代谢综合征环境因素与APOA1-APOC3-APOA4-APOA5基因簇基因多态性的交互作用研究

发布时间：2018-04-29 20:38

  本文选题：代谢综合征 + 患病率　； 参考：《吉林大学》2015年博士论文

【摘要】：代谢综合征是由机体脂肪、蛋白质及碳水化合物等代谢异常聚集而成的复杂的代谢紊乱症候群,包括中心性肥胖、血脂代谢异常、血压异常升高及血糖异常升高。代谢综合征的发生与遗传因素、生活方式、饮食习惯等密切相关。患有代谢综合征的人群,有更高的风险罹患2型糖尿病、心血管疾病、癌症、痛风、非酒精性脂肪肝、多囊卵巢综合征、睡眠呼吸暂停综合征和痴呆等疾病。目的：了解吉林省成人代谢综合征的患病率及分布特征,分析影响代谢综合征患病的环境危险因素；探讨APOA1-APOC3-APOA4-APOA5基因簇基因多态性与代谢综合征的关联；分析环境危险因素和APOA1-APOC3-APOA4-APOA5基因簇基因的交互作用对代谢综合征发病的影响,为探讨代谢综合征的病因学研究、制定代谢综合征的防治策略提供依据。方法：①代谢综合征的患病率与影响因素分析数据来源于2012年吉林省成人慢性病及其危险因素调查研究。从该调查21435例有效样本中选择可以进行代谢综合征诊断的16831名常住居民作为本研究的研究对象,结合身体测量和实验室检测进行代谢综合征的诊断及环境危险因素的收集。按2010年全国第六次人口普查,吉林省人口分布情况进行加权调整,计算吉林省代谢综合征患病率,应用单因素、多因素logistic回归探讨代谢综合征相关环境危险因素。②APOA1-APOC3-APOA4-APOA5基因簇基因多态性与代谢综合征的关联分析以第一部分研究中随机抽取的1807名代谢综合征患者为病例组,以排除其他代谢系统疾病及恶性肿瘤等严重躯体疾病的匹配健康人作为对照；采用飞行质谱方法检测基因组DNA中APOA1-APOC3-APOA4-APOA5基因簇7个SNPs的多态性,利用基于散发病例-对照研究的关联分析方法探讨APOA1-APOC3-APOA4-APOA5基因簇基因多态性与代谢综合征的关联。③采用多因素Logistic回归模型分析APOA1-APOC3-APOA4-APOA5基因与环境危险因素交互作用对代谢综合征发病的影响。结果：①本研究中可进行代谢综合征相关诊断的有效调查问卷共计16831份,占2012年吉林省成人慢性病及其危险因素调查研究全部完访问卷的78.52%。经复杂加权吉林省成人代谢综合征的患病率为32.86%,其中男性患病率为36.64%,女性患病率为29.66%,男性高于女性(P0.05)。城市患病率为33.86%,农村患病率为31.80%,城市高于农村(P0.05)。②调查对象中,中心性肥胖阳性率50.81%；血压升高阳性率52.18%；甘油三酯水平升高阳性率41.18%；高密度脂蛋白胆固醇降低阳性率31.06%；血糖水平升高阳性率30.22%。③影响代谢综合征患病的危险因素包括高龄(OR=8.621,95%CI=6.594-11.272),从事脑力劳动(OR:1.098,95%CI=1.008.1.195),心脑血管疾病家族史(OR=1.297, 95%CI=1.211-1.389),糖尿病家族史(OR=1.630,95%CI=1.484.1.791),现在吸烟(OR=1.259,95%CI=1.108-1.429),高盐饮食(OR=1.252,95%CI=1.149-1.363),以及饮酒(OR=1.217,95%CI=1.116-1.327)等,保护因素包括女性(OR=0.723, 95%CI=0.663-0.789),水果及乳制品摄入每周超过2次等(P0.001)。④携带APOAlrs5072位点T等位基因的人群较携带C等位基因的人群患代谢综合征的危险性更高(ORT/C=1.617,95%CI=1.478-1.770),超显性遗传模式下,携带TC基因型人群较携带CC+TT基因型人群,患代谢综合征的危险性更高(ORTC/TT+CC=1.617,95%CI=1.478-1.770).APOC3rs5128位点的最优遗传模式为超显性遗传模式,该模式下携带GC基因型的人群患代谢综合征的危险性是携带GG+CC基因型人群的1.238倍(95%CI=1.089-1.407)。rs2854117位点等位基因与基因型与代谢综合征不相关(P0.05).APOA4rs5128位点的最优遗传模式为超显性遗传模式,该模式下携带GA基因型的人群患代谢综合征的危险性是携带GG+AA基因型人群的1.168倍(95%CI=1.025-1.331)。携带APOA5rs662799位点G等位基因的人群较携带A等位基因的人群患代谢综合征的危险性更高(ORG/A=1.450,95%CI=1.312-1.602),共显性遗传模式下,携带GG基因型及携带GA基因型人群较携带AA基因型人群,患代谢综合征的危险性更高(ORGG/AA=1.232,95%CI=1.746-2.852,ORGA/AA=1.392,95%CI=1.217-1.592).