基因-环境交互作用对动脉僵硬度影响的家系研究  

Genotype-environment interaction on arterial stiffness:A pedigree-based study

作　　者：王雪珩 王斯悦 彭和香 范梦 郭煌达 侯天姣 王梦莹[1] 武轶群[1] 秦雪英[1] 唐迅[1] 李劲[1] 陈大方[1] 胡永华[1] 吴涛[1,2] WANG Xue-heng;WANG Si-yue;PENG He-xiang;FAN Meng;GUO Huang-da;HOU Tian-jiao;WANG Meng-ying;WU Yi-qun;QIN Xue-ying;TANG Xun;LI Jin;CHEN Da-fang;HU Yong-hua;WU Tao(Department of Epidemiology and Biostatistics,Peking University School of Public Health,Beijing 100191,China;Key Laboratory of Epidemiology of Major Diseases,Ministry of Education,Beijing 100191,China)

机构地区：[1]北京大学公共卫生学院流行病与卫生统计学系,北京100191 [2]重大疾病流行病学教育部重点实验室,北京100191

出　　处：《北京大学学报（医学版）》2023年第3期400-407,共8页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金(82204135);北京市自然科学基金(7232237);中国博士后科学基金(BX2021021,2022M710249)。

摘　　要：目的:利用北京房山家系队列研究的基线调查数据,探索基因-环境交互作用对动脉僵硬度的影响。方法:选取来自北京市房山区9个乡镇的先证者及其亲属作为研究对象,以吸烟、饮酒、体重指数(body mass index,BMI)、膳食评分和体力活动作为行为生活方式因素,以肱-踝脉搏波传导速度(brachial-ankle pulse wave velocity,baPWV)和踝肱指数(ankle-brachial index,ABI)作为动脉僵硬度评价指标,采用方差组分模型估计动脉僵硬度的遗传度,利用极大似然法进行基因型-环境交互作用分析。基于基因型-环境交互作用分析识别的阳性环境因素,进一步选取糖脂代谢通路上的45个基因位点作为候选基因位点,利用广义估计方程模型,探索基因位点与生活方式间的交互作用对动脉僵硬度的影响。结果:共纳入了来自3225个家系的6302名研究对象,研究对象的平均年龄为56.9岁,男性占比45.1%。估计得到baPWV和ABI的遗传度分别为0.360(95%CI:0.302~0.418)和0.243(95%CI:0.175~0.311)。基因型-环境交互作用结果显示,总体加性遗传效应与年龄、性别、膳食评分和BMI间存在交互作用,分别影响baPWV和ABI水平。以baPWV作为结局评价指标时,ADAMTS9-AS2基因上和CDH13基因上的2个单核苷酸多态性(single nucleotide polymorphism,SNP)位点均与膳食评分存在交互作用。高遗传风险的个体遵循健康的生活方式能够降低其动脉僵硬程度。以ABI作为研究终点时,CDKAL1、ATP8B2和SLC30A8基因上的3个SNP位点与BMI存在交互作用,影响动脉僵硬度水平。对于高遗传风险的个体,保持健康的BMI水平能够有效降低动脉僵硬度水平。结论:本研究利用家系关系观察了基因型-健康膳食模式和基因型-BMI交互作用影响动脉僵硬度水平,发现5个SNP位点与二者存在交互作用;维持健康的生活方式和健康的BMI水平能够降低遗传因素对动脉僵硬度的影响,为识别动脉僵硬度的环境危�Objective:To utilized the baseline data of the Beijing Fangshan Family Cohort Study,and to estimate whether the association between a healthy lifestyle and arterial stiffness might be modified by genetic effects.Methods:Probands and their relatives from 9 rural areas in Fangshan district,Beijing were included in this study.We developed a healthy lifestyle score based on five lifestyle behaviors:smoking,alcohol consumption,body mass index(BMI),dietary pattern,and physical activity.The measurements of arterial stiffness were brachial-ankle pulse wave velocity(baPWV)and ankle-brachial index(ABI).A variance component model was used to determine the heritability of arterial stiffness.Genotype-environment interaction effects were performed by the maximum likelihood methods.Subsequently,45 candidate single nucleotide polymorphisms(SNPs)located in the glycolipid metabolism pathway were selected,and generalized estimated equations were used to assess the gene-environment interaction effects between particular genetic loci and healthy lifestyles.Results:A total of 6302 study subjects across 3225 pedigrees were enrolled in this study,with a mean age of 56.9 years and 45.1%male.Heritability of baPWV and ABI was 0.360(95%CI:0.302-0.418)and 0.243(95%CI:0.175-0.311),respectively.Significant genotype-healthy diet interaction on baPWV and genotype-BMI interaction on ABI were observed.Following the findings of genotype-environment interaction analysis,we further identified two SNPs located in ADAMTS9-AS2 and CDH13 might modify the association between healthy dietary pattern and arterial stiffness,indicating that adherence to a healthy dietary pattern might attenuate the genetic risk on arterial stiffness.Three SNPs in CDKAL1,ATP8B2 and SLC30A8 were shown to interact with BMI,implying that maintaining BMI within a healthy range might decrease the genetic risk of arterial stiffness.Conclusion:The current study discovered that genotype-healthy dietary pattern and genotype-BMI interactions might affect the risk of arterial stiffness.F

关 键 词：血管硬化程度 基因-环境相互作用 生活方式 系谱 

分 类 号：R394[医药卫生—医学遗传学]