The Large-scale Deletions and Copy Numbers of Mitochondrial DNA in Gout Patients Treated with Allopurinol

Le Lan Phuong, Tran Le Huyen Linh, Le Thi Thanh Nhan, Bui Phuong Thao, Tran Thi Huyen Trang, Nguyen Van Hung, Nguyen Thi Van Anh, Trinh Hong Thai
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Abstract

Allopurinol is now the first-line treatment for managing gout and its increasing usage has brought more gout patients at risk of developing allopurinol-induced hypersensitive reactions. Up to now, our attempts to identify the biomarkers for hypersensitivity to allopurinol are still finite. Besides, the association between drug-induced hypersensitive reactions and some mitochondrial DNA (mtDNA) alterations has been proved but remains unclear in gout patients. In this study, 41 blood samples of gout patients prescribed with allopurinol including 22 hypersensitive and 29 tolerant ones were used to analyze their mtDNA large-scale deletions through PCR and determine the mtDNA deletion level and the copy number by quantitative PCR. The results indicated that the mtDNA large-scale deletions and mtDNA copy number of the hypersensitive group were lower than that of the tolerant one (p < 0.05). However, no association was found between the mtDNA deletion level and the appearance of hypersensitive reactions in gout patients. In addition, the study showed that the mtDNA deletion level and copy number were negatively correlated with the copy numbers of mitochondrial DNA in gout patients (R = -0.3495; p = 0.0119) and allopurinol hypersensitive group (R = -0.6744; p = 0.0005). Thus, a decrease in mtDNA copy number might serve as a potential biomarker for further investigation to assess the risk of hypersensitive reactions to allopurinol in gout patients.  
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别嘌呤醇治疗痛风患者线粒体DNA的大规模缺失和拷贝数
别嘌呤醇现在是治疗痛风的一线药物,其使用的增加使更多的痛风患者面临发生别嘌呤醇诱导的过敏反应的风险。到目前为止,我们对别嘌呤醇过敏的生物标志物的鉴定仍然有限。此外,药物引起的过敏反应与痛风患者的一些线粒体DNA (mtDNA)改变之间的关系已得到证实,但仍不清楚。本研究采用别嘌呤醇治疗的痛风患者41例血样,其中过敏者22例,耐受者29例,通过PCR分析其mtDNA大规模缺失,定量PCR测定其mtDNA缺失水平和拷贝数。结果表明,超敏组mtDNA大规模缺失和mtDNA拷贝数均低于耐受组(p < 0.05)。然而,没有发现mtDNA缺失水平与痛风患者过敏反应的出现之间的关联。此外,研究发现痛风患者mtDNA缺失水平和拷贝数与线粒体DNA拷贝数呈负相关(R = -0.3495;p = 0.0119)和别嘌呤醇过敏组(R = -0.6744;P = 0.0005)。因此,mtDNA拷贝数的减少可能作为一种潜在的生物标志物,用于进一步研究评估痛风患者对别嘌呤醇过敏反应的风险。
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