ABCA1基因外显子R1587K多态性与阿尔茨海默病血脂水平及易感性的关联分析
发布时间：2018-11-04 08:50
【摘要】：目的探讨湖南汉族人群散发性阿尔茨海默病(SAD)与三磷酸腺苷结合盒转运子A1(ATP-binding cassette transporter A1, ABCAl)基因多态性的关系。 方法本文采用病例-对照关联研究,于2010年6月至2010年12月间随机收集散发性AD患者104例及同期非AD认知功能正常者104例为对照组人群。应用聚合酶链反应-限制性片段长度多态性方法(RFLP-PCR)测定ABCA1R1587K基因多态性。采用SPSS17.0进行统计分析。 结果1.与对照组比较,AD组TC水平显著高于对照组(P0.05),HDL-C显著低于对照组(P0.05),而两组间TG和LDL-C水平无显著差异(P0.05)。 2.单因素Logistic回归分析显示,高龄患者的AD发病风险是低龄患者的2.68倍；有高脂血症病史患者患AD的风险是无高脂血症病史患者的2.24倍；高TC患者患AD病风险是低TC患者的2.10倍,低HDL-C患者的AD患病风险是高HDL-C的3.36倍。 3.R1587K等位基因和基因型频率均符合Hardy-Weinberg平衡吻合度检测(P0.05)；两组间基因型及等位基因频率分布有显著差异(P0.05), RR、RK和KK基因型频率在AD组和对照组分别为58.65%、32.69%、8.66%和46.15%、44.23%、9.62%；R、K基因频率分别为75.00%、25.00%和68.26%、31.73%。按性别分层后,与对照组相比,AD组女性患者R1587K三种基因型(RR、RK、KK)分布和等位基因(R、K)频率比较存在差异,具有统计学意义(χ2=5.158,P0.05；χ2=5.357,P0.05)。在男性中R1587K位点基因和基因型频率与对照组男性比较也有差异,但未达到显著水平(P0.05)。 4.以KK基因型为基础,暴露RR基因型者AD发病的危险性增加1.68倍,RK基因型危险性增加1.30倍。R等位基因携带者AD发病风险是K等位基因的1.62倍。 5.疾病关联度分析显示R1587K R等位基因可增加AD的发病风险(OR=2.615,95%CI：0.853-5.156,P=0.039)；进一步通过对性别、年龄、体重指数、吸烟史、饮酒史和各血脂参数的有无进行校正后,R1587K与AD仍然存在关联性(OR值=2.364,95%CI：0.837-5.421,P=0.041)。 6.AD组中,与KK基因型相比,RR+RK基因型的TC、LDL-C水平显著增高,而HDL-C显著降低(P0.05)；与对照组相比,RR+RK型携带者TC、LDL-C显著增高(P0.05),而HDL-C则显著降低(P0.05)。 结论1.湖南汉族人群中散发性阿尔茨海默病患者的总胆固醇(TC)水平增高,高密度脂蛋白胆固醇(HDL-C)水平降低。 2. ABCA1R1587K基因多态性与散发性AD易感性可能存在一定的关联性,RR型及R等位基因可能增加AD的发病风险。 3.1587K等位基因可能产生有益的临床血脂谱。
[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 卤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.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R749.16
[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 卤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.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R749.16
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