广西仫佬族人群MRASrs6782181多态性与血脂及高脂血症的关系研究

发布时间：2018-03-01 10:39

  本文关键词： MRAS基因 基因多态性 rs6782181 仫佬族 高胆固醇血症 高甘油三酯血症　出处：《广西医科大学》2015年硕士论文　论文类型：学位论文

【摘要】：研究背景及目的：MRAS rs6782181单核苷酸多态性与血脂谱和动脉粥样硬化性心血管疾病(atherosclerotic cardiovascular disease, ASCVD)的关系在中国人群中研究很少。我国仫佬族人群是一个相对孤立的少数民族,和汉族有着不同的遗传背景。本研究第一目的是探索MRAS rs6782181单核苷酸多态性(single nucleotide polymorphism, SNP)与血浆血脂水平的关系,第二目的是探索MRAS rs6782181 SNP与高脂血症的关系。研究方法：在仫佬族聚集地广西罗城县,采用随机分层抽样方法抽取629名仫佬族人群作为研究对象,同时在当地以同样的方法抽取632名汉族人群作为对照组。按国际心血管流行病学调查方法制定表格,采集人口学特征、社会经济状况、生活方式、饮食习惯和体力活动等资料,询问既往史、家族史等一般情况,体检项目包括身高、体重、体重指数、血压、腰围等。抽取静脉血检测血浆总胆固醇(total cholesterol, TC)、甘油三酯(triglyceride, TG)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol, HDL-C)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol, LDL-C)、载脂蛋白AI (apolipoprotein AI, ApoAI)和载脂蛋白B (apolipoprotein B, ApoB)水平。采用传统的苯酚-氯仿法提取全基因组DNA,采用改良的聚合酶链式反应-限制性片段长度多态性(polymerase chain reaction, restriction fragment length polymorphism, PCR-RFLP)和琼脂糖凝胶电泳方法检测MRAS rs6782181 SNP基因型。研究结果：仫佬族人群身高、饮酒人群百分比、血浆ApoB水平明显高于汉族人群(P0.05-0.01),仫佬族人群体重指数(body mass index,BMI)和舒张压显著低于汉族人群(P0.01),而两民族人群的体重、腰围、吸烟、收缩压、脉压、血糖、TC、TG、HDL-C、LDL-C、ApoAI和ApoAI/ApoB比值比较差异无统计学意义(P0.05)。仫佬族人群AA、 AG和GG基因型频率分别为55.0%、37.4%和7.6%,汉族人群AA、AG和GG基因型频率分别为56.8%、35.9%和7.3%；仫佬族人群A和G的等位基因频率分别为73.7%和26.3%,汉族人群A和G的等位基因频率分别为74.8%和25.2%。两组人群的基因型和等位基因频率的比较差异均没有统计学意义(P0.05)。将仫佬族和汉族人群按照性别分亚组分析,两民族男女之间基因型和等位基因频率亦无统计学差异(P0.05)。仫佬族人群中G等位基因携带者(AG/GG基因型)较非G等位基因携带者(AA基因型)有更高的血浆TC和LDL-C水平(P0.05-0.01)；汉族人群中G等位基因携带者(AG/GG基因型)较非G等位基因携带者(AA基因型)有更高的血浆TC、LDL-C、ApoB水平和更低的ApoAI/ApoB水平(P0.01)。以性别为因素进行亚组分析,仫佬族人群中女性G等位基因携带者(AG/GG基因型)较非G等位基因携带者(AA基因型)有更高的血浆TC水平(P0.05),而在仫佬族男性中无显著差异(P0.05)；汉族人群中男性G等位基因携带者(AG/GG基因型)较非G等位基因携带者(AA基因型)有更高的血浆TC、LDL-C、ApoAI、ApoB水平(P0.05-0.01),汉族女性G等位基因携带者(AG/GG基因型)较非G等位基因携带者有更低的ApoAI水平和ApoAI/ApoB比值(P0.05-0.01)。两民族人群血脂参数还与年龄、性别、吸烟、饮酒、BMI、血糖、腰围和血压等环境因素有关。运用协方差分析统计rs6782181与环境交互作用对血脂的影响,显示rs6782181与吸烟和饮酒的交互作用对血脂的影响。根据吸烟与不吸烟进一步分层,协方差分析(ANCOVA)显示,在吸烟组,G等位基因携带者(AG/GG基因型)较非G等位基因携带者(AA基因型)有更高的血浆TC和LDL-C水平(P0.05-0.01),而在不吸烟组中无此发现。