载脂蛋白ApoC-Ⅲ、ApoE基因多态性与广西巴马长寿的相关性研究

发布时间：2018-01-12 19:09

本文关键词：载脂蛋白ApoC-Ⅲ、ApoE基因多态性与广西巴马长寿的相关性研究　出处：《广西医科大学》2012年硕士论文　论文类型：学位论文

【摘要】：目的了解载脂蛋白家族中载脂蛋白C-Ⅲ(Apolipoprotein C-Ⅲ, ApoC-Ⅲ),载脂蛋白E(Apolipoprotein E, ApoE)这两个候选基因在巴马研究人群中的分布,探讨其基因多态性与巴马长寿的相关性及与生活习惯(吸烟、饮酒)交互作用对巴马长寿性状的影响。方法以广西巴马地区为研究地点,选取广西巴马县平洞、西山、甲篆三个相连的石山区乡镇为巴马县长寿区,其百岁老人比例在巴马地区排名前三位(分别为105/10万、80/10万、76/10万)。与之一江之隔的那社、局桑两个土山区乡镇为巴马县非长寿区,其百岁老人比例在巴马地区排名最后两位(分别为21/10万、15/10万)。以自然环境与生活习惯同巴马地区相近的南丹县小场、里湖两个乡镇为外对照区。外对照组百岁老人比例低于巴马县百岁老人比例(30/10万,第五次人口普查)。现场调查采样随机抽取长寿区长寿老人152例(年龄90岁以上)为长寿组；长寿区无长寿家族史的健康成年人342例(年龄22～89岁)为对照1组；非长寿区无长寿家族史的健康成年人308例(年龄22～89岁)为对照2组；外对照区无长寿家族史的健康成年人240例(年龄22～89岁)为对照3组；将长寿组与对照1组、2组合并为巴马组。其中,长寿组与巴马组为实验组。提取研究人群外周血基因组DNA,以TaqMan探针实时荧光定量PCR技术进行基因分型,检测ApoC-Ⅲ (rs2542052)、ApoE (rs7412/429358)单核苷酸多态性(Single Nucleotide Polymorphisms,SNPs)。采用卡方检验及logistic回归分析等方法进行统计学处理。结果 1.经检验,各组人群rs2542052/7412/429358位点基因多态性符合Hardy-Weinberg遗传平衡规律,表明本研究所选样本具有群体代表性,基因型频率能代表整个群体水平。 2.本研究结果显示,长寿组与对照1、对照3及巴马组与对照3,ApoC-Ⅲ基因SNP位点rs2542052基因型分布差异具有统计学上的意义(P0.05)；巴马组与对照3,ApoE基因SNP位点rs429358基因型分布差异具有统计学上的意义(P0.05)。 3.实验组与各对照组基因多态性与巴马长寿的关系分析结果显示：长寿组与对照1,rs2542052位点多态性与巴马长寿无统计学关联；长寿组与对照2,rs2542052位点基因型AA、携带将等位基因A基因型合并(AC+AA)可能是巴马长寿性状的危险因素(OR=2.553,95%CI:1.325-4.921; OR=1.976,95%CI:1.135-3.44);长寿组与对照3,rs2542052位点基因型AC、AA、携带将等位基因A基因型合并(AC+AA)可能是巴马长寿性状的危险因素(OR=1.795,95%CI:1.001-3.22; OR=2.389,95%CI:1.28-4.456; OR=2.019,95%CI:1.164-3.502);巴马组与对照3,rs2542052位点基因型AA、携带将等位基因A基因型合并(AC+AA)可能是巴马长寿性状的危险因素(OR=2.,001,95％CI:1.271-3.149；OR=1.531,95%CI：1.009-2.323)：rs7412/429358位点多态性与巴马长寿无统计学关联。 4.实验组与各对照组各位点大小等位基因分布比较分析结果显示,长寿组与对照2、3及巴马组与对照3,rs2542052位点的大小等位基因分布差异有统计学上的意义(P0.05)rs7412/429358位点的大小等位基因分布差异无统计学上的意义(P0.05)。 5.交互作用结果发现,长寿组与对照1,rs2542052位点与吸烟(P0.05)存在交互作用,携带将等位基因A基因型合并(AC+AA)同时有吸烟史的个体抑制巴马长寿性状,具有统计学上的意义(OR=3.742,95％CI:1.719.8.143). 长寿组与对照2,rs2542052与吸烟(P0.05)、饮酒(P0.05)均存在交互作用： (1)与携带基因型CC且无吸烟史个体比较,携带将等位基因A基因型合并(AC+AA)且有或无吸烟史的个体可能抑制巴马长寿性状(OR=3.107,95％CI:1.587.6.08, OR=9.127,95％CI:3.805-21.894); (2)携带基因型CC且无饮酒史个体比较,携带将等位基因A基因型合并(AC+AA)且无饮酒史的个体和携带基因型CC、将等位基因A基因型合并(AC+AA)同时有饮酒史的个体可能抑制巴马长寿性状(OR＝2.448,95％CI:1.248-4.799,OR=4.291,95％CI:1.324-13.909,OR:5.071,95％CI:2.353-10.927)。长寿组与对照3,rs2542052与吸烟(P0.05)、饮酒(P0.05)均存在交互作用： (1)与携带基因型CC且无吸烟史的个体比较,携带将等位基因A基因型合并(AC+AA)同时有吸烟史的个体抑制巴马长寿性状,具有统计学上的意义(OR=2.269,95%CI:1.252-4.113); (2)与携带基因型CC且无饮酒史的个体比较,携带将等位基因A基因型合并(AC+AA)且无饮酒史的个体和携带基因型CC、将等位基因A基因型合并(AC+AA)同时有饮酒史的个体可能抑制巴马长寿性状(OR=2.634,95%CI:1.339-5.179, OR=6.736,95%CI:2.035-22.297, OR=7.037,95%CI:3.108-15.931)。 rs429358与饮酒(P0.05)存在交互作用。与携带基因型TT且无饮酒史的个体比较,携带突变基因型TT、将等位基因C基因型合并(CT+CC)同时有饮酒史的个体可能抑制巴马长寿性状(OR=4.777,95%CI:2.428-9.398, OR=2.152,95%CI:1.04-4.452)。巴马组与对照3,rs2542052与饮酒(P0.05)存在交互作用。携带基因型CC且无饮酒史的个体比较,与携带携带将等位基因A基因型合并(AC+AA)同时有饮酒史的个体可能抑制巴马长寿性状(OR=2.936,95%CI:1.57-5.49) rs429358与饮酒(P0.05)存在交互作用。与携带基因型TT且无饮酒史的个体比较,携带突变基因型TT、将等位基因C基因型合并(CT+CC)同时有饮酒史的个体可能抑制巴马长寿性状(OR=1.742,95%CI:1.185-2.561, OR=2.526,95%CI:1.518-4.203)。 6.最小等位基因频率在相同种族不同民族之间的研究发现,rs2542052/7412差异无统计学上的意义(P0.05),rs429358差异具有统计学上的意义(P0.05)。结论 1.ApoC-Ⅲ基因SNP位点rs2542052基因多态性与巴马长寿可能存在关联；ApoE基因SNP位点rs429358基因多态性与巴马长寿的相关性有待进一步研究；ApoE基因SNP位点rs7412基因多态性与巴马长寿不存在关联。 2.ApoC-Ⅲ基因SNP位点rs2542052与生活习惯(吸烟、饮酒)可能存在交互作用,并可能与巴马长寿性状有关；ApoE基因SNP位点rs7412与生活习惯(饮酒)不存在交互作用,与生活习惯(吸烟)有无交互作用还需进一步研究：ApoE基因SNP位点rs429358与生活习惯(饮酒)可能存在交互作用,并可能与巴马长寿性状有关,与生活习惯(吸烟)无交互作用。
[Abstract]:objective
To understand the apolipoprotein family in apolipoprotein C- (Apolipoprotein C- ApoC- III, III), apolipoprotein E (Apolipoprotein E ApoE) distribution of the two candidate genes in the study population, to explore the relationship between gene polymorphism and longevity and life habits (smoking, drinking) interaction the role of Bama longevity traits.
Method
