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单核苷酸多态性 rs3742879 影响先兆子痫患者的血浆精氨酸酶 2 水平、一氧化氮形成和降压治疗反应。

single-nucleotide polymorphism rs3742879 affects plasma arginase 2 levels, nitric oxide formation and antihypertensive therapy response in preeclampsia.

机构信息

Department of Genetics, Ecology & Evolution, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, 31270-901, Brazil.

Department of Biophysics & Pharmacology, Institute of Biosciences of Botucatu, Universidade Estadual Paulista (UNESP), Distrito Rubiao Junior, Botucatu, Sao Paulo, 18618-689, Brazil.

出版信息

Pharmacogenomics. 2022 Aug;23(13):713-722. doi: 10.2217/pgs-2022-0079. Epub 2022 Aug 16.

Abstract

This work examined whether (rs2781659, rs2781667, rs2246012 and rs17599586) and (rs3742879 and rs10483801) single-nucleotide polymorphisms (SNPs) are associated with antihypertensive therapy responsiveness in preeclampsia (PE) and their effects on arginase isoforms and nitrite concentrations in responsive and nonresponsive patients. SNP genotypes were determined by TaqMan assays. Plasma arginase levels were measured by ELISA and nitrite concentrations were measured using an ozone-based chemiluminescence assay. The G allele for rs3742879 (A>G) was less frequent in nonresponsive compared with responsive patients (15.5% vs 24.7%, respectively) and the G carriers of the nonresponsive subgroup had lower arginase 2 (9.2 ± 7.5 ng/ml vs 19.1 ± 17.3 ng/ml) and higher nitrite concentrations (110.2 ± 52.8 nM vs 78.5 ± 37.9 nM) than carriers of the AA genotype (all p < 0.05). SNP rs3742879 is associated with diminished arginase 2 levels and increased nitric oxide formation in nonresponsive PE patients.

摘要

这项工作研究了 rs2781659、rs2781667、rs2246012 和 rs17599586 以及 rs3742879 和 rs10483801 单核苷酸多态性 (SNP) 是否与先兆子痫 (PE) 患者的降压治疗反应性相关,以及它们对反应性和非反应性患者的精氨酸酶同工型和亚硝酸盐浓度的影响。SNP 基因型通过 TaqMan 分析确定。通过 ELISA 测量血浆精氨酸酶水平,通过基于臭氧的化学发光测定法测量亚硝酸盐浓度。与反应性患者相比,非反应性患者的 rs3742879 (A>G) 中的 G 等位基因频率较低(分别为 15.5%和 24.7%),非反应性亚组的 G 携带者的精氨酸酶 2 水平较低(9.2±7.5ng/ml 与 19.1±17.3ng/ml),亚硝酸盐浓度较高(110.2±52.8nM 与 78.5±37.9nM),而 AA 基因型的携带者(均 p<0.05)。SNP rs3742879 与非反应性 PE 患者的精氨酸酶 2 水平降低和一氧化氮形成增加相关。

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