本文關(guān)鍵詞： MRAS基因 基因多態(tài)性 rs6782181 仫佬族 高膽固醇血癥 高甘油三酯血癥　出處：《廣西醫(yī)科大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：研究背景及目的：MRAS rs6782181單核苷酸多態(tài)性與血脂譜和動脈粥樣硬化性心血管疾病(atherosclerotic cardiovascular disease, ASCVD)的關(guān)系在中國人群中研究很少。我國仫佬族人群是一個相對孤立的少數(shù)民族,和漢族有著不同的遺傳背景。本研究第一目的是探索MRAS rs6782181單核苷酸多態(tài)性(single nucleotide polymorphism, SNP)與血漿血脂水平的關(guān)系,第二目的是探索MRAS rs6782181 SNP與高脂血癥的關(guān)系。研究方法：在仫佬族聚集地廣西羅城縣,采用隨機分層抽樣方法抽取629名仫佬族人群作為研究對象,同時在當(dāng)?shù)匾酝瑯拥姆椒ǔ槿?32名漢族人群作為對照組。按國際心血管流行病學(xué)調(diào)查方法制定表格,采集人口學(xué)特征、社會經(jīng)濟狀況、生活方式、飲食習(xí)慣和體力活動等資料,詢問既往史、家族史等一般情況,體檢項目包括身高、體重、體重指數(shù)、血壓、腰圍等。抽取靜脈血檢測血漿總膽固醇(total cholesterol, TC)、甘油三酯(triglyceride, TG)、高密度脂蛋白膽固醇(high-density lipoprotein cholesterol, HDL-C)、低密度脂蛋白膽固醇(low-density lipoprotein cholesterol, LDL-C)、載脂蛋白AI (apolipoprotein AI, ApoAI)和載脂蛋白B (apolipoprotein B, ApoB)水平。采用傳統(tǒng)的苯酚-氯仿法提取全基因組DNA,采用改良的聚合酶鏈?zhǔn)椒磻?yīng)-限制性片段長度多態(tài)性(polymerase chain reaction, restriction fragment length polymorphism, PCR-RFLP)和瓊脂糖凝膠電泳方法檢測MRAS rs6782181 SNP基因型。研究結(jié)果：仫佬族人群身高、飲酒人群百分比、血漿ApoB水平明顯高于漢族人群(P0.05-0.01),仫佬族人群體重指數(shù)(body mass index,BMI)和舒張壓顯著低于漢族人群(P0.01),而兩民族人群的體重、腰圍、吸煙、收縮壓、脈壓、血糖、TC、TG、HDL-C、LDL-C、ApoAI和ApoAI/ApoB比值比較差異無統(tǒng)計學(xué)意義(P0.05)。仫佬族人群AA、 AG和GG基因型頻率分別為55.0%、37.4%和7.6%,漢族人群AA、AG和GG基因型頻率分別為56.8%、35.9%和7.3%；仫佬族人群A和G的等位基因頻率分別為73.7%和26.3%,漢族人群A和G的等位基因頻率分別為74.8%和25.2%。兩組人群的基因型和等位基因頻率的比較差異均沒有統(tǒng)計學(xué)意義(P0.05)。將仫佬族和漢族人群按照性別分亞組分析,兩民族男女之間基因型和等位基因頻率亦無統(tǒng)計學(xué)差異(P0.05)。仫佬族人群中G等位基因攜帶者(AG/GG基因型)較非G等位基因攜帶者(AA基因型)有更高的血漿TC和LDL-C水平(P0.05-0.01)；漢族人群中G等位基因攜帶者(AG/GG基因型)較非G等位基因攜帶者(AA基因型)有更高的血漿TC、LDL-C、ApoB水平和更低的ApoAI/ApoB水平(P0.01)。以性別為因素進行亞組分析,仫佬族人群中女性G等位基因攜帶者(AG/GG基因型)較非G等位基因攜帶者(AA基因型)有更高的血漿TC水平(P0.05),而在仫佬族男性中無顯著差異(P0.05)；漢族人群中男性G等位基因攜帶者(AG/GG基因型)較非G等位基因攜帶者(AA基因型)有更高的血漿TC、LDL-C、ApoAI、ApoB水平(P0.05-0.01),漢族女性G等位基因攜帶者(AG/GG基因型)較非G等位基因攜帶者有更低的ApoAI水平和ApoAI/ApoB比值(P0.05-0.01)。兩民族人群血脂參數(shù)還與年齡、性別、吸煙、飲酒、BMI、血糖、腰圍和血壓等環(huán)境因素有關(guān)。運用協(xié)方差分析統(tǒng)計rs6782181與環(huán)境交互作用對血脂的影響,顯示rs6782181與吸煙和飲酒的交互作用對血脂的影響。根據(jù)吸煙與不吸煙進一步分層,協(xié)方差分析(ANCOVA)顯示,在吸煙組,G等位基因攜帶者(AG/GG基因型)較非G等位基因攜帶者(AA基因型)有更高的血漿TC和LDL-C水平(P0.05-0.01),而在不吸煙組中無此發(fā)現(xiàn)。根據(jù)飲酒與不飲酒進一步分層,協(xié)方差分析顯示,在不飲酒組G等位基因攜帶者(AG/GG基因型)較非G等位基因攜帶者(AA基因型)有更高的血漿TC水平；在飲酒組G等位基因攜帶者(AG/GG基因型)較非G等位基因攜帶者(AA基因型)有更高的ApoB水平和更低的血漿ApoAI/ApoB比值。根據(jù)體重指數(shù)進一步分層,在BMI≥24 Kg/m2組G等位基因攜帶者(AG/GG基因型)較非G等位基因攜帶者(AA基因型)有更高的LDL-C水平和更低的ApoAI/ApoB比值。