SERPINA1 methylation and lung function in tobacco-smoke exposed European children and adults: a meta-analysis of ALEC population-based cohorts.
SERPINA1 methylation and lung function in tobacco-smoke exposed European children and adults: a meta-analysis of ALEC population-based cohorts.
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DOI：
10.1186/s12931-018-0850-8
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发表时间：
2018-08-22
影响因子：
5.8
通讯作者：
Probst-Hensch NM
中科院分区：
文献类型：
--
作者：
Beckmeyer-Borowko A;Imboden M;Rezwan FI;Wielscher M;Amaral AFS;Jeong A;Schaffner E;Auvinen J;Sebert S;Karhunen V;Bettschart R;Turk A;Pons M;Stolz D;Kronenberg F;Arathimos R;Sharp GC;Relton C;Henderson AJ;Jarvelin MR;Jarvis D;Holloway JW;Probst-Hensch NM
SERPINA1在呼吸健康中的病理生理作用可能更多地由其表达的调节决定，而不是由常见的遗传变异决定。一项以吸烟为主的成年人的家庭研究发现，SERPINA1基因中两个胞嘧啶-磷酸-鸟氨酸位点(CPGS)的甲基化与慢性阻塞性肺疾病的风险有关。这项研究的目的是通过测试SERPINA基因簇中的一组全面的CPGS，在普通人群样本中确认肺功能与SERPINA1甲基化的关联。我们考虑了来自三个欧洲人群的成年吸烟者的肺功能水平和下降，以及出生队列中暴露于烟草的儿童的肺功能水平和发育。使用Illumina Infinium人类甲基化450 K和EPIC珠片检测了1076名SAPALDIA、ECRHS和NFBC成人队列参与者以及259名ALSPAC儿童在两个时间点的DNA甲基化和肺功能。采用多因素横断面和纵向回归模型分析SERPINA基因簇(PP4R4-SERPINA13P)119个CpG位点甲基化与肺功能和循环α1-抗三聚体(AAT)的关系。位于SERPINA1下游32kb的SERPINA基因簇中cg08257009的甲基化与FEV1/FVC在成人中的Bonferroni校正水平相关，但在儿童中不相关。在校正多次检测后，SERPINA1基因中的甲基化信号均未显示与肺功能相关。结果不支持SERPINA1基因甲基化在烟草烟雾暴露的普通人群中作为整个生命过程中肺功能的决定因素的作用。本文的在线版本(10.1186/s12931-0180850-8)包含向授权用户提供的补充材料。
The pathophysiological role of SERPINA1 in respiratory health may be more strongly determined by the regulation of its expression than by common genetic variants. A family based study of predominantly smoking adults found methylation at two Cytosine-phosphate-Guanine sites (CpGs) in SERPINA1 gene to be associated with chronic obstructive pulmonary disease risk. The objective of this study was to confirm the association of lung function with SERPINA1 methylation in general population samples by testing a comprehensive set of CpGs in the SERPINA gene cluster. We considered lung function level and decline in adult smokers from three European population-based cohorts and lung function level and growth in tobacco-smoke exposed children from a birth cohort. DNA methylation using Illumina Infinium Human Methylation 450 k and EPIC beadchips and lung function were measured at two time points in 1076 SAPALDIA, ECRHS and NFBC adult cohort participants and 259 ALSPAC children. Associations of methylation at 119 CpG sites in the SERPINA gene cluster (PP4R4-SERPINA13P) with lung functions and circulating alpha-1-antitripsin (AAT) were assessed using multivariable cross-sectional and longitudinal regression models. Methylation at cg08257009 in the SERPINA gene cluster, located 32 kb downstream of SERPINA1, not annotated to a gene, was associated with FEV1/FVC at the Bonferroni corrected level in adults, but not in children. None of the methylation signals in the SERPINA1 gene showed associations with lung function after correcting for multiple testing. The results do not support a role of SERPINA1 gene methylation as determinant of lung function across the life course in the tobacco smoke exposed general population exposed. The online version of this article (10.1186/s12931-018-0850-8) contains supplementary material, which is available to authorized users.
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影响因子：
3.8
作者：
Lee MK;Hong Y;Kim SY;Kim WJ;London SJ
通讯作者：
London SJ
影响因子：
2.9
作者：
Lutz SM;Cho MH;Young K;Hersh CP;Castaldi PJ;McDonald ML;Regan E;Mattheisen M;DeMeo DL;Parker M;Foreman M;Make BJ;Jensen RL;Casaburi R;Lomas DA;Bhatt SP;Bakke P;Gulsvik A;Crapo JD;Beaty TH;Laird NM;Lange C;Hokanson JE;Silverman EK;ECLIPSE Investigators;COPDGene Investigators
通讯作者：
COPDGene Investigators
DOI：
10.1007/s00038-005-4075-5
发表时间：
2005-01-01
期刊：
SOZIAL-UND PRAVENTIVMEDIZIN
影响因子：
--
作者：
Ackermann-Liebrich, U;Kuna-Dibbert, B;Leuenberger, P
通讯作者：
Leuenberger, P
影响因子：
11.5
作者：
Russo, AL;Thiagalingam, A;Thiagalingam, S
通讯作者：
Thiagalingam, S
影响因子：
3.5
作者：
Stueve，Theresa Ryan;Li，Wen-Qing;Landi，Maria Teresa
通讯作者：
Landi，Maria Teresa