携带APOA5rs651821位点C等位基因的人群较携带T等位基因的人群患代谢综合征的危险性更高(ORC/T=1.443,95%CI=1.306-1.594),共显性遗传模式下,携带CC基因型及携带TC基因型人群较携带TT基因型人群,患代谢综合征的危险性更高(ORCC/TT=2.253,95%CI=1.746-2.883, ORTC/TT=1.375,95%CI=1.203-1.572)。携带APOA5rs2075291位点T等位基因的人群较携带G等位基因的人群患代谢综合征的危险性更高(ORT/G=1.424,95%CI=1.170-1.732),显性遗传模式下,携带GT+TT基因型人群较携带GG基因型人群,患代谢综合征的危险性更高(ORGT+TT/GG=2.253,95%CI=1.168-1.760).⑤与甘油三酯异常升高相关的各位点等位基因包括rs5072位点T等位基因,rs5128 C等位基因,rs5104A等位基因,rs662799 G等位基因,rs651821 C等位基因和rs2075291 T等位基因(P0.05)。与甘油三酯异常升高相关的基因型包括：rs5072 TC+TT基因型,rs5128 GC+CC基因型,rs2854117 GA+AA基因型,rs5104 GA+GG基因型,rs662799 AA基因型和GA基因型,rs651821 CC基因型和TC基因型,rs2075291 GT+TT基因型(P0.05)。与高密度脂蛋白胆固醇异常降低相关的等位基因包括rs662799 G等位基因,rs651821 C等位基因,rs2075291 T等位基因(P0.05)。与高密度脂蛋白胆固醇异常降低相关的基因型包括rs5072 TC+TT基因型,rs662799 AA或GA基因型,rs651821 CC或TC基因型(P0.05)。与血压异常升高相关的等位基因包括rs2854117 A等位基因,rs662799 G等位基因,rs651821 C等位基因和rs2075291 T等位基因(P0.05)。与血压异常升高相关的基因型包括rs5128 GC基因型,rs5104GA基因型,rs662799 AA或GA基因型,rs651821 CC或TC基因型,rs2075291 GT+TT基因型(P0.05)。与中心性肥胖相关的等位基因包括rs662799 G等位基因,rs651821 C等位基因和rs2075291 T等位基因(P0.05),与中心性肥胖相关的相关的基因型包括rs5072 TC基因型,rs5128GC基因型,rs662799 AA或GA基因型,rs651821 CC或TC基因型,rs2075291 GT+TT基因型(P0.05)。与血糖异常升高相关的等位基因包括rs662799 G等位基因,rs651821C等位基因和rs2075291 T等位基因(P0.05)。与中心性肥胖相关的相关的基因型包括rs5072 TC基因型,rs5128GC基因型,rs5104 GA基因型,rs662799 AA或GA基因型,rs651821 CC或TC基因型和rs2075291 GT+TT基因型(P0.05)。⑥POA5rs662799位点与吸烟,饮酒状况存在交互作用(PGE0.05),其它位点与环境因素间未见交互作用(PGE0.05)。结论：①吉林省代谢综合征加权调整患病率为32.86%；男性患病率为36.64%,女性患病率为29.66%；城市患病率为33.86%,农村患病率为31.80%。②影响代谢综合征患病的危险因素包括男性,高龄,从事脑力劳动,心脑血管疾病家族史,糖尿病家族史,现在吸烟,高盐饮食,水果及乳制品摄入少以及饮酒等。③APOA1, APOC3, APOA4, APOA5基因可能是代谢综合征的易感基因,APOA1-APOC3-APOA4-APOA5基因簇可能与代谢综合征发病相关联④APOA1, APOC3, APOA4, APOA5基因与代谢综合征各异常因子存在关联,APOA1-APOC3-APOA4-APOA5基因簇可能与代谢综合征各异常因子相关。⑤APOA5rs662799位点与吸烟、饮酒对代谢综合征的发病的影响存在交互作用。
[Abstract]:Metabolic syndrome is a complex metabolic disorder syndrome characterized by abnormal metabolism of body fat , protein and carbohydrate , including central obesity , abnormal blood lipid metabolism , abnormal elevation of blood pressure and abnormal blood sugar . The occurrence of metabolic syndrome is closely related to genetic factors , lifestyle , eating habits and so on . The aim of this study is to understand the prevalence and distribution of metabolic syndrome in Jilin Province .
