兰州大学机构库 >学院待认领
类风湿关节炎和冠心病易感SNP分子诊断技术建立及应用
Alternative TitleThe Application and Development of Molecular Diagnosis Technology on SNPs Associated with Rheumatoid Arthritis and Coronary Heart Disease
齐晓明
Thesis Advisor尤崇革
2015-05-21
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Keyword类风湿性关节炎 冠心病 单核苷酸多态性 高分辨率熔解曲线
Abstract目的:自主建立RTKN2、LDLR、APOB、APOC1、ARL15、HLA-DMA、NFKB2、CRP、ACE、NOS3、ENPP1和IQSEC1基因15个SNP位点的分子诊断方法,并探讨15个SNP与兰州地区汉族人群类风湿关节炎(RA)和冠心病(CHD)易感及血清学指标的相关性。方法:基于高分辨熔解技术(HRM)建立上述15个SNP的PCR-HRM检测方法,检测588例RA患者与200例对照和260例CHD患者与238例对照,并测序验证其正确性和适用性。通过病例对照分析筛选RA和CHD 的易感SNP,分析其与RF和抗CCP抗体的相关性。 结果 全部标本PCR-HRM后均能基因分型,经测序验证其正确率达100%。(1)RA病例对照分析显示: rs3125734和rs688基因型及等位基因频率、rs255758和rs1063478基因型频率在两组间有统计学差异。性别分层后rs3125734统计学差异仅见男性,rs688和rs255758仅见女性;血清学分层后统计学有相差异仅见rs3125734和 rs4420638;病例组血脂水平分析显示:rs693和rs4420638与HDL-C间存在统计学差异。(2)CHD病例对照分析显示:rs4353和 rs12528076等位基因频率、rs7830基因型频率在两组间有统计学差异;病例组血脂水平分析显示:rs1205与HDL-C和LDL-C水平关性。 结论 自主建立的PCR-HRM分子诊断方法能够对15个SNP正确基因分型。RTKN2、LDLR、APOC1、ARL15和HLA-DMA与兰州地区汉族人群RA易感相关,其中rs693和rs4420638联合HDL-C血清水平可预警RA发生;ACE、NOS3和ENPP1与兰州地区汉族人群CHD易感相关,其中rs1205联合HDL-C血清水平可预警CHD发生。
Other AbstractObjective:To develop in-house the molecular diagnosis methods of 15 single nucleotide polymorphisms (SNPs) from RTKN2、LDLR、APOB、APOC1、ARL15、HLA-DMA、NFKB2、CRP、ACE、NOS3、ENPP1 and IQSEC1 genes in clinical laboratory, and to explore the relationship of 15 SNPs with the susceptibility of rheumatoid arthritis (RA) and coronary heart disease (CHD) as well as serological indicator in Chinese Han population of Lanzhou area.Methods High resolution melting (HRM) technology was used to establish PCR-HRM assays for detecting fifteen SNPs above-mentioned. Two case-control studies were conducted in 588 RA patients with 200 healthy matched controls and 260 CHD patients with 238 healthy matched controls. The accuracy and clinical applicability of the established assays were verified by directly sequencing on PCR products. Through the case-control analyses, we will screen the SNP loci associated with RA and CHD susceptibility and know the correlation of serum RF and anti-CCP antibodies with the SNPs in Lanzhou Chinese Han population. Result All samples were successfully genotyped using HRM analysis after PCR amplification and the correct rate of assays are found up to 100% by direct sequencing verification.(1)The case-control analysis of RA patients with control subjects showed rs3125734 and rs688 genotype and allele frequencies, rs255758 and rs1063478 genotype frequencies were significantly different between RA and control groups. The result of gender stratification showed that rs3125734 genotype and allele frequencies were significantly different only between male RA patients and control groups; rs688 and rs255758 genotype and allele frequencies were significantly different only between female RA patients and control groups. The results of serological index stratification showed that rs3125734 and rs4420638 allele frequencies were significantly different in CCP positive or RF positive or RF negative RA patients with control groups. The analysis of serum lipid levels showed that the rs693 and rs4420638 SNPs are correlated to RA patients with HDL-C levels.(2)CHD case-control analysis showed rs4353 and rs12528076 allele frequencies, rs7830 genotype frequencies were significantly different between CHD and control groups. The analysis of serum lipid levels showed that the CHD patient group’s rs1205 SNP is correlated to CHD patients with HDL-C and LDL-C levels Conclusion:The established PCR-HRM molecular diagnosis methods on 15 SNPs can correctly genotyped ...
URL查看原文
Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/223080
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
齐晓明. 类风湿关节炎和冠心病易感SNP分子诊断技术建立及应用[D]. 兰州. 兰州大学,2015.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Altmetrics Score
Google Scholar
Similar articles in Google Scholar
[齐晓明]'s Articles
Baidu academic
Similar articles in Baidu academic
[齐晓明]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[齐晓明]'s Articles
Terms of Use
No data!
Social Bookmark/Share
No comment.
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.