-Supplemented Adults

TY - JOUR

T1 - Single Nucleotide Polymorphisms in the Arginase 1 and 2 Genes Are Differentially Associated with Circulating l-Arginine Concentration in Unsupplemented and l-Arginine-Supplemented Adults

AU - Hannemann, Juliane

AU - Rendant-Gantzberg, Leonard

AU - Zummack, Julia

AU - Hillig, Jonas

AU - Eilermann, Ina

AU - Böger, Rainer

N1 - © The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.

PY - 2021/4/8

Y1 - 2021/4/8

N2 - BACKGROUND: Genetic variation in arginase may underlie variability in whole blood l-arginine concentrations in unsupplemented and l-arginine-supplemented adults.OBJECTIVES: We aimed to study whether single nucleotide polymorphisms (SNPs) in the arginase 1 (ARG1) and arginase 2 (ARG2) genes are associated with blood l-arginine concentrations in unsupplemented and l-arginine-supplemented individuals.METHODS: In 374 adults (mean ± SD age: 59.6 ± 14.6 y; 180 males), we analyzed SNPs in the ARG1 (rs2246012 and rs2781667) and ARG2 genes (rs3742879 and rs2759757) and their associations with blood l-arginine concentrations. We analyzed associations of haplotypes for the ARG1 gene and for the ARG1 and ARG2 genes combined with blood l-arginine concentrations in supplement users and unsupplemented participants.RESULTS: Of study participants, 120 had low (<42 μmol/L), 133 had medium (42-114 μmol/L), and 121 had high blood l-arginine concentrations (>114 μmol/L); 58 individuals were current l-arginine supplement users. We found a significantly higher prevalence of the minor allele of ARG1 rs2246012 in supplement users with higher blood l-arginine concentrations (P = 0.03). Mean ± SEM l-arginine concentration was 263 ± 9.76 μmol/L in supplement users homozygous for the minor allele of ARG1 rs2246012 (P = 0.004); it was 70.4 ± 25.6 μmol/L in unsupplemented participants homozygous for the minor allele of ARG2 rs3759757 (P = 0.03). The ARG1 haplotype was significantly associated with blood l-arginine concentrations in supplement users (P = 0.046), whereas the combined ARG1/ARG2 haplotype was significantly associated with blood l-arginine concentrations in the cohort as a whole (P = 0.012).CONCLUSIONS: Genetic variability in the ARG1 and ARG2 genes is associated with blood l-arginine concentrations in humans: ARG1 is associated with blood l-arginine concentrations in l-arginine supplement users, whereas ARG2 is associated with blood l-arginine concentrations in unsupplemented participants. Our study is the first to describe a possible functional relation between ARG1 and ARG2 SNPs and blood l-arginine concentrations; genetic variability in ARG1 may explain variation in blood l-arginine concentrations during supplement use and discrepant study results.

AB - BACKGROUND: Genetic variation in arginase may underlie variability in whole blood l-arginine concentrations in unsupplemented and l-arginine-supplemented adults.OBJECTIVES: We aimed to study whether single nucleotide polymorphisms (SNPs) in the arginase 1 (ARG1) and arginase 2 (ARG2) genes are associated with blood l-arginine concentrations in unsupplemented and l-arginine-supplemented individuals.METHODS: In 374 adults (mean ± SD age: 59.6 ± 14.6 y; 180 males), we analyzed SNPs in the ARG1 (rs2246012 and rs2781667) and ARG2 genes (rs3742879 and rs2759757) and their associations with blood l-arginine concentrations. We analyzed associations of haplotypes for the ARG1 gene and for the ARG1 and ARG2 genes combined with blood l-arginine concentrations in supplement users and unsupplemented participants.RESULTS: Of study participants, 120 had low (<42 μmol/L), 133 had medium (42-114 μmol/L), and 121 had high blood l-arginine concentrations (>114 μmol/L); 58 individuals were current l-arginine supplement users. We found a significantly higher prevalence of the minor allele of ARG1 rs2246012 in supplement users with higher blood l-arginine concentrations (P = 0.03). Mean ± SEM l-arginine concentration was 263 ± 9.76 μmol/L in supplement users homozygous for the minor allele of ARG1 rs2246012 (P = 0.004); it was 70.4 ± 25.6 μmol/L in unsupplemented participants homozygous for the minor allele of ARG2 rs3759757 (P = 0.03). The ARG1 haplotype was significantly associated with blood l-arginine concentrations in supplement users (P = 0.046), whereas the combined ARG1/ARG2 haplotype was significantly associated with blood l-arginine concentrations in the cohort as a whole (P = 0.012).CONCLUSIONS: Genetic variability in the ARG1 and ARG2 genes is associated with blood l-arginine concentrations in humans: ARG1 is associated with blood l-arginine concentrations in l-arginine supplement users, whereas ARG2 is associated with blood l-arginine concentrations in unsupplemented participants. Our study is the first to describe a possible functional relation between ARG1 and ARG2 SNPs and blood l-arginine concentrations; genetic variability in ARG1 may explain variation in blood l-arginine concentrations during supplement use and discrepant study results.

U2 - 10.1093/jn/nxaa325

DO - 10.1093/jn/nxaa325

M3 - SCORING: Journal article

C2 - 33232463

VL - 151

SP - 763

EP - 771

JO - J NUTR

JF - J NUTR

SN - 0022-3166

IS - 4

ER -