To investigate the association of APOA1 - APOC3 - APOA4 - APOA5 gene cluster gene polymorphism with metabolic syndrome ;
The effects of environmental risk factors and the interaction of APOA1 - APOC3 - APOA4 - APOA5 gene cluster gene on the pathogenesis of metabolic syndrome were analyzed .
The polymorphism of APOA1 - APOC3 - APOA4 - APOA5 gene cluster in genomic DNA was detected by flight mass spectrometry . The association between APOA1 - APOC3 - APOA4 - APOA5 gene cluster and metabolic syndrome was investigated by using the association analysis method based on sporadic case - control study .
The positive rate of blood pressure was 52.18 % .
The positive rate of triglyceride was 41.18 % .
The positive rate of high density lipoprotein cholesterol was 31.06 % .
There was a higher risk of metabolic syndrome ( OR = 1.259 , 95 % CI = 1.107 , 95 % CI = 1.478 - 1.770 ) . There was a higher risk of metabolic syndrome ( OR = 1.259 , 95 % CI = 1.107 , 95 % CI = 1.478 - 1.770 ) . The genotype including rs5072 TC + TT genotype , rs662799 AA or GA genotype , rs651821 CC or TC genotype , rs651821 CC or TC genotype , rs2075291 GT + TT genotype ( P0.05 ) . The genotype associated with abnormal elevation of triglyceride included rs5072 TC + TT genotype , rs651821 CC or TC genotype , rs2075291 GT + TT genotype ( P0.05 ) . The alleles associated with abnormal elevation of triglyceride include rs5072 TC + TT genotype , rs651821 CC or TC genotype , rs2075291 GT + TT genotype ( P0.05 ) . The alleles associated with abnormal elevation of blood sugar include rs662799 G allele , rs651821 CC or TC genotype , rs2075291 GT + TT genotype ( P0.05 ) . The alleles associated with abnormal elevation of blood sugar include rs662799 G allele , rs651821 CC or TC genotype , rs2075291 GT + TT genotype ( P0.05 ) . The alleles associated with abnormal elevation of blood sugar include rs662799 G allele , rs651821 CC or TC genotype , rs2075291 GT + TT genotype ( P0.05 ) . The alleles associated with abnormal elevation of blood sugar include rs662799 G allele , rs651821 CC or TC genotype , rs2075291 GT + TT genotype ( P0.05 ) . The alleles associated with abnormal elevation of blood sugar include rs662799 G allele , rs651821 CC or TC genotype , rs2075291 GT + TT genotype ( P0.05 ) . The alleles associated with abnormal elevation of blood sugar include rs662799 G allele , rs651821 CC or TC genotype , rs2075291 GT + TT genotype ( P0.05 ) . The alleles associated with abnormal elevation of blood sugar include rs662799 G allele , rs651821 CC or TC genotype , rs2075291 GT + TT genotype ( P0.05 ) . The alleles associated with abnormal elevated blood glucose levels include rs662799 G allele , rs651821 CC or TC genotype , rs2075291 GT + TT genotype ( P0.05 ) . rs651821C allele and rs2075291 T allele ( P0.05 ) . The genotype associated with central obesity included rs5072 TC genotype , rs5128GC genotype , rs5104 GA genotype , rs662799 AA or GA genotype , rs651821 CC or TC genotype and rs2075291 GT + TT genotype ( P0.05 ) .
The prevalence of male was 36.64 % and the prevalence rate was 29.66 % .
The prevalence of APOA1 , APOC3 , APOA4 and APOA5 may be associated with abnormal factors of metabolic syndrome . APOA1 , APOC3 , APOA4 and APOA5 may be associated with abnormal factors of metabolic syndrome . APOA1 - APOC3 - APOA4 - APOA5 gene cluster may be associated with abnormal factors of metabolic syndrome .

【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R589
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本文编号：1821463