ORAI1基因rs3741596单核苷酸多态性与川崎病的研究

发布时间：2018-05-01 08:04

本文选题：ORAI1基因 + 单核苷酸多态性　；参考：《天津医科大学》2017年硕士论文

【摘要】：目的:川崎病(Kawasaki disease,KD)全基因组关联研究显示钙释放激活钙调节蛋白1(Calcium release-activated calcium modulator 1,CRACM1(ORAI1))基因rs3741596位点单核苷酸多态性(single nucleotide polymorphism,SNP)与KD易感性及冠状动脉损害(Coronary artery lesions,CALs)有关。该研究在中国北方汉族人群中尚无报道。本研究以中国北方汉族KD患儿及健康儿童对照组为研究对象,旨在探讨ORAI1基因rs3741596位点基因型频率及等位基因频率与KD易感性及并冠状动脉损害是否相关。方法:采用病例对照研究方法,选取2016年2月至2016年6月于天津市儿童医院住院确诊为KD患儿46例为病例组[1,2],同一时期我院门诊健康体检的儿童25例为对照组,并根据有无CALs将病例组分为CAL组和NCAL组。采集所有研究对象外周静脉血2ml,提取基因组DNA,应用聚合酶链反应(polymerase chain reaction,PCR)技术扩增目的基因片段,联合基因直接测序法检测所有研究对象基因组DNA ORAI1基因rs3741596位点SNP。比较KD组与对照组间、以及CAL组与NCAL组间该位点基因型频率和等位基因频率的分布情况,进行统计学分析。结果:所有研究对象均检测到ORAI1基因rs3741596位点SNP,该位点存在AA、AG及GG三种基因型。1.KD病例组和对照组间ORAI1基因rs3741596位点AA、AG及GG基因型频率分布差异不显著(χ~2=0.712,P=0.701)。而AA基因型频率在病例组及对照组中均明显高于AG及GG。2.KD病例组和对照组间ORAI1基因rs3741596位点等位基因(A和G)频率分布差异不显著(χ~2=0.499,P=0.480)。3.CAL组和NCAL组间ORAI1基因rs3741596位点AA、AG和GG基因型频率分布差异显著(χ~2=6.524,P=0.038);而NCAL组中AA基因型频率明显高于CAL组(OR=0.678)。4.CAL组与NCAL组间ORAI1基因rs3741596位点等位基因频率分布差异显著(χ~2=6.891,P=0.009);CAL组中G等位基因频率高于NCAL组(OR=4.333),NCAL组中A等位基因频率高于CAL组(OR=0.796)。结论:1.ORAI1基因rs3741596位点存在AA、AG和GG三种基因型,该SNP可能与KD易感性无关。2.ORAI1基因rs3741596位点SNP可能与KD并发CALs易感性有关。3.ORAI1基因rs3741596位点AA基因型可能对防止KD并发冠脉损伤发挥作用。4.ORAI1基因rs3741596位点G等位基因可能是KD并发CALs的危险因素,A等位基因可能为防止KD并发CALs的保护因素。
[Abstract]:Objective: a genome-wide association study of Kawasaki disease (Kawasaki disease) showed that the single nucleotide polymorphisms (SNPs) of the rs3741596 locus of the calcium release activated calmodulin (1(Calcium release-activated calcium modulator 1) were associated with the susceptibility to KD and coronary artery lesions (CALs). The study has not been reported in the Han population in northern China. The purpose of this study was to investigate whether the genotype frequency and allele frequency of rs3741596 locus of ORAI1 gene were correlated with susceptibility to KD and coronary artery damage. Methods: from February 2016 to June 2016, 46 children with KD diagnosed in Tianjin Children's Hospital were selected as the case group, and 25 children in the same period were selected as the control group. The patients were divided into CAL group and NCAL group according to the presence or absence of CALs. The genomic DNA was extracted from peripheral venous blood of all the subjects. The target gene fragment was amplified by polymerase chain reaction- PCR technique, and the rs3741596 locus of genomic DNA ORAI1 gene was detected by direct gene sequencing. To compare the distribution of genotype frequency and allele frequency between KD group and control group, as well as between CAL group and NCAL group. Results: the rs3741596 locus of ORAI1 gene was detected in all subjects. There were three genotypes of AA-AG and GG. 1. There was no significant difference in the frequency distribution of ORAI1 gene rs3741596 locus, AAAG and GG genotypes between the two groups (蠂 ~ (2 +) ~ (0.712) P ~ (1) P ~ (0.701). The frequency of AA genotype was significantly higher in case group and control group than that in AG and GG.2.KD group and control group. There was no significant difference in the frequency distribution of ORAI1 rs3741596 locus allele A and G between CAL group and NCAL group. 3. ORAI1 rs3741596 locus AA-AG and GG gene in CAL group and NCAL group were not significantly different from those in control group. The frequency distribution of ORAI1 gene rs3741596 in NCAL group was significantly higher than that in CAL group and NCAL group (蠂 2 + 6.891). The frequency of G allele in NCAL group was higher than that in NCAL group (P < 0. 009). The frequency of AA genotype in NCAL group was significantly higher than that in CAL group. 4. The allele frequency of ORAI1 gene rs3741596 locus in CAL group and NCAL group was higher than that in NCAL group. The frequency of locus gene was higher than that of CAL group. Conclusion: 1. There are three genotypes of AA-AG and GG at the rs3741596 locus of ORAI1 gene. This SNP may be independent of KD susceptibility. 2. ORAI1 gene rs3741596 site SNP may be related to KD complicated with CALs susceptibility. 3. ORAI1 gene rs3741596 locus AA genotype may play a role in preventing KD from complicated coronary artery injury. 4. ORAI1 gene rs3741596 locus G allele may be The risk factor of KD complicated with CALs is the A allele, which may be the protective factor of KD complicated with CALs.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R725.4

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