BCAR1 PDE1C OPRD1 NRXN1启动子区甲基化水平在痛风和高尿酸血症中的初步研究

Preliminary study on deoxyribonucleic acid methylation of breast cancer anti-resistance 1,phospho-diesterase 1C,opioid receptor delta 1 and neurexin 1 in gout and hyperuricemia

目的初探BCAR1、PDE1C、OPRD1以及NRXN1基因启动子区甲基化水平的改变与原发性痛风及高尿酸血症的相关性。方法在中国科学院大学宁波华美医院门诊及体检中心同期随机选取原发性痛风患者50例、高尿酸血症患者30例和健康对照体检者50名,提取脱氧核糖核酸(DNA),经甲基化转化后对3组受试者BCAR1、PDE1C、NRXN1以及OPRD14个基因启动子区的目标序列进行焦磷酸测序,得到其甲基化率。采用方差分析和非参数检验对3组病例的4种基因启动子区甲基化率进行统计学分析。结果受试者工作特征曲线(ROC曲线)分析提示PDE1C(pos4、pos5、pos6)的甲基化水平对诊断痛风有较高的准确性,ROC曲线下面积(AUC)为0.712、0.772、0.775,P均<0.05;OPRD1 pos4的甲基化水平对诊断高尿酸血症有较高的准确性(AUC=0.733,P<0.05)。结论DNA甲基化可能与痛风及高尿酸血症的发病和炎症反应具有一定的相关性,但仍需进一步研究。

Objective To provide a preliminary theoretical basis for gout and hyperuricemia of Deoxyribonucleic acid (DNA) methylation.Methods Breast cancer anti-resistance 1(BCAR1), phospho-diesterase 1C (PDE1C), opioid receptor delta 1(OPRD1) and neurexin 1(NRXN1) methylation levels were measured by bisulfite pyrosequencing in 50 gout patients, 30 hyperuricemia patients and 50 matched healthy controls. Comparisons between groups were evaluated by F-test and Nonparametric tests.Results Receiver operating characteristic showed that the methylation of PDE1C(pos4, pos5, pos6)(AUC: 0.712, 0.772, 0.775;all P values<0.05) had higher accuracy for diagnosis of gout, and OPRD1 pos4 (AUC=0.733, P<0.05) had higher accuracy for hyperuricemia.Conclusion DNA methylation may play a role in the development of gout and hyperuricemia, however, further studies are needed.