原发性痛风患者外周血单个核细胞DNA甲基转移酶表达的研究

Expression of DNA methyltransferase mRNA in the peripheral blood mononuclear cells of patients with primary gout

目的了解原发性痛风患者DNA甲基转移酶1（DNMT1）、DNA甲基转移酶3A（DNMT3A）、DNA甲基转移酶3B（DNMT3B）的表达水平及作用。方法采用实时荧光定量PCR方法检测50例急性期痛风患者（AG组）、47例间隙期痛风患者（IG组）、44名健康对照组PBMCs中DNMTI、DNMT3A、DNMT3BmRNA的表达水平；采用SPSS19．0统计软件进行分析，计量资料组间比较采用Wilcoxon秩和检验、单因素方差分析，变量间的相关关系采用Spearman相关分析。结果DNMT1在AG组、IG组的PBMCs中表达为[0．0008（0．0004，0．0051）]，[0．0011（0．0004，0．0084）]，较健康对照组表达[0．0017（0．0010，0．0083）]显著降低，差异有统计学意义（F=3．696，P均〈0．05）、DNMT1在AG组和IG组中的mRNA的表达差异无统计学意义（P〉0．05）。DNMT3A在AG组、IG组的PBMCs中的表达为[0．0058（0．0015，0．0179）、0．0128（0．0032，0．0435）]，较健康对照组表达[0．0151（0．0076，0．0727）]降低，差异有统计学意义（F=10．145，P均〈0．05），DNMT3A在AG组的表达较IG组的表达显著降低，差异有统计学意义（P〈0．05）。DNMT3B在AG组、IG组、健康对照组之间表达差异无统计学意义（F=1．826，t9〉0．05）。DNMT1在痛风患者PBMCS中的表达与血肌酐呈正相关（r=0．394，P〈0．05），DNMT3A在痛风患者PBMCs中的表达与红细胞体积（MCV）呈正相关（r=0．588，P〈0．05）。结论原发性痛风患者DNMT1、DNMT3A、DNMT3B基因mRNA的异常表达，提示可能参与了原发性痛风的发生发展、遗传及炎症调节。

Objective To study the expression level and determine the role of DNA methyltransferase 1（DNMT1）, DNA methyltransferase 3A （DNMT3A） and DNA methyhransferase3B （DNMT3B） mRNA in patients with primary gout. Methods DNMT1, DNMT3A, DNMT3B gene mRNA were measured using reverse transcription-polymerase chain reaction （RT-PCR） in the peripheral blood monocytes （PBMCs）. The expression of DNMT1, DNMT3A, DNMT3B gene mRNA in PBMCs were compared among patients with acute gout （AG, n=50）, intermediate gout （IG, n=47） and healthy controls （n=44）. All features were analyzed by Statistical Package forme Soci-Science （SPSS） 19.0 statistical software, Wilcoxon rank sum test, One-Way analysis of variance was used for statistical analysis. Results The expression of DNMT1 mRNA in the group of AG, IG [0.000 8 （0.000 4,0.005 1）], [0.001 1 （0.000 4, 0.008 4）] was significantly lower than that in the healthy controls group [0.001 7 （0.001 0, 0.008 3）, F=3.696, P〈0.05], The expression difference of DNMT1 mRNA between the group of AG and IG was not statistically significant （P〉0.05）, The Expression of DNMT3A mRNA in the group of AG, IG [0.005 8 （0.001 5, 0.017 9）, 0.012 8（0.003 2, 0.043 5）] were significantly lower than that in the healthy controls group [0.015 1 （0.007 6, 0.072 7）, F=10.145, P〈0.05], The expression difference of DNMT3A mRNA between the group of AG and IG was statistically significant （P〈0.05）. The expression of DNMT]B mRNA in the group of AG, IG and healthy controlsgroup were not statistically significant （F=1.86, P〉0.05）. The expression level of DNMT1 was correlated with Crea （r=0.394, P〈0.05）, The expression level of DNMT3A was correlated with MCV （r=0.588, P〈0.05）. Conclusion The abnormal expression of the DNMT1, DNMT3A and DNMT3B mRNA in primary gout patients suggest that they are involved in the pathogenesis of gouty genetic and inflammatory responses.