In Guangxi Bama area as the research site, select the Guangxi Bama County adit, Xishan Township, Jiazhuan three connected area for Bama District, the proportion of centenarians in Bama area ranked in the top three (respectively 105/10 million, 80/10 million, 76/10 million). The agency of the river. Bureau of township two mulberry soil mountain area for non longevity area of Bama County, the proportion of centenarians in Bama area ranked last two (respectively 21/10 million, 15/10 million). Nandan County small field in natural environment and living habits with Bama area are similar to that in the two townships of Lake District as. The control group is lower than the proportion of centenarians in Bama centenarians proportion (30/10 million, Fifth Census). Field investigation sampling randomly from Changshou District longevity in 152 cases (age 90 years) for the longevity Group; no family history of longevity longevity areas in 342 healthy adults (age 22~89 years) for According to the 1 group; no non familial history of longevity longevity areas in 308 healthy adults (aged 22 to 89 years) as control group 2; the external control area without a family history of longevity 240 healthy adults (aged 22 to 89 years) as control group 3; the longevity Group and the control group 1, 2 and combination Bama group. Among them, the longevity Group and the Bama group as experimental group. The genomic DNA of peripheral blood extraction study population, with real-time fluorescence quantitative PCR TaqMan probe genotyping, detection of ApoC- III (rs2542052), ApoE (rs7412/429358) single nucleotide polymorphism (Single Nucleotide Polymorphisms, SNPs). The Chi square test and logistic regression analysis was used for statistical analysis.
Result
1., after testing, the rs2542052/7412/429358 locus polymorphism of each group accords with the Hardy-Weinberg genetic balance rule. It shows that the selected samples have group representation and genotype frequency can represent the whole population level.
2. the results of this study show that the longevity Group and the control group 3 and 1, Bama group and 3 of the control group, with statistically significant difference of SNP gene rs2542052 genotype distribution of ApoC- (P0.05); Bama group and control 3, distribution of SNP gene rs429358 genotype ApoE has statistically significance (P0.05).
3. the experimental group and the control group, gene polymorphism and analysis of the relationship between Bama longevity showed that the longevity Group and control 1, rs2542052 polymorphism was not associated with longevity in Bama longevity Group and control; 2, rs2542052 genotype AA, carrying the allele A and genotype (AC+AA) can be dangerous factors of Bama longevity traits (OR=2.553,95%CI:1.325-4.921; OR=1.976,95%CI:1.135-3.44); longevity Group and control 3, rs2542052 genotype AC, AA, carrying the A allele genotype combination (AC+AA) may be a risk factor for longevity traits (OR=1.795,95%CI:1.001-3.22; OR=2.389,95%CI:1.28-4.456; OR=2.019,95%CI:1.164-3.502); Bama group and control 3, rs2542052 genotype AA that will carry the A allele genotype combination (AC+AA) may be a risk factor for longevity traits (OR=2., 001,95%CI:1.271-3.149; OR=1.531, 95%CI:1.009-2.323) there was no statistically significant association between:rs7412/429358 locus polymorphism and Bama longevity.
4. the experimental group and the control group of each size allele comparison analysis showed that the longevity Group and control group and control 2,3 and Obama 3, there were statistically significant differences in the distribution of allele size of rs2542052 loci (P0.05) had no statistically significant size of allele distribution between rs7412/429358 loci (P0.05).
