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险因素、制定人群精准预防控制策略提供了一定的研究基础和思路。
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.Furthermore,we identified five genetic loci that might modify the relationship between healthy dietary pattern and BMI with arterial stiffness.Our findings suggested that a healthy lifestyle may reduce the genetic risk of arterial stiffness.This study has laid the groundwork for future research exploring mechanisms of arterial stiffness.
作者
王雪珩
王斯悦
彭和香
范梦
郭煌达
侯天姣
王梦莹
武轶群
秦雪英
唐迅
李劲
陈大方
胡永华
吴涛
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)
出处
《北京大学学报（医学版）》
CAS
CSCD
北大核心
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)。
