过氧化物酶体增殖物激活受体α基因单核苷酸多态性及单体型与脂蛋白a关联的研究  

Association between polymorphisms, haplotypes of peroxisome proliferators activated receptor α gene and the level of lipoprotein （a）

作　　者：解惠坚[1] 海波[1] 郭志荣[1] 周正元[2] 刘萌萌[1] 武鸣[3] 

机构地区：[1]苏州大学医学部公共卫生学院流行病与卫生统计教研室,215123 [2]江苏省常熟市疾病预防控制中心 [3]江苏省疾病预防控制中心

出　　处：《中华流行病学杂志》2014年第7期787-791,共5页Chinese Journal of Epidemiology

基　　金：卫生部科学研究基金（WKJ2004-2-014）

摘　　要：目的 分析过氧化物酶体增殖物激活受体（PPAR）α基因3个单核苷酸多态性（SNP）L 162V （rs 1800206）、7G＞C（rs4253778）和1A＞C（rs135539）与脂蛋白a[Lp（a）]的关联,并通过构建单体型进一步分析PPARα基因对Lp（a）水平的调控.方法 采用单纯随机抽样方法抽取“江苏省多代谢异常和代谢综合征防治研究（PMMJS）”队列人群中644名研究对象,对其基线血样本进行PPARα基因多态性检测.利用x2检验确定人群是否符合Hardy-Weinberg遗传平衡定律,运用线性回归模型分析单个SNP与Lp（a）的关联.采用SNPstats软件构建3个SNP的单体型并进行关联分析.结果 调整性别、年龄、吸烟、饮酒和BMI后,显性模型结果显示,与野生纯合子（LL）相比,携带162V等位基因（LV＋VV）Lp（a）水平平均升高57.70 mg/L（95％CI：32.03 ～ 83.37 mg/L）,P＜0.001.共显性模型中,162V杂合子（LV）与野生纯合子相比,Lp（a）水平平均升高60.25 mg/L（95％CI：34.18～86.33mg/L）,P＜0.001.与频率最高的单体型A-G-L（1A＞C,7G＞C,L162V）相比,携带单体型A-G-V和单体型C-G-V分别升高Lp（a）水平41.87 mg/L和51.48 mg/L,P值分别为0.012 0和0.009 7.结论 162V等位基因携带与升高的Lp（a）水平有显著关联,单体型A-G-V和C-G-V可能是影响Lp（a）的危险因子,PPARα基因是调控Lp（a）的重要遗传标记.Objective The aim of this study was to investigate the association between three single-nucleotide polymorphisms （SNP） of in the peroxisome proliferator-activated receptor （PPAR）α gene and the level of lipoprotein （a） [Lp （a）].Methods Participants were recruited under the framework of a cohort populations survey from the PMMJS （Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province） which was conducted in the urban community of Jiangsu province from 1999 to 2007.644 subjects （234 males,410 females） were randomly selected and genotyped for three polymorphisms which were used as genetic marker for PPARα gene （rs 1800206,rs4253778 and rs135539）.Data related to individual polymorphism and haplotype were available for analysis.x2 test was used to determine if the whole population was in Hardy-Weinberg genetic equilibrium.Linear regression models were used to analyze the association between SNPs in PPARα gene and the level of Lp（a）.Associations between PPARα haplotypes and serum Lp（a） levels were analyzed by the SNPstats software.Results In the dominant model,after factors as sex,age,smoking,alcohol and BMI were adjusted,the presence of the V162 allele of L162V appeared associated with a high level of Lp（a） （mean difference was 57.70 mg/L（95％CI：32.03-83.37 mg/L）,P＜0.001.Data from the haplotype analysis revealed that A-G-V and C-G-V haplotype （established by 1A＞C,7G＞C L162V） were significantly associated with a higher level of Lp（a） （P=0.012 0 and 0.009 7）.Conclusion Results from our study might help to clarify the role ofPPARα gene in regulation of Lp （a） and the evaluation of its polymorphisms and haplotypes which were characterized as genetic factors for Lp （a）.

关 键 词：过氧化物酶体增殖物激活受体 脂蛋白A 单体型 单核苷酸多态性 

分 类 号：R589[医药卫生—内分泌]