本文關(guān)鍵詞：載脂蛋白ApoC-Ⅲ、ApoE基因多態(tài)性與廣西巴馬長壽的相關(guān)性研究　出處：《廣西醫(yī)科大學(xué)》2012年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 載脂蛋白ApoC-Ⅲ 載脂蛋白ApoE 單核苷酸基因多態(tài)性(SNP) 等位基因 交互作用 巴馬 長壽

【摘要】：目的 了解載脂蛋白家族中載脂蛋白C-Ⅲ(Apolipoprotein C-Ⅲ, ApoC-Ⅲ),載脂蛋白E(Apolipoprotein E, ApoE)這兩個候選基因在巴馬研究人群中的分布,探討其基因多態(tài)性與巴馬長壽的相關(guān)性及與生活習(xí)慣(吸煙、飲酒)交互作用對巴馬長壽性狀的影響。 方法 以廣西巴馬地區(qū)為研究地點(diǎn),選取廣西巴馬縣平洞、西山、甲篆三個相連的石山區(qū)鄉(xiāng)鎮(zhèn)為巴馬縣長壽區(qū),其百歲老人比例在巴馬地區(qū)排名前三位(分別為105/10萬、80/10萬、76/10萬)。與之一江之隔的那社、局桑兩個土山區(qū)鄉(xiāng)鎮(zhèn)為巴馬縣非長壽區(qū),其百歲老人比例在巴馬地區(qū)排名最后兩位(分別為21/10萬、15/10萬)。以自然環(huán)境與生活習(xí)慣同巴馬地區(qū)相近的南丹縣小場、里湖兩個鄉(xiāng)鎮(zhèn)為外對照區(qū)。外對照組百歲老人比例低于巴馬縣百歲老人比例(30/10萬,第五次人口普查)�，F(xiàn)場調(diào)查采樣隨機(jī)抽取長壽區(qū)長壽老人152例(年齡90歲以上)為長壽組；長壽區(qū)無長壽家族史的健康成年人342例(年齡22～89歲)為對照1組；非長壽區(qū)無長壽家族史的健康成年人308例(年齡22～89歲)為對照2組；外對照區(qū)無長壽家族史的健康成年人240例(年齡22～89歲)為對照3組；將長壽組與對照1組、2組合并為巴馬組。其中,長壽組與巴馬組為實(shí)驗(yàn)組。提取研究人群外周血基因組DNA,以TaqMan探針實(shí)時熒光定量PCR技術(shù)進(jìn)行基因分型,檢測ApoC-Ⅲ (rs2542052)、ApoE (rs7412/429358)單核苷酸多態(tài)性(Single Nucleotide Polymorphisms,SNPs)。采用卡方檢驗(yàn)及l(fā)ogistic回歸分析等方法進(jìn)行統(tǒng)計(jì)學(xué)處理。 結(jié)果 1.經(jīng)檢驗(yàn),各組人群rs2542052/7412/429358位點(diǎn)基因多態(tài)性符合Hardy-Weinberg遺傳平衡規(guī)律,表明本研究所選樣本具有群體代表性,基因型頻率能代表整個群體水平。 2.本研究結(jié)果顯示,長壽組與對照1、對照3及巴馬組與對照3,ApoC-Ⅲ基因SNP位點(diǎn)rs2542052基因型分布差異具有統(tǒng)計(jì)學(xué)上的意義(P0.05)；巴馬組與對照3,ApoE基因SNP位點(diǎn)rs429358基因型分布差異具有統(tǒng)計(jì)學(xué)上的意義(P0.05)。 3.實(shí)驗(yàn)組與各對照組基因多態(tài)性與巴馬長壽的關(guān)系分析結(jié)果顯示：長壽組與對照1,rs2542052位點(diǎn)多態(tài)性與巴馬長壽無統(tǒng)計(jì)學(xué)關(guān)聯(lián)；長壽組與對照2,rs2542052位點(diǎn)基因型AA、攜帶將等位基因A基因型合并(AC+AA)可能是巴馬長壽性狀的危險因素(OR=2.553,95%CI:1.325-4.921; OR=1.976,95%CI:1.135-3.44);長壽組與對照3,rs2542052位點(diǎn)基因型AC、AA、攜帶將等位基因A基因型合并(AC+AA)可能是巴馬長壽性狀的危險因素(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);巴馬組與對照3,rs2542052位點(diǎn)基因型AA、攜帶將等位基因A基因型合并(AC+AA)可能是巴馬長壽性狀的危險因素(OR=2.,001,95％CI:1.271-3.149；OR=1.531,95%CI：1.009-2.323)：rs7412/429358位點(diǎn)多態(tài)性與巴馬長壽無統(tǒng)計(jì)學(xué)關(guān)聯(lián)。 4.