miRNA前体-320b-2启动子区单核苷酸多态性与冠心病相关性及对血浆microRNA-320b表达水平的影响  

Analysis on the association of single nucleotide polymorphism in the promoter region of pre-miR- 320b-2 with coronary heart disease risk and factors influencing circulating microRNA-320b level

作　　者：冯晶[1] 黄素丽[2] 何美安[1] 戴霞云[1] 李珺[1] 邓棋霏[1] 邱高坤[1] 杨彬珧[1] 邬堂春[1] 

机构地区：[1]华中科技大学同济医学院公共卫生学院劳动卫生学与环境卫生学系环境与健康教育部重点实验室,武汉430030 [2]深圳市疾病预防控制中心分子生物医学检验科

出　　处：《中华预防医学杂志》2014年第10期893-899,共7页Chinese Journal of Preventive Medicine

基　　金：国家自然科学基金（81230069）

摘　　要：目的探讨中国汉族人群miRNA前体-320b-2（pre-miR-320b-2）启动子区单核苷酸多态性（rs10916581）对冠心病易感性的关联性及对血浆microRNA-320b（miR-320b）表达水平的影响，并探索可能影响血浆miR-320b表达水平的因素。方法采用病例一对照研究方法，于2004年5月至2009年10月应用单纯抽样法随机法选择人住武汉同济医院、协和医院和武钢总医院3个医院冠心病患者1507例和与之年龄、性别频率匹配的1379名健康对照为研究对象，对研究对象的rs10916581位点进行基因分型。从上述人群中采用单纯随机法选择无急性感染疾病的174例冠心病患者，并选择匹配的无急性感染疾病无糖尿病的181名健康对照，应用RT—PCR法检测其血浆miR-320b表达水平。采用多元非条件logistic回归分析rs10916581与冠心病易感性的关联，采用广义线性回归分析各因素与血浆miR-320b表达水平的关联。结果在单因素logistic回归模型中，rs10916581与冠心病易感性的关联性无统计学意义（P值均〉0．05）。在校正年龄、性别、BMI、吸烟状态、糖尿病、高血压、TC／HDL—C比值、总TG后，rs10916581与冠心病易感性的关联性仍无统计学意义[与CC基因型相比，CT、TT、CT＋TT基因型患冠心病的OR（95％CI）值分别为0．94（0．76～1．15）、0．99（0．74～1．33）和0．95（0．78—1．16）]。年龄、性别、吸烟状态、BMI、高血压、糖尿病、冠心病家族史和rs10916581在冠心病的发生中无交互作用（P交互值均〉0．05）。在对照、病例和总人群中，rs10916581均不影响血浆miR-320b的表达水平[B（95％CI）值分别为：-0．028（-0．495～0．440）、0．250（-0．226—0．727）、0．134（-0．218—0．486），P值均〉0．05]。但在病例组中，血浆miR-320b表达水平与BMI负相关[B（95％CI）值为-0．140（-0．261--0．020），P=0．022]，与TC／HDL-C值正相关[8（95％CI）值为0Objective To investigate the effects of rs10916581, a common single nucleotide polymorphism （SNP） located in the promoter region of pre-miR-320b-2, on coronary heart disease （CHD） risk and circulating microRNA-320b （miR-320b） level. To explore potential factors influencing circulating miR-320b level. Methods Rs10916581 was genotyped in a case-control study with 1 507 CHD cases and 1 379 age- and sex-frequency-matched controls. The cases were consecutively recruited from 3 hospitals （Tongji Hospital, Union Hospital, and Wugang Hospital） in Wuhan city （Hubei, China） between May 2004 and October 2009 and all the controls resided in Wuhan communities. A subgroup of 174 CHD cases and 181 non-diabetes controls without acute infection were randomly selected and their circulating miR-320b levels were detected using quantitative reverse transcriptase polymerase chain reaction assays. The association of rs10916581 with CHD susceptibility was analyzed with multivariable logistic regression model. Generalized linear regression model was used to explore the associations of rs10916581 and some other factors with circulating miR-320b level. Results In single-factor logistic regression analysis, no association was found between rs10916581 and CHD risk. After adjustment for age, sex, BMI, smoking status, hypertension, diabetes, total triglyceride, total cholesterol/high density lipoprotein （TC/HDL-C）, the result did not materially alter（compared with CC genotype, the OR（95% CI） of CHR in the subjects carded CT, TT, CT ＋ TT genotypes were 0. 94 （ 0. 76-1.15 ）, 0. 99 （ 0. 74-1.33 ） and 0. 95 （0. 78-1.16 ） ）. No significant interactions were observed between the conventional risk factors of CHD （age, gender, smoking status, BMI, hypertension, diabetes, CHD family history） and rs10916581 on CHD risk （P 〉0.05）. Rs10916581 showed no significant association with circulating miR-320b level in cases, controls or total population （13（95%CI） was -0.028 （-0.495-0.440）, 0.250 �

关 键 词：多态性 单核苷酸 横断面研究 microRNA-320b 冠心病 

分 类 号：R541.4[医药卫生—心血管疾病]