研究MRASrs6782181與高脂血癥之間關(guān)系時候發(fā)現(xiàn),高脂血癥組人群體重、BMI、腰圍、收縮壓、舒張壓、TC、TG、HDL-C、LDL-C、ApoAI、ApoB和ApoAI/ApoB比值明顯高于正常血脂組人群(P0.05-0.001)。正常血脂組A等位基因和G等位基因頻率為75.81%和24.19%,AA、AG和GG基因頻率分別為58.15%、35.34%和6.52%；高脂血癥組A等位基因和G等位基因頻率為73.92%和26.08%,AA、AG和GG基因頻率分別為56.46%、34.92%和8.62%�；蛐团c等位基因頻率在高脂血癥和正常血脂兩組間比較差異無統(tǒng)計學(xué)意義(P0.05)。logistic回歸分析,校正了年齡、性別、BMI、腰圍、收縮壓、舒張壓、吸煙、飲酒統(tǒng)計量后,在顯性(AG+GG vs.AA)、隱性(GG vs.AA+AG)、共顯性(AG vs.AA+GG)、等位模式(G vs. A)遺傳模型下,均沒有發(fā)現(xiàn)rs6782181對高脂血癥的影響,亦沒有發(fā)現(xiàn)rs6782181對高甘油三酯血癥和高膽固醇血癥影響。協(xié)方差分析顯示,在正常組人群中,G等位基因攜帶者(AG/GG基因型)較非G等位基因攜帶者(AA基因型)有更低的血漿TC水平,當(dāng)以性別為亞組分析時,G等位基因攜帶者(AG/GG基因型)較非G等位基因攜帶者(AA基因型)在正常血脂組男性中有更低的血漿LDL-C水平,在正常血脂組女性中有更低的血漿TC水平。在高脂血癥人群中,血漿TC、TG、HDL-C、LDL-C、ApoAI、 ApoB和ApoAI/ApoB比值在rs6782181三種基因型之間沒有差異,當(dāng)以性別分亞組分析時,亦沒有發(fā)現(xiàn)有差別。當(dāng)以性別分亞組分析時,亦無發(fā)現(xiàn)有明顯差別。當(dāng)把高脂血癥進一步劃分為高膽固醇血癥和高甘油三酯血癥時候,高甘油三酯血癥組男性人群中G等位基因攜帶者(AG/GG基因型)較非G等位基因攜帶者(AA基因型)有更高的血漿LDL-C水平,在高甘油三酯血癥組女性人群中G等位基因攜帶者(AG/GG基因型)較非G等位基因攜帶者(AA基因型)有更高的血漿LDL-C和ApoB水平,而在高膽固醇血癥組人群中無此發(fā)現(xiàn)。結(jié)論：1、廣西仫佬族人群MRAS rs6782181的基因型和等位基因頻率分布以及兩個民族之間等位基因和基因型頻率比較差異無統(tǒng)計學(xué)意義。2、廣西仫佬族人群MRAS rs6782181 SNP與血漿TC和LDL-C水平有關(guān)；漢族人群MRAS rs6782181 SNP與血漿TC、LDL-C、ApoB和ApoAI/ApoB水平。仫佬族女性人群MRAS rs6782181 SNP與血漿TC水平有關(guān)；漢族男性人群ARAS rs6782181 SNP與血漿TC、LDL-C、ApoAI、ApoB水平有關(guān),漢族女性人群MRAS rs6782181 SNP與血漿ApoAI和ApoAI/ApoB水平有關(guān)。這種差異可能與民族和性別差異有關(guān)。3、MRAS基因rs6782181 SNP與吸煙交互作用影響血漿TC和LDL-C水平。MRAS基因rs6782181 SNP與飲酒交互作用影響血漿ApoB和ApoAI/ApoB水平。MRAS基因rs6782181 SNP與體重指數(shù)交互作用影響血漿LDL-C水平和ApoAI/ApoB比值。4、高脂血癥組人群和正常血脂組人群,以及兩人群男女之間MRAS rs6782181 SNP基因型和等位基因頻率比較差異無統(tǒng)計學(xué)意義。5、MRAS rs6782181 SNP不影響高脂血癥,亦不影響高甘油三酯血癥或高膽固醇血癥。6、MRAS rs6782181 SNP與正常血脂組人群血漿TC水平有關(guān),與正常血脂組男性人群血漿LDL-C水平有關(guān),與正常血脂組女性人群血漿TC水平有關(guān),而與高脂血癥組人群的差異無統(tǒng)計學(xué)意義。6、MRAS rs6782181 SNP與高甘油三酯血癥組男性人群血漿LDL-C水平有關(guān),與高甘油三酯血癥女性人群血漿LDL-C和ApoB水平有關(guān),而在高膽固醇血癥組人群中差異無統(tǒng)計學(xué)意義。
[Abstract]:Background and objective: MRAS rs6782181 single nucleotide polymorphism and dyslipidemia and atherosclerotic cardiovascular disease (atherosclerotic cardiovascular, disease, ASCVD) to study the relationship between China rarely in the crowd. China Mulao population is a relatively isolated ethnic minorities have different genetic background and the Han nationality. The first objective is to explore the MRAS rs6782181 single nucleotide polymorphism (single nucleotide polymorphism, SNP) and plasma lipid levels between the second aim is to explore the relationship