吸烟、围产期吸烟导致端粒长度变化的风险

职业与健康 ›› 2025, Vol. 41 ›› Issue (3): 328-335.

吸烟、围产期吸烟导致端粒长度变化的风险

夏晓晓¹, 李伦兰^1,2, 丁佩佩¹, 王婷¹, 陈孟孟¹

1.安徽医科大学护理学院,安徽合肥 230032;
2.安徽医科大学第一附属医院人力资源部,安徽合肥 230022

收稿日期:2024-04-30 修回日期:2024-05-13 出版日期:2025-02-01 发布日期:2025-12-17
通信作者: 李伦兰,主任护师,E-mail：lilunlan@aliyun.com
作者简介:夏晓晓,女,在读硕士研究生,研究方向为骨科护理。
基金资助:
安徽高校自然科学研究项目（KJ2020ZD18）

Risk of telomere length changes due to smoking,perinatal smoking

XIA Xiaoxiao¹, LI Lunlan^1,2, DING Peipei¹, WANG Ting¹, CHEN Mengmeng¹

1. School of Nursing,Anhui Medical University,Hefei,Anhui 230032,China;
2. Department of Human Resources,First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230022,China

Received:2024-04-30 Revised:2024-05-13 Online:2025-02-01 Published:2025-12-17
Contact: LI Lunlan,Chief nurse,E-mail：lilunlan@aliyun.com

摘要/Abstract

摘要： 目的采用2项两样本孟德尔随机化（Mendelian randomization,MR）探讨吸烟、围产期吸烟导致端粒长度变化的风险。方法将全基因组关联研究（genome-wideassociation study,GWAS）中吸烟（2018年）、围产期吸烟（2018年）的遗传数据作为工具变量分别与GWAS中端粒长度（2021年）的遗传数据进行两样本MR分析,主要采用逆方差加权法（inverse-variance weighted,IVW）进行分析,并以加权中位数法（weighted median estimator,WME）、基于Egger回归的孟德尔随机化（Mendelian randomization-egger regression,MR-Egger）等进行补充。根据比值比（odds ratio,OR）和95%CI评估相比于不吸烟者,吸烟、围产期吸烟导致端粒长度变化的风险,通过比较两者OR值推断相对于吸烟者,围产期吸烟导致端粒长度变化的风险。采用Cochran’s Q检验、MR-Egger截距法、MR-PRESSO、去一法进行敏感性分析。结果共筛选出35个与吸烟相关的单核苷酸多态性（single nucleotide polymorphism,SNP）和16个与围产期吸烟密切相关的SNP作为工具变量,IVW结果显示,相比于不吸烟者,吸烟、围产期吸烟导致端粒长度变短的风险约增加25%[OR=0.75（95%CI：0.66~0.85）,P<0.05]和37%[OR=0.63（95%CI：0.52~0.76）,P<0.05],相对于吸烟者来说,围产期吸烟导致端粒长度变短的风险可能有所增加,WME结果验证了此推测[OR=0.77（95%CI：0.67~0.89）,P<0.05;OR=0.67（95%CI：0.53~0.85）,P<0.05]。MR-Egger法和MR-PRESSO均未发现2项MR结果存在水平多效性（均P>0.05）;Cochran’s Q结果均显示可能存在一定异质性（均P<0.05）,但漏斗图均未发现显著异质性。结论遗传学预测,相比于不吸烟者,吸烟、围产期吸烟均与端粒长度变短的风险相关,相比于吸烟者,围产期吸烟更有可能导致端粒长度变短。

关键词: 围产期, 吸烟, 端粒长度, 孟德尔随机化, 风险预测

Abstract: Objective To explore the risk of telomere length changes due to smoking,perinatal smoking by two two-sample Mendelian randomization（MR）. Methods The genetic data of smoking（2018） and perinatal smoking（2018） from the genome-wide association study（GWAS） were used as instrumental variables,and the genetic data of telomere length from the GWAS（2021） were used for two-sample MR analysis. The inverse variance weighting（IVW） method was used for the analysis,and the weighted median method（WME） and Mendelian randomization-egger（MR-Egger） regression method were used as supplements. The odds ratio（OR） and 95%CI were used to estimate the risk of telomere length change caused by smoking and perinatal smoking compared with non-smokers.The OR value was used to estimate the risk of telomere length change caused by perinatal smoking compared with smokers. The Cochran's Q test,MR-Egger intercept method,MR-PRESSO and leave-one-out method were used for sensitivity analysis. Results A total of 35 single nucleotide polymorphisms（SNP） associated with smoking and 16 SNP closely associated with perinatal smoking were screened as instrumental variables. The IVW results showed that compared with non-smokers,the risk of shorter telomere length was increased by 25%[OR=0.75（95%CI：0.66-0.85）,P<0.05] and 37%[OR=0.63（95%CI：0.52-0.76）,P<0.05] for smoking and perinatal smoking,respectively.Compared with smokers,perinatal smoking may increase the risk of shorter telomere length,and this speculation was verified by WME results[OR=0.77（95%CI：0.67-0.89）,P<0.05;OR=0.67（95%CI：0.53-0.85）,P<0.05]. The MR-Egger method and MR-PRESSO did not find horizontal pleiotropy of the two MR results（both P>0.05）. The Cochran's Q results showed that there may be some heterogeneity（all P<0.05）,but the funnel plot did not find significant heterogeneity. Conclusion The genetic prediction shows that smoking and perinatal smoking are associated with the risk of shorