【摘要】：研究背景:老年黃斑變性(age-related macular degeneration,AMD)是老齡化群體中最主要的致盲因素之一,其可以分為萎縮型老年黃斑變性和滲出型老年黃斑變性(wet AMD,wAMD)。wAMD又可以進(jìn)一步分成典型的脈絡(luò)膜新生血管(choroidal neovascularization,CNV)和息肉狀脈絡(luò)膜血管病變(polypoidal choroidal vasculopathy,PCV)。CNV和PCV在臨床表型上具有較高的相似性,使得有時(shí)很難區(qū)分這兩種疾病。因此,使用遺傳學(xué)方法找出可用于區(qū)分這兩種疾病的分子標(biāo)記能為臨床診斷提供指導(dǎo)性的意義。研究目的:對(duì)比染色體6p21.3區(qū)域內(nèi)五個(gè)基因上的六個(gè)單核苷酸多態(tài)性(single nucleotide polymorphisms,SNPs)位點(diǎn) rs541862(CFB),rs429608(SKIV2L),rs12153855(TNXB),rs9391734(FKBPL),rs2071277(NOTCH4)rs3132946(NOTCH4)與中國(guó)漢族人群CNV及PCV的相關(guān)性,探索CNV與PCV遺傳機(jī)制的差異。研究方法:本實(shí)驗(yàn)收集中國(guó)漢族人群CNV病例490例,PCV病例419例,及正常對(duì)照者1316例,收集其外周血標(biāo)本,提取基因組DNA,針對(duì)六個(gè)SNP位點(diǎn)采用單堿基延伸法進(jìn)行基因分型。使用病例-對(duì)照相關(guān)性分析的方法分別研究這六個(gè)SNP位點(diǎn)與CNV及PCV的相關(guān)性,并進(jìn)行對(duì)比。研究結(jié)果:實(shí)驗(yàn)表明,TNXB rs12153855,FKBPL rs9391734 及 SKIV2Lrs429608三個(gè)SNP位點(diǎn)與CNV的相關(guān)性具有統(tǒng)計(jì)學(xué)意義(P0.05)。其中rs12153855(P = 2.8×10-4,OR=1.8)與rs9391734(P=0.001,OR=1.76)為增加CNV易感性的危險(xiǎn)因素,而rs429608(P=2.2×10-4,OR = 0.49)為降低CNV易感性的保護(hù)因素。此外,單倍體型分析結(jié)果表明,由6p21.3區(qū)域上的六個(gè)SNP位點(diǎn)組成的AGCAGG和AATGAG單倍體型也與CNV存在相關(guān)性(P0.05)。然而,實(shí)驗(yàn)結(jié)果顯示6p21.3區(qū)域上的單核苷酸多態(tài)性位點(diǎn)及單倍體型與PCV不存在具有統(tǒng)計(jì)學(xué)意義的相關(guān)性(P0.05)。結(jié)論:本實(shí)驗(yàn)表明染色體6p21.3區(qū)域上的rs12153855,rs9391734及rs429608與CNV相關(guān)而與PCV無(wú)相關(guān)性,為這兩種疾病的差異提供了遺傳學(xué)的證據(jù)。6p21.3上的這三個(gè)單核苷酸多態(tài)性位點(diǎn)有為臨床檢驗(yàn)上區(qū)分CNV和PCV的分子標(biāo)記提供一定的指導(dǎo)意義。
[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.
【學(xué)位授予單位】：西南交通大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R774.5

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本文編號(hào)：2134542