of MRAS rs6782181 SNP and hyperlipidemia. Research methods: gathered in Guangxi Luocheng County in Mulao nationality, as the research object by using the random sampling method 629 Mulao people, at the same time to the local the same method to extract 632 Han population as the control group. Making table according to the International Cardiovascular Epidemiology survey method, mining In demographic characteristics, socioeconomic status, lifestyle, dietary habits and physical activity data, medical history, family history and other general physical examination items, including height, weight, body mass index, blood pressure, waist circumference. Venous blood was sampled for detection of plasma total cholesterol (total, cholesterol, TC), triglycerides (triglyceride, TG) and high density lipoprotein cholesterol (high-density lipoprotein, cholesterol, HDL-C), low density lipoprotein cholesterol (low-density lipoprotein, cholesterol, LDL-C), apolipoprotein AI (apolipoprotein AI ApoAI) and apolipoprotein B (apolipoprotein B ApoB). By using traditional phenol chloroform method to extract genomic DNA by polymerase. The modified chain reaction restriction fragment length polymorphism (polymerase chain reaction restriction fragment, length polymorphism, PCR-RFLP) and agarose gel electrophoresis method Detection of MRAS rs6782181 SNP genotypes. Results: the height of Mulam people, drinking population percentage, plasma ApoB levels were significantly higher than Han population (P0.05-0.01), Mulao people (body mass index, BMI BMI) and diastolic blood pressure were significantly lower than the Han population (P0.01), and the two ethnic groups of body weight, waist circumference, smoking. The systolic blood pressure, pulse pressure, blood glucose, TC, TG, HDL-C, LDL-C, ApoAI and ApoAI/ApoB ratio was not statistically significant difference (P0.05). Mulao populations of AA, AG and GG genotype frequencies were 55%, 37.4% and 7.6%, the Han nationality AA, AG and GG genotype frequencies were 56.8% and 35.9%. 7.3%; A and G populations Mulao allele frequencies were 73.7% and 26.3%, A and G in Han population allele frequencies were compared between 74.8% and 25.2%. of two groups of genotype and allele frequencies were not statistically significant (P0.05). The Mulao Nationality According to sex and Han population subgroup analysis, there was no statistical difference between the two national male and female genotype