本文選題：9p21 + 大動(dòng)脈粥樣硬化型腦梗死��； 參考：《中南大學(xué)》2014年碩士論文

【摘要】：目的：探討染色體9p21的全基因組關(guān)聯(lián)研究(Genome-wide association study, GWAS)陽(yáng)性位點(diǎn)rs10757274及染色體9p21的1號(hào)單倍型區(qū)域位點(diǎn)rs7049105、rs647188、rs1333035與湖南長(zhǎng)沙地區(qū)漢族人群大動(dòng)脈粥樣硬化型腦梗死(Large-artery atherosclerosis stroke, LAS)的相關(guān)性；探討rs7049105、rs647188、rs1333035位點(diǎn)在有頭頸部動(dòng)脈粥樣硬化證據(jù)的人群中與LAS的相關(guān)性,為L(zhǎng)AS的診斷與治療靶點(diǎn)提供理論依據(jù)。 方法：采用病例對(duì)照研究方法收集湖南長(zhǎng)沙地區(qū)漢族人群中229例LAS患者為病例組,收集同期門診及體檢中心“健康”人群中233例樣本為對(duì)照組1,其中有動(dòng)脈粥樣硬化證據(jù)的樣本150例(64.38%)納入對(duì)照組2,無(wú)動(dòng)脈粥樣硬化證據(jù)的樣本83例(35.62%)納入對(duì)照組3。利用基質(zhì)輔助激光解析飛行時(shí)間質(zhì)譜(matrix-assisted laser desorption inoization-time of flight mass spectrometry, MALDI-TOF-MS)方法對(duì)樣本進(jìn)行基因分型檢測(cè),統(tǒng)計(jì)分析比較病例組與對(duì)照組間rs10757274位點(diǎn)的多態(tài)性分布,并采用Meta分析的方法結(jié)合本次研究及已發(fā)表的rs10757274位點(diǎn)與LAS相關(guān)性研究進(jìn)行定量分析。接著比較病例組與對(duì)照組間rs7049105、rs647188、rs1333035位點(diǎn)的多態(tài)性分布。.最后對(duì)病例組的相關(guān)危險(xiǎn)因素進(jìn)行Logistic回歸分析。 結(jié)果： 1.病例組與對(duì)照組的一般情況比較,在性別、年齡上無(wú)統(tǒng)計(jì)學(xué)差異,p0.05,而在BMI、高血壓、糖尿病病史這些方面有統(tǒng)計(jì)學(xué)差異,p0.05。 2.病例組及對(duì)照組中染色體9p21位點(diǎn)rs7049105(G/A)、rs1333035(T/C)、rs10757274(A/G)均存在多態(tài)性。rs647188位點(diǎn)只檢測(cè)到等位基因A,故不存在多態(tài)性。 3.病例組與對(duì)照組間rs10757274位點(diǎn)的多態(tài)性分布比較未發(fā)現(xiàn)統(tǒng)計(jì)學(xué)顯著性差異(p0.05),但在PUBMED數(shù)據(jù)庫(kù)中檢索以下關(guān)鍵詞："rs10757274"、"9p21.3"、"ANRIL",篩查到7項(xiàng)結(jié)論不相一致的rs10757274位點(diǎn)與LAS相關(guān)性的病例對(duì)照研究,結(jié)合本次研究最終納入8項(xiàng)研究進(jìn)行Meta分析后,總樣本量達(dá)23372例(病例組：5311例,對(duì)照組：18061例),rs10757274位點(diǎn)在顯性模型(OR=1.23,95%CI=1.08-1.41)、隱性模型(OR=1.28,95%CI=1.01-1.61)、等位基因模型(OR=1.10,95%CI=1.06-1.14)中均與LAS呈現(xiàn)相關(guān)性。 4.病例組與對(duì)照組間rs7049105和rs1333035位點(diǎn)的多態(tài)性分布比較結(jié)果如下：①病例組與對(duì)照組1間、病例組與對(duì)照組3間rs7049105和rs1333035位點(diǎn)的多態(tài)性分布比較未發(fā)現(xiàn)統(tǒng)計(jì)學(xué)顯著性差異(p0.05)。②病例組與對(duì)照組2間rs7049105位點(diǎn)的多態(tài)性分布比較未發(fā)現(xiàn)統(tǒng)計(jì)學(xué)顯著性差異(p0.05),病例組與對(duì)照組2間rs1333035位點(diǎn)的基因型頻率分布比較發(fā)現(xiàn)有統(tǒng)計(jì)學(xué)顯著性差異(p=0.039),其中rs1333035位點(diǎn)在顯性模型(CT+TT/CC)中表現(xiàn)出與LAS相關(guān)的傾向(p=0.144, OR=0.382,95%CI=0.122-1.192),故我們猜測(cè)rs1333035的CC基因型可能在有頭頸部動(dòng)脈粥樣硬化證據(jù)的人群中是LAS的保護(hù)性因素。 5.對(duì)病例組建立多因素Logistic回歸方程分析顯示,經(jīng)校正后納入方程的為高血壓病史、糖尿病病史、BMI。rs1333035多態(tài)性位點(diǎn)未納入回歸方程。 結(jié)論 1.染色體9p21的rs1333035多態(tài)性在湖南長(zhǎng)沙地區(qū)有頭頸部動(dòng)脈粥樣硬化證據(jù)的漢族人群中與LAS相關(guān),rs1333035位點(diǎn)的CC基因型可能在湖南長(zhǎng)沙地區(qū)有頭頸部動(dòng)脈粥樣硬化證據(jù)的漢族人群中是LAS的保護(hù)性因素。 2.染色體9p21的rs10757274、rs7049105多態(tài)性與湖南長(zhǎng)沙地區(qū)漢族人群LAS不相關(guān),在湖南長(zhǎng)沙地區(qū)漢族人群中rs647188不存在多態(tài)性。
[Abstract]:Objective : To investigate the association of rs7049105 , rs647188 , rs1333035 , rs1333035 , rs10757274 and rs1333035 of chromosome 9p21 , with large - artery atherosclerosis cerebral infarction ( LAS ) in the Han population in Changsha , Hunan Province .
To investigate the correlation between rs7049105 , rs647188 and rs1333035 locus in the population with evidence of atherosclerosis in the head and neck , and provide theoretical basis for the diagnosis and treatment of LAS .