5. the interaction analysis showed that the longevity Group and 1 of the control group, rs2542052 (P0.05) gene smoking interaction with genotype A allele (AC+AA) with a history of smoking and the inhibition of individual longevity traits, with statistical significance (OR=3.742,95%CI: 1.719.8.143).
There was a interaction between rs2542052 and smoking (P0.05) and drinking (P0.05) in both the longevity Group and the control 2.
(1) compared with individuals with genotype CC and no smoking history, individuals carrying allele A genotype (AC+AA) with or without smoking history may inhibit Bama longevity traits (OR=3.107,95%CI:1.587.6.08, OR=9.127,95%CI:3.805-21.894).
(2) genotype CC and no more drinking history of individuals, will carry the A allele with type (AC+AA) and no history of alcohol and individual genotype CC, the genotype A allele (AC+AA) with a history of alcohol and the individual may inhibit the Bama longevity traits (OR = 2.448,95%CI:1.248-4.799, OR=4.291,95%CI:1.324-13.909, OR:5.071,95%CI:2.353-10.927).
There was a interaction between rs2542052 and smoking (P0.05) and drinking (P0.05) in both the longevity Group and the control 3.
(1) compared with individuals with genotype CC and no smoking history, individuals with allele A genotype (AC+AA) and smoking history had significant statistical significance (OR=2.269,95%CI:1.252-4.113).
(2) and genotype CC with no smoking individual comparison, with genotype A allele (AC+AA) combined with no smoking and individual genotype CC, the genotype A allele (AC+AA) with a history of alcohol and the individual may inhibit the Bama longevity traits (OR=2.634,95%CI:1.339-5.179, OR=6.736,95%CI:2.035-22.297, OR=7.037,95%CI:3.108-15.931).
Rs429358 (P0.05) and alcohol interaction. And genotype TT with no smoking individual, carrying mutations in genotype TT, the genotype C allele (CT+CC) with a history of alcohol and the individual may inhibit the Bama longevity traits (OR=4.777,95%CI:2.428-9.398, OR=2.152,95%CI:1.04-4.452).
Bama group and control group 3, rs2542052 has interaction with drinking (P0.05). Individuals carrying genotype CC and alcohol free history may have longer life history (OR=2.936,95%CI: 1.57-5.49) than those carrying the allele A genotype (AC+AA) with drinking history.
Rs429358 (P0.05) and alcohol interaction. And genotype TT with no smoking individual, carrying mutations in genotype TT, the genotype C allele (CT+CC) with a history of alcohol and the individual may inhibit the Bama longevity traits (OR=1.742,95%CI:1.185-2.561, OR=2.526,95%CI:1.518-4.203).
6., the minimum allele frequency in the same race and different ethnic groups found that rs2542052/7412 difference was not statistically significant (P0.05), rs429358 difference was statistically significant (P0.05).
conclusion
The polymorphism of 1.ApoC- SNP gene rs2542052 locus may be associated with longevity in Bama. The correlation between ApoE gene rs429358 polymorphism and Bama longevity needs further study; ApoE gene SNP locus polymorphism is not associated with longevity in Bama.
2.ApoC- gene SNP locus rs2542052 and living habits (smoking, drinking) interaction may exist, and may be associated with longevity traits; ApoE SNP gene rs7412 and living habits (drinking) there was no interaction, and living habits (smoking) there is no interaction needs further study: ApoE SNP gene rs429358 and living habits (drinking) interaction may exist, and may be associated with longevity related traits, and living habits (smoking) no interaction.

【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R394

【参考文献】