發(fā)布時(shí)間：2018-11-04 08:50

【摘要】：目的探討湖南漢族人群散發(fā)性阿爾茨海默病(SAD)與三磷酸腺苷結(jié)合盒轉(zhuǎn)運(yùn)子A1(ATP-binding cassette transporter A1, ABCAl)基因多態(tài)性的關(guān)系。 方法本文采用病例-對(duì)照關(guān)聯(lián)研究,于2010年6月至2010年12月間隨機(jī)收集散發(fā)性AD患者104例及同期非AD認(rèn)知功能正常者104例為對(duì)照組人群。應(yīng)用聚合酶鏈反應(yīng)-限制性片段長度多態(tài)性方法(RFLP-PCR)測定ABCA1R1587K基因多態(tài)性。采用SPSS17.0進(jìn)行統(tǒng)計(jì)分析。 結(jié)果1.與對(duì)照組比較,AD組TC水平顯著高于對(duì)照組(P0.05),HDL-C顯著低于對(duì)照組(P0.05),而兩組間TG和LDL-C水平無顯著差異(P0.05)。 2.單因素Logistic回歸分析顯示,高齡患者的AD發(fā)病風(fēng)險(xiǎn)是低齡患者的2.68倍；有高脂血癥病史患者患AD的風(fēng)險(xiǎn)是無高脂血癥病史患者的2.24倍；高TC患者患AD病風(fēng)險(xiǎn)是低TC患者的2.10倍,低HDL-C患者的AD患病風(fēng)險(xiǎn)是高HDL-C的3.36倍。 3.R1587K等位基因和基因型頻率均符合Hardy-Weinberg平衡吻合度檢測(P0.05)；兩組間基因型及等位基因頻率分布有顯著差異(P0.05), RR、RK和KK基因型頻率在AD組和對(duì)照組分別為58.65%、32.69%、8.66%和46.15%、44.23%、9.62%；R、K基因頻率分別為75.00%、25.00%和68.26%、31.73%。按性別分層后,與對(duì)照組相比,AD組女性患者R1587K三種基因型(RR、RK、KK)分布和等位基因(R、K)頻率比較存在差異,具有統(tǒng)計(jì)學(xué)意義(χ2=5.158,P0.05；χ2=5.357,P0.05)。在男性中R1587K位點(diǎn)基因和基因型頻率與對(duì)照組男性比較也有差異,但未達(dá)到顯著水平(P0.05)。 4.以KK基因型為基礎(chǔ),暴露RR基因型者AD發(fā)病的危險(xiǎn)性增加1.68倍,RK基因型危險(xiǎn)性增加1.30倍。R等位基因攜帶者AD發(fā)病風(fēng)險(xiǎn)是K等位基因的1.62倍。 5.疾病關(guān)聯(lián)度分析顯示R1587K R等位基因可增加AD的發(fā)病風(fēng)險(xiǎn)(OR=2.615,95%CI：0.853-5.156,P=0.039)；進(jìn)一步通過對(duì)性別、年齡、體重指數(shù)、吸煙史、飲酒史和各血脂參數(shù)的有無進(jìn)行校正后,R1587K與AD仍然存在關(guān)聯(lián)性(OR值=2.364,95%CI：0.837-5.421,P=0.041)。 6.AD組中,與KK基因型相比,RR+RK基因型的TC、LDL-C水平顯著增高,而HDL-C顯著降低(P0.05)；與對(duì)照組相比,RR+RK型攜帶者TC、LDL-C顯著增高(P0.05),而HDL-C則顯著降低(P0.05)。 結(jié)論1.湖南漢族人群中散發(fā)性阿爾茨海默病患者的總膽固醇(TC)水平增高,高密度脂蛋白膽固醇(HDL-C)水平降低。 2. ABCA1R1587K基因多態(tài)性與散發(fā)性AD易感性可能存在一定的關(guān)聯(lián)性,RR型及R等位基因可能增加AD的發(fā)病風(fēng)險(xiǎn)。 3.1587K等位基因可能產(chǎn)生有益的臨床血脂譜。
[Abstract]:Objective to investigate the association between (SAD) and ATP-binding cassette transporter A1 (ABCAl) gene polymorphism in Hunan Han population. Methods from June 2010 to December 2010, 104 cases of sporadic AD and 104 cases of non-normal cognitive function of AD were randomly collected from a case-control study as a control group. Polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) was used to detect the polymorphism of ABCA1R1587K gene. SPSS17.0 was used for statistical analysis. Result 1. Compared with the control group, the TC level of AD group was significantly higher than that of the control group (P0.05), HDL-C was significantly lower than that of the control group (P0.05), but there was no significant difference in TG and LDL-C levels between the two groups (P0.05). 2. Univariate Logistic regression analysis showed that the risk of AD in elderly patients was 2.68 times higher than that in young patients, and that in patients with history of hyperlipidemia was 2.24 times higher than that in patients with no history of hyperlipidemia. The risk of AD disease in patients with high TC was 2.10 times higher than that in patients with low TC, and the risk of AD in patients with low HDL-C was 3.36 times higher than that in patients with high HDL-C. 3.R1587K alleles and genotype frequencies were consistent with Hardy-Weinberg equilibrium coincidence (P0.05). The frequencies of genotype and allele of RR,RK and KK in AD group and control group were 58.65% and 46.15% respectively (P 0.05). The RK gene frequencies were 75.00% and 68.26%, respectively. Compared with the control group, the distribution of R1587K genotypes (RR,RK,KK) and the frequency of allele (RNK) in female patients with AD were significantly different from those in the control group (蠂 2, 5.158, P 0.05). 蠂 2 + 5.357 (P0.05). The frequency of R1587K locus gene and genotype in male was also different from that in control group, but it did not reach significant level (P0.05). 4. On the basis of KK genotype, the risk of AD and RK genotype increased by 1.68 times and 1.30 times, respectively. The risk of AD in R allele carriers was 1.62 times higher than that in K allele. 5. Disease correlation analysis showed that R1587K R allele could increase the risk of AD (OR=2.615,95%CI:0.853-5.156,P=0.039). After sex, age, body mass index, smoking history, alcohol consumption history and blood lipid parameters were adjusted, R1587K was still correlated with AD (OR = 2.364 鹵95 CI: 0.837-5.421). In the 6.AD group, the TC,LDL-C level of the, RR RK genotype was significantly higher than that of the KK genotype, while the HDL-C level was significantly decreased (P0.05). Compared with the control group, TC,LDL-C of, RR RK carriers increased significantly (P0.05), while HDL-C decreased significantly (P0.05). Conclusion 1. The total cholesterol (TC) level increased and the high density lipoprotein cholesterol (HDL-C) level decreased in the sporadic Alzheimer's disease patients in Hunan Han population. 2. The polymorphism of ABCA1R1587K gene may be associated with sporadic AD susceptibility. RR type and R allele may increase the risk of AD. The 3.1587K allele may produce beneficial clinical blood lipid profile.
【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】：2012
【分類號(hào)】：R749.16

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本文編號(hào)：2309329