and allele frequency (P0.05). G Mulao population allele (AG/GG genotype) than G allele (AA genotype) had higher plasma levels of LDL-C and TC (P0.05-0.01) G; Han population allele (AG/GG genotype) than G allele (AA genotype) had higher plasma levels of TC, LDL-C, ApoB level and lower ApoAI/ApoB level (P0.01). In the sex factor subgroup analysis of Mulao populations of women G allele (AG/GG genotype) than G allele (AA genotype) had higher plasma TC levels (P0.05), but no significant difference in Mulao nationality male (P0.05); G male Han population allele (AG/GG genotype) with G allele gene carriers (AA Genotype) plasma TC, higher LDL-C, ApoAI, ApoB (P0.05-0.01), Han female carriers of the G allele (AG/GG genotype) than G allele carriers had lower levels of ApoAI and ApoAI/ApoB ratio (P0.05-0.01). The two ethnic groups have lipid parameters with age, gender, smoking. Drinking, BMI, blood glucose, waist circumference and blood pressure and other environmental factors. The use of rs6782181 statistical analysis of covariance effects and environmental interaction on blood lipids, show the effects of rs6782181 and smoking and drinking alcohol interaction on blood lipids. According to smoking and smoking further stratified, covariance analysis (ANCOVA) showed that in the smoking group, G allele (AG/GG genotype) than G allele (AA genotype) had higher plasma levels of LDL-C and TC (P0.05-0.01), and in the non-smoking group not found. According to drinking and drinking further stratified analysis of covariance In the show, not drinking group G allele (AG/GG genotype) than G allele (AA genotype) had higher plasma TC levels in drinking group; G allele (AG/GG genotype) than G allele (AA genotype) plasma ApoAI/ApoB ratio have a higher ApoB level and lower BMI. According to further stratification, BMI = 24 in group Kg/m2 G allele (AG/GG genotype) than G allele (AA genotype) ApoAI/ApoB ratio have higher LDL-C level and lower. The study of the relationship between MRASrs6782181 and hyperlipidemia it was found that the weight, hyperlipidemia group BMI, waist circumference, systolic blood pressure, diastolic blood pressure, TC, TG, HDL-C, LDL-C, ApoAI, ApoB and ApoAI/ApoB were significantly higher than those in normal blood lipid group (P0.05-0.001). Normal blood lipid group A allele and G allele frequencies were 75.81% and 24.19%, AA. AG 鍜孏G鍩哄洜棰戠巼鍒嗗埆涓，

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