SLC2A9、SLC22A12、ABCG2、P2RX7基因启动子区甲基化与原发性痛风  

Methylation of SLC2A9,SLC22A12,ABCG2,P2RX7 in promoter and primary gout

作　　者：应颖[1] 陈勇[1] 张顺[2] 黄海燕[3] 李晓可[3] 邹荣鑫 褚赞波 黄娴倩[1] 彭勇[1] 干敏芝[1] 耿保庆 朱梦雅[1] 王筱萍[1] YING Ying;CHEN Yong;ZHANG Shun;HUANG Hai-yan;LI Xiao-ke;ZOU Rong-xin;CHU Zan-bo;HUANG Xian-qian;PENG Yong;GAN Min-zhi;GENG Bao-qing;ZHU Meng-ya;WANG Xiao-ping(Department of Rheumatology,Ningbo No.2 Hospital,Ningbo 315010,China;Stem Cell and Regenerative Medicine Laboratory,Ningbo No.2 Hospital,Ningbo 315010,China;Medical School of Ningbo University,Ningbo 310000,China)

机构地区：[1]宁波市第二医院风湿免疫科,浙江宁波315010 [2]宁波市第二医院肝细胞与再生医学实验室,浙江宁波315010 [3]宁波大学医学院,310000

出　　处：《中华临床免疫和变态反应杂志》2018年第5期510-516,共7页Chinese Journal of Allergy & Clinical Immunology

基　　金：浙江省医药卫生基金(2015KYB346;2017KY589)~~

摘　　要：目的探讨基因(SLC2A9、SLC22A12、ABCG2和P2RX7)启动子区甲基化在原发性痛风中的作用。方法于2016年1月至2017年1月在宁波市第二医院纳入原发性痛风患者50例,同期纳入50例健康体检者作为对照,采集所有受检者的外周血,采用焦磷酸测序技术检测SLC2A9、SLC22A12、ABCG2和P2RX7基因的甲基化率。采用SPSS 20. 0统计学软件对痛风组和对照组间的DNA甲基化率进行比较。结果痛风组患者SLC2A9 (pos 1、3、4、5、7)低于对照组、SLC22A12pos 2高于对照组,ABCG2 (pos 1、2、4、5、6)甲基化率明显低于对照组,差异均有统计学意义(P<0. 05)。其中痛风组与对照组SLC2A9基因各位点的甲基化率分别明显不同[pos 1:(0. 56±0. 05)%比(1. 27±0. 12)%,P=0. 042; pos 3:(0. 07±0. 01)%比(0. 82±0. 03)%,P=0. 012; pos 4:(1. 22±0. 23)%比(2. 69±0. 78)%,P=0. 043; pos 5:(0. 01±0. 00)%比(0. 76±0. 13)%,P=0. 003; pos 7:(0. 01±0. 00)%比(0. 87±0. 03)%,P=0. 003];基因SLC22A12 [pos 2:(94. 05±1. 13)%比(93. 15±2. 04)%,P=0. 008];基因ABCG2 [pos 1:(0. 76±0. 12)%比(1. 52±0. 34)%,P=0. 007; pos 2:(0. 12±0. 01)%比(0. 68±0. 11)%,P=0. 033; pos 4:(1. 06±0. 02)%比(1. 82±0. 32)%,P=0. 033;pos 5:(0. 10±0. 01)%比(0. 90±0. 02)%,P=0. 017; pos 6:(0. 04±0. 00)%比(0. 58±0. 03)%,P=0. 004]。但分析该3个基因的功能,只有基因SLC2A9的结果可解释痛风的发病机制。结论 SLC2A9(pos 1、3、4、5、7)低甲基化水平可能增加原发性痛风的风险。Objective To investigate whether promoter DNA methylation of SLC2A9,SLC22A12,ABCG2 and P2RX7 genes contributes to the risk of primary gout.Methods A total of 50 patients diagnosed with primary gout and 50 healthy controls were included in Ningbo No.2 Hospital from January 2016 to January 2017.The methylation levels of SLC2A9,SLC22A12,ABCG2,and P2RX7 genes were detected by pyrophosphate sequencing technology.Statistical analyses was performed using SPSS version 20.0.Results The methylation levels of SLC2A9(pos 1,3,4,5,7),SLC22A12 pos 2 and ABCG2(pos 1,2,4,5,6)were significantly lower in primary gout than those in the healthy controls(P<0.05).The methylation levels of gene SLC2A9 between gout group and control group were significantly different[pos 1:(0.56±0.05)%vs.(1.27±0.12)%,P=0.042;pos 3:(0.07±0.01)%vs.(0.82±0.03)%,P=0.012;pos 4:(1.22±0.23)vs.(2.69±0.78)%,P=0.043;pos 5:(0.01±0.00)%vs.(0.76±0.13)%,P=0.003;pos 7:(0.01±0.00)%vs.(0.87±0.03)%,P=0.003];gene SLC22A12[pos 2:(94.05±1.13)%vs.(93.15±2.04)%,P=0.008];gene ABCG2[pos 1:(0.76±0.12)%vs.(1.52±0.34)%,P=0.007;pos 2:(0.12±0.01)%vs.(0.68±0.11)%,P=0.033;pos 4:(1.06±0.02)%vs.(1.82±0.32)%,P=0.033;pos 5:(0.10±0.01)%vs.(0.90±0.02)%,P=0.017;pos 6:(0.04±0.00)%vs.(0.58±0.03)%,P=0.004].However,after analyzing the function of these three genes,only the results of SLC2A9 can explain the pathogenesis of gout.Conclusion The lower methylation levels of SLC2A9(pos 1,3,4,5,7)might be the risk of primary gout.

关 键 词：基因启动子区 原发性痛风 甲基化 表观遗传 

分 类 号：R589.7[医药卫生—内分泌]