實(shí)驗(yàn)組與各對照組各位點(diǎn)大小等位基因分布比較分析結(jié)果顯示,長壽組與對照2、3及巴馬組與對照3,rs2542052位點(diǎn)的大小等位基因分布差異有統(tǒng)計(jì)學(xué)上的意義(P0.05)rs7412/429358位點(diǎn)的大小等位基因分布差異無統(tǒng)計(jì)學(xué)上的意義(P0.05)。 5.交互作用結(jié)果發(fā)現(xiàn),長壽組與對照1,rs2542052位點(diǎn)與吸煙(P0.05)存在交互作用,攜帶將等位基因A基因型合并(AC+AA)同時有吸煙史的個體抑制巴馬長壽性狀,具有統(tǒng)計(jì)學(xué)上的意義(OR=3.742,95％CI:1.719.8.143). 長壽組與對照2,rs2542052與吸煙(P0.05)、飲酒(P0.05)均存在交互作用： (1)與攜帶基因型CC且無吸煙史個體比較,攜帶將等位基因A基因型合并(AC+AA)且有或無吸煙史的個體可能抑制巴馬長壽性狀(OR=3.107,95％CI:1.587.6.08, OR=9.127,95％CI:3.805-21.894); (2)攜帶基因型CC且無飲酒史個體比較,攜帶將等位基因A基因型合并(AC+AA)且無飲酒史的個體和攜帶基因型CC、將等位基因A基因型合并(AC+AA)同時有飲酒史的個體可能抑制巴馬長壽性狀(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)。 長壽組與對照3,rs2542052與吸煙(P0.05)、飲酒(P0.05)均存在交互作用： (1)與攜帶基因型CC且無吸煙史的個體比較,攜帶將等位基因A基因型合并(AC+AA)同時有吸煙史的個體抑制巴馬長壽性狀,具有統(tǒng)計(jì)學(xué)上的意義(OR=2.269,95%CI:1.252-4.113); (2)與攜帶基因型CC且無飲酒史的個體比較,攜帶將等位基因A基因型合并(AC+AA)且無飲酒史的個體和攜帶基因型CC、將等位基因A基因型合并(AC+AA)同時有飲酒史的個體可能抑制巴馬長壽性狀(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與飲酒(P0.05)存在交互作用。與攜帶基因型TT且無飲酒史的個體比較,攜帶突變基因型TT、將等位基因C基因型合并(CT+CC)同時有飲酒史的個體可能抑制巴馬長壽性狀(OR=4.777,95%CI:2.428-9.398, OR=2.152,95%CI:1.04-4.452)。 巴馬組與對照3,rs2542052與飲酒(P0.05)存在交互作用。攜帶基因型CC且無飲酒史的個體比較,與攜帶攜帶將等位基因A基因型合并(AC+AA)同時有飲酒史的個體可能抑制巴馬長壽性狀(OR=2.936,95%CI:1.57-5.49) rs429358與飲酒(P0.05)存在交互作用。與攜帶基因型TT且無飲酒史的個體比較,攜帶突變基因型TT、將等位基因C基因型合并(CT+CC)同時有飲酒史的個體可能抑制巴馬長壽性狀(OR=1.742,95%CI:1.185-2.561, OR=2.526,95%CI:1.518-4.203)。 6.最小等位基因頻率在相同種族不同民族之間的研究發(fā)現(xiàn),rs2542052/7412差異無統(tǒng)計(jì)學(xué)上的意義(P0.05),rs429358差異具有統(tǒng)計(jì)學(xué)上的意義(P0.05)。 結(jié)論 1.ApoC-Ⅲ基因SNP位點(diǎn)rs2542052基因多態(tài)性與巴馬長壽可能存在關(guān)聯(lián)；ApoE基因SNP位點(diǎn)rs429358基因多態(tài)性與巴馬長壽的相關(guān)性有待進(jìn)一步研究；ApoE基因SNP位點(diǎn)rs7412基因多態(tài)性與巴馬長壽不存在關(guān)聯(lián)。 2.ApoC-Ⅲ基因SNP位點(diǎn)rs2542052與生活習(xí)慣(吸煙、飲酒)可能存在交互作用,并可能與巴馬長壽性狀有關(guān)；ApoE基因SNP位點(diǎn)rs7412與生活習(xí)慣(飲酒)不存在交互作用,與生活習(xí)慣(吸煙)有無交互作用還需進(jìn)一步研究：ApoE基因SNP位點(diǎn)rs429358與生活習(xí)慣(飲酒)可能存在交互作用,并可能與巴馬長壽性狀有關(guān),與生活習(xí)慣(吸煙)無交互作用。
[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.

【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R394

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