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羟基脲治疗镰状细胞贫血患者:编码代谢药物酶的基因多态性与实验室参数的关系。

Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters.

机构信息

Laboratório de Hematologia, Genética e Biologia Computacional (LHGB), Fiocruz Bahia-Instituto Gonçalo Moniz (IGM), Rua Waldemar Falcão 121, Candeal, 40296-710 Salvador, BA, Brazil.

Laboratório de Pesquisa em Anemia (LPA), Departamento de Análises Clínicas, Faculdade de Farmácia, Universidade Federal da Bahia, Rua Barão do Jeremoabo 147, Ondina, 40170-115 Salvador, BA, Brazil.

出版信息

Dis Markers. 2018 Jan 28;2018:6105691. doi: 10.1155/2018/6105691. eCollection 2018.

Abstract

This study investigated associations between SNPs in genes encoding metabolizing drug enzymes and laboratory parameters in sickle cell anemia patients under hydroxyurea (SCA-HU). We evaluated hematologic and biochemical parameters by electronic methods and SNPs by PCR-RFLP and multiplex PCR in 35 SCA-HU patients and 67 SCA-HU patients. The HbS, total cholesterol, lactate dehydrogenase, aspartate aminotransferase, total bilirubin and fractions levels, and leukocyte, eosinophil, monocyte, and erythroblast counts were reduced in SCA-HU patients ( < 0.05). Moreover, they presented higher HbF, C-reactive protein, and ferritin levels and elevated MCH and MCV values ( < 0.05). Genotype frequencies of variants GA + AA of -463G>A and c1c2 + c2c2 of -1293G>C/-1053C>T were higher in SCA-HU patients ( < 0.05). Independent associations were found between the variant A allele and lower total cholesterol, between c2 allele and low alpha-1 antitrypsin and between the null GSTT1 variant and high indirect and total bilirubin in SCA-HU patients. In SCA-HU patients, independent associations were found between the variant A allele and high uric acid and between c2 allele and high urea. Our results suggest that SNPs -463G>A, -1293G>C/-1053C>T, and can be associated with alterations in lipid, inflammatory, renal, hemolytic, and hepatic profiles. However, further studies are needed to elucidate these associations.

摘要

本研究旨在探讨编码代谢药物酶的基因 SNPs 与羟基脲(SCA-HU)治疗下镰状细胞贫血患者实验室参数之间的关系。我们通过电子方法评估了血液学和生化参数,并通过 PCR-RFLP 和多重 PCR 评估了 35 名 SCA-HU 患者和 67 名 SCA-HU 患者的 SNPs。SCA-HU 患者的 HbS、总胆固醇、乳酸脱氢酶、天冬氨酸转氨酶、总胆红素和各分数、白细胞、嗜酸性粒细胞、单核细胞和红细胞计数降低(<0.05)。此外,他们的 HbF、C 反应蛋白和铁蛋白水平较高,MCH 和 MCV 值升高(<0.05)。-463G>A 的 GA+AA 基因型和-1293G>C/-1053C>T 的 c1c2+c2c2 基因型频率在 SCA-HU 患者中较高(<0.05)。在 SCA-HU 患者中,发现变体 A 等位基因与总胆固醇降低独立相关,c2 等位基因与α-1 抗胰蛋白酶降低独立相关,而 GSTT1 无效变体与间接和总胆红素升高独立相关。在 SCA-HU 患者中,发现变体 A 等位基因与尿酸升高独立相关,c2 等位基因与尿素升高独立相关。我们的结果表明,-463G>A、-1293G>C/-1053C>T 和 可能与脂质、炎症、肾脏、溶血性和肝脏特征的改变有关。然而,需要进一步的研究来阐明这些关联。

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