Methods : A case - control study was used to collect 233 samples from the Han population in Changsha , Hunan . 233 samples were collected in the control group , and the samples were analyzed by matrix - assisted laser scanning inoization - time of flight mass spectrometry ( MALDI - TOF - MS ) . The polymorphism of rs10757274 was analyzed by matrix - assisted laser scanning inoization - time of flight mass spectrometry ( MALDI - TOF - MS ) . Finally , Logistic regression analysis was performed on the relevant risk factors of the case group .

Results :

1 . There was no statistical difference between the case group and the control group , and there was no statistical difference between the case group and the control group , p < 0.05 , while there was statistical difference in BMI , hypertension and diabetes history , p < 0.05 .

2 . There was polymorphism in rs7049105 ( G / A ) , rs1333035 ( T / C ) , rs10757274 ( A / G ) in both case group and control group . rs647188 locus only detected allele A , so there was no polymorphism .

3 . There was no statistically significant difference between case group and control group rs10757274 . However , in PUBMED database , the following keywords were retrieved : " rs10757274 " , " 9p21 . 3 " , " ANDS " , screening to 7 non - consistent rs10757274 sites and LAS - related case - control study . The rs10757274 site was associated with LAS in the dominant model ( OR = 1.23 , 95 % CI = 1.08 - 1.41 ) , recessive model ( OR = 1.28 , 95 % CI = 1.01 - 1.61 ) , allele model ( OR = 1.10 , 95 % CI = 1.06 - 1.14 ) .

4 . The polymorphism distribution of rs7049105 and rs1333035 loci between case group and control group showed no significant difference ( p = 0.039 ) . There was no significant difference ( p = 0.039 ) between case group and control group 2 rs7049105 locus . Among them , rs1333035 locus showed a significant difference in genotype frequency distribution ( p = 0.144 , OR = 0.382 , 95 % CI = 0.122 - 1.192 ) in dominant model ( CT + TT / CC ) . Therefore , we hypothesized that rs1333035 CC genotype might be a protective factor for LAS in the population with evidence of carotid atherosclerosis .

5 . A multivariate logistic regression equation was established for the case group , and the regression equation was not included in the history of hypertension , history of diabetes , BMI and rs1333035 after correction .

Conclusion

1 . The rs1333035 polymorphism of chromosome 9p21 was associated with LAS in Han population with evidence of carotid atherosclerosis in Changsha , Hunan Province . The CC genotype of rs1333035 locus could be the protective factor of LAS in Han population with evidence of carotid atherosclerosis in Changsha , Hunan Province .

2 . rs10757274 , rs7049105 polymorphism of chromosome 9p21 was not related to LAS in Han population in Changsha , Hunan Province , and no polymorphism was found in rs647188 in Han population in Changsha .
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R743.3

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 趙輝,王威,張清潤(rùn),高揚(yáng),趙洪斌,周s，

本文編號(hào)：2089809