染色体6p21.3区域与脉络膜新生血管及息肉状脉络膜血管病变的相关性分析
发布时间：2018-07-20 19:33
【摘要】：研究背景:老年黄斑变性(age-related macular degeneration,AMD)是老龄化群体中最主要的致盲因素之一,其可以分为萎缩型老年黄斑变性和渗出型老年黄斑变性(wet AMD,wAMD)。wAMD又可以进一步分成典型的脉络膜新生血管(choroidal neovascularization,CNV)和息肉状脉络膜血管病变(polypoidal choroidal vasculopathy,PCV)。CNV和PCV在临床表型上具有较高的相似性,使得有时很难区分这两种疾病。因此,使用遗传学方法找出可用于区分这两种疾病的分子标记能为临床诊断提供指导性的意义。研究目的:对比染色体6p21.3区域内五个基因上的六个单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点 rs541862(CFB),rs429608(SKIV2L),rs12153855(TNXB),rs9391734(FKBPL),rs2071277(NOTCH4)rs3132946(NOTCH4)与中国汉族人群CNV及PCV的相关性,探索CNV与PCV遗传机制的差异。研究方法:本实验收集中国汉族人群CNV病例490例,PCV病例419例,及正常对照者1316例,收集其外周血标本,提取基因组DNA,针对六个SNP位点采用单碱基延伸法进行基因分型。使用病例-对照相关性分析的方法分别研究这六个SNP位点与CNV及PCV的相关性,并进行对比。研究结果:实验表明,TNXB rs12153855,FKBPL rs9391734 及 SKIV2Lrs429608三个SNP位点与CNV的相关性具有统计学意义(P0.05)。其中rs12153855(P = 2.8×10-4,OR=1.8)与rs9391734(P=0.001,OR=1.76)为增加CNV易感性的危险因素,而rs429608(P=2.2×10-4,OR = 0.49)为降低CNV易感性的保护因素。此外,单倍体型分析结果表明,由6p21.3区域上的六个SNP位点组成的AGCAGG和AATGAG单倍体型也与CNV存在相关性(P0.05)。然而,实验结果显示6p21.3区域上的单核苷酸多态性位点及单倍体型与PCV不存在具有统计学意义的相关性(P0.05)。结论:本实验表明染色体6p21.3区域上的rs12153855,rs9391734及rs429608与CNV相关而与PCV无相关性,为这两种疾病的差异提供了遗传学的证据。6p21.3上的这三个单核苷酸多态性位点有为临床检验上区分CNV和PCV的分子标记提供一定的指导意义。
[Abstract]:Background: age-related macular degeneration is one of the leading causes of blindness in an aging population. It can be divided into atrophic senile macular degeneration (wet) and exudative senile macular degeneration (wet). WAMD can be further divided into typical choroidal neovascularization (choroidal) and polypoid choroidal angiopathy (polypoidal choroidal). It is sometimes difficult to distinguish the two diseases. Therefore, the use of genetic methods to identify molecular markers that can be used to distinguish these two diseases can provide guidance for clinical diagnosis. Objective: to investigate the relationship between rs541862 rs429608 (SKIV2L) rs12153855 (TNXBPL) rs9391734 (FKBPL) rs2071277 (NOTCH4) rs3132946 (NOTCH4) in Chinese Han population. Methods: in this experiment, 419 cases of CNV in Chinese Han nationality and 1316 normal controls were collected. The genomic DNA was extracted from peripheral blood samples. The genotyping was carried out by single base extension method for six SNP loci. The correlation of the six SNP sites with CNV and PCV was studied by case-control correlation analysis. Results: the results showed that there were significant correlations between rs9391734 and SKIV2Lrs429608 of TNXBXRs12153855 FKBPL rs9391734 and SKIV2Lrs429608 (P0.05). Rs12153855 (P = 2.8 脳 10 ~ (-4) and rs9391734 (P = 0.001) were the risk factors to increase the susceptibility, and rs429608 (P _ (2.2 脳 10 ~ (-4) OR = 0.49) was the protective factor to decrease the susceptibility. In addition, haploid analysis showed that AGCAGG and AATGAG haplotypes, which were composed of six SNPs in the 6p21.3 region, were also correlated with 6p21.3 (P0.05). However, the results showed that there was no statistically significant correlation between the single nucleotide polymorphisms and haplotypes in the 6p21.3 region (P0.05). Conclusion: the results suggest that rs12153855 rs9391734 and rs429608 are related to 6p21.3, but not to rs429608. These three SNP loci on 6p21.3 provide genetic evidence for the differences between the two diseases and provide some guidance for the molecular markers that distinguish CNV from PCV in clinical tests.
【学位授予单位】：西南交通大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R774.5
本文编号：2134542
[Abstract]:Background: age-related macular degeneration is one of the leading causes of blindness in an aging population. It can be divided into atrophic senile macular degeneration (wet) and exudative senile macular degeneration (wet). WAMD can be further divided into typical choroidal neovascularization (choroidal) and polypoid choroidal angiopathy (polypoidal choroidal). It is sometimes difficult to distinguish the two diseases. Therefore, the use of genetic methods to identify molecular markers that can be used to distinguish these two diseases can provide guidance for clinical diagnosis. Objective: to investigate the relationship between rs541862 rs429608 (SKIV2L) rs12153855 (TNXBPL) rs9391734 (FKBPL) rs2071277 (NOTCH4) rs3132946 (NOTCH4) in Chinese Han population. Methods: in this experiment, 419 cases of CNV in Chinese Han nationality and 1316 normal controls were collected. The genomic DNA was extracted from peripheral blood samples. The genotyping was carried out by single base extension method for six SNP loci. The correlation of the six SNP sites with CNV and PCV was studied by case-control correlation analysis. Results: the results showed that there were significant correlations between rs9391734 and SKIV2Lrs429608 of TNXBXRs12153855 FKBPL rs9391734 and SKIV2Lrs429608 (P0.05). Rs12153855 (P = 2.8 脳 10 ~ (-4) and rs9391734 (P = 0.001) were the risk factors to increase the susceptibility, and rs429608 (P _ (2.2 脳 10 ~ (-4) OR = 0.49) was the protective factor to decrease the susceptibility. In addition, haploid analysis showed that AGCAGG and AATGAG haplotypes, which were composed of six SNPs in the 6p21.3 region, were also correlated with 6p21.3 (P0.05). However, the results showed that there was no statistically significant correlation between the single nucleotide polymorphisms and haplotypes in the 6p21.3 region (P0.05). Conclusion: the results suggest that rs12153855 rs9391734 and rs429608 are related to 6p21.3, but not to rs429608. These three SNP loci on 6p21.3 provide genetic evidence for the differences between the two diseases and provide some guidance for the molecular markers that distinguish CNV from PCV in clinical tests.
【学位授予单位】：西南交通大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R774.5
【参考文献】
相关期刊论文 前1条
1 周家蓬;裴智勇;陈禹保;陈润生;;基于高通量测序的全基因组关联研究策略[J];遗传;2014年11期
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