摘要
目的探讨高分辨率熔解曲线(hight-resolution melting,HRM)技术在亚甲基四氢叶酸还原酶(MTHFR)基因分型的应用及rs1801133位点多态性与银川市体检人群高血压的关联性。方法选择2017年1-10月间宁夏医科大学总医院体检人群中高血压患者743例和血压正常者718例为研究对象,收集临床资料,检测血浆同型半胱氨酸(Hcy)、血脂、空腹血糖(FBG)、尿酸等临床生物化学指标。采用HRM技术对样本进行基因分型。结果采用HRM技术成功分型rs1801133位点样本1461例,CC型367例(25.1%)、CT型743例(50.9%)和TT型351例(24.0%),测序验证准确率达100%。银川市人群MTHFR基因rs1801133位点基因型频率和等位基因频率与天津、山东、江苏及湖北人群差异均有统计学意义(P均<0.01)。rs1801133位点CC、CT和TT基因型间血压和Hcy水平差异有统计学意义(P<0.01)。高血压组rs1801133的CC、CT、TT三种基因型频率和C、T等位基因频率与正常组比较差异有统计学意义(P<0.01)。高血压组体质量指数(BMI)、FBG、尿酸、Hcy、甘油三酯(TG)及总胆固醇(TC)均高于正常组(P均<0.01)。Logistic回归分析显示,在校正了年龄、BMI、尿酸及Hcy后rs1801133不同基因型与高血压具有相关性(P<0.01)。结论 HRM法是一种检测准确性高、速度快、低成本的方法,适用于MTHFR基因检测。rs1801133基因多态性与高血压发病显著相关,且直接影响血浆Hcy水平。
Objective To explore the application of high-resolution curve(HRM)in methylenetetr-ahydrofolate reductase(MTHFR) genotyping and the association between rs1801133 polymorphism and hypertension in Yinchuan physical examination population. Methods A total of 743 hypertensive patients and 718 controls were collected from physical examination population between January 2017 and October 2017 at General Hospital of Ningxia Medical University. The clinical data were collected and the clinical biochemical indexes such as plasma homocysteine(Hcy),blood lipid,fasting blood glucose(FBG)and uric acid were measured.HRM was used to genotyping the samples. Results HRM technique was used to successfully classify rs1801133 loci in 1461 cases,CC 367(25.1%),CT 743(50.9%)and TT 351(24.0%)with 100% accuracy. The genotype frequency and allele frequency of MTHFR gene rs1801133 in Yinchuan were significantly different from those in Tianjin,Shandong,Jiangsu and Hubei(P〈0.01). There was a significant difference in blood pressure and Hcy levels among rs1801133 locus CC,CT and TT genotypes(P〈0.01). The frequencies of CC,CT and TT genotypes and C,T alleles of rs1801133 in hypertension group were significantly different from those in normal group(P〈0.01). Body mass index(BMI),FBG,uric acid,Hcy,triglyceride(TG)and total cholesterol(TC)in hypertension group were higher than those in normal group(P〈0.01). Logistic regression analysis showed that different genotypes of rs1801133 were associated with hypertension after adjusting for age,BMI,uric acid and Hcy. Conclusion HRM is a method with high accuracy,high speed and low cost,and is suitable for MTHFR gene detection. Rs1801133 gene polymorphism is significantly related to the incidence of hypertension,and directly affects plasma Hcy level.
作者
田进海
何亚琴
于晶晶
马荣
周瑜
王嘉
王立斌
TIAN Jinhai;HE Yaqin;YU Jingjing;MA Rong;ZHOU Yu;WANG Jia;WANG Libin(Biochip Engineering Center,the General Hospital of Ningxia Medical University,Yinchuan 750004;Stem Cell Institute,the General Hospital of Ningxia Medical University,Yinchuan 750004;Surgery Research Laboratory,the General Hospital of Ningxia Medical University,Yinchuan 750004)
出处
《宁夏医科大学学报》
2018年第8期875-880,共6页
Journal of Ningxia Medical University
基金
国家自然科学基金(81460152)
宁夏医科大学科学研究基金(XZ2016012)
宁夏高等学校一流学科建设项目(NXYLXK2017A05)