Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
J Nutr. 2021 Apr 8;151(4):763-771. doi: 10.1093/jn/nxaa325.
Genetic variation in arginase may underlie variability in whole blood l-arginine concentrations in unsupplemented and l-arginine-supplemented adults.
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.
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.
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).
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.
精氨酸酶的遗传变异可能是未补充和补充精氨酸的成年人全血 l-精氨酸浓度变化的基础。
我们旨在研究精氨酸酶 1（ARG1）和精氨酸酶 2（ARG2）基因中的单核苷酸多态性（SNP）是否与未补充和补充精氨酸的个体的血液 l-精氨酸浓度相关。
在 374 名成年人（平均年龄 ± 标准差：59.6 ± 14.6 岁；180 名男性）中，我们分析了 ARG1（rs2246012 和 rs2781667）和 ARG2 基因（rs3742879 和 rs2759757）中的 SNP 及其与血液 l-精氨酸浓度的关系。我们分析了 ARG1 基因和 ARG1 和 ARG2 基因的单倍型与补充剂使用者和未补充剂使用者的血液 l-精氨酸浓度之间的关系。
在研究参与者中，120 人的血液 l-精氨酸浓度较低（<42 μmol/L），133 人的血液 l-精氨酸浓度中等（42-114 μmol/L），121 人的血液 l-精氨酸浓度较高（>114 μmol/L）；58 人是当前的 l-精氨酸补充剂使用者。我们发现，携带 ARG1 rs2246012 次要等位基因的补充剂使用者的血液 l-精氨酸浓度较高，这一现象具有显著的统计学意义（P=0.03）。携带 ARG1 rs2246012 次要等位基因的补充剂使用者的平均 ± SEM 精氨酸浓度为 263 ± 9.76 μmol/L（P=0.004）；携带 ARG2 rs3759757 次要等位基因的未补充剂使用者的平均 ± SEM 精氨酸浓度为 70.4 ± 25.6 μmol/L（P=0.03）。ARG1 单倍型与补充剂使用者的血液 l-精氨酸浓度显著相关（P=0.046），而 ARG1/ARG2 联合单倍型与整个队列的血液 l-精氨酸浓度显著相关（P=0.012）。
ARG1 和 ARG2 基因的遗传变异性与人类血液中的 l-精氨酸浓度相关：ARG1 与 l-精氨酸补充剂使用者的血液 l-精氨酸浓度相关，而 ARG2 与未补充剂使用者的血液 l-精氨酸浓度相关。本研究首次描述了 ARG1 和 ARG2 SNP 与血液 l-精氨酸浓度之间可能存在的功能关系；ARG1 的遗传变异性可能可以解释补充剂使用期间和不同研究结果中血液 l-精氨酸浓度的变化。