根据饮酒与不饮酒进一步分层,协方差分析显示,在不饮酒组G等位基因携带者(AG/GG基因型)较非G等位基因携带者(AA基因型)有更高的血浆TC水平；在饮酒组G等位基因携带者(AG/GG基因型)较非G等位基因携带者(AA基因型)有更高的ApoB水平和更低的血浆ApoAI/ApoB比值。根据体重指数进一步分层,在BMI≥24 Kg/m2组G等位基因携带者(AG/GG基因型)较非G等位基因携带者(AA基因型)有更高的LDL-C水平和更低的ApoAI/ApoB比值。研究MRASrs6782181与高脂血症之间关系时候发现,高脂血症组人群体重、BMI、腰围、收缩压、舒张压、TC、TG、HDL-C、LDL-C、ApoAI、ApoB和ApoAI/ApoB比值明显高于正常血脂组人群(P0.05-0.001)。正常血脂组A等位基因和G等位基因频率为75.81%和24.19%,AA、AG和GG基因频率分别为58.15%、35.34%和6.52%；高脂血症组A等位基因和G等位基因频率为73.92%和26.08%,AA、AG和GG基因频率分别为56.46%、34.92%和8.62%。基因型与等位基因频率在高脂血症和正常血脂两组间比较差异无统计学意义(P0.05)。logistic回归分析,校正了年龄、性别、BMI、腰围、收缩压、舒张压、吸烟、饮酒统计量后,在显性(AG+GG vs.AA)、隐性(GG vs.AA+AG)、共显性(AG vs.AA+GG)、等位模式(G vs. A)遗传模型下,均没有发现rs6782181对高脂血症的影响,亦没有发现rs6782181对高甘油三酯血症和高胆固醇血症影响。协方差分析显示,在正常组人群中,G等位基因携带者(AG/GG基因型)较非G等位基因携带者(AA基因型)有更低的血浆TC水平,当以性别为亚组分析时,G等位基因携带者(AG/GG基因型)较非G等位基因携带者(AA基因型)在正常血脂组男性中有更低的血浆LDL-C水平,在正常血脂组女性中有更低的血浆TC水平。在高脂血症人群中,血浆TC、TG、HDL-C、LDL-C、ApoAI、 ApoB和ApoAI/ApoB比值在rs6782181三种基因型之间没有差异,当以性别分亚组分析时,亦没有发现有差别。当以性别分亚组分析时,亦无发现有明显差别。当把高脂血症进一步划分为高胆固醇血症和高甘油三酯血症时候,高甘油三酯血症组男性人群中G等位基因携带者(AG/GG基因型)较非G等位基因携带者(AA基因型)有更高的血浆LDL-C水平,在高甘油三酯血症组女性人群中G等位基因携带者(AG/GG基因型)较非G等位基因携带者(AA基因型)有更高的血浆LDL-C和ApoB水平,而在高胆固醇血症组人群中无此发现。结论：1、广西仫佬族人群MRAS rs6782181的基因型和等位基因频率分布以及两个民族之间等位基因和基因型频率比较差异无统计学意义。2、广西仫佬族人群MRAS rs6782181 SNP与血浆TC和LDL-C水平有关；汉族人群MRAS rs6782181 SNP与血浆TC、LDL-C、ApoB和ApoAI/ApoB水平。仫佬族女性人群MRAS rs6782181 SNP与血浆TC水平有关；汉族男性人群ARAS rs6782181 SNP与血浆TC、LDL-C、ApoAI、ApoB水平有关,汉族女性人群MRAS rs6782181 SNP与血浆ApoAI和ApoAI/ApoB水平有关。这种差异可能与民族和性别差异有关。3、MRAS基因rs6782181 SNP与吸烟交互作用影响血浆TC和LDL-C水平。MRAS基因rs6782181 SNP与饮酒交互作用影响血浆ApoB和ApoAI/ApoB水平。MRAS基因rs6782181 SNP与体重指数交互作用影响血浆LDL-C水平和ApoAI/ApoB比值。4、高脂血症组人群和正常血脂组人群,以及两人群男女之间MRAS rs6782181 SNP基因型和等位基因频率比较差异无统计学意义。5、MRAS rs6782181 SNP不影响高脂血症,亦不影响高甘油三酯血症或高胆固醇血症。6、MRAS rs6782181 SNP与正常血脂组人群血浆TC水平有关,与正常血脂组男性人群血浆LDL-C水平有关,与正常血脂组女性人群血浆TC水平有关,而与高脂血症组人群的差异无统计学意义。6、MRAS rs6782181 SNP与高甘油三酯血症组男性人群血浆LDL-C水平有关,与高甘油三酯血症女性人群血浆LDL-C和ApoB水平有关,而在高胆固醇血症组人群中差异无统计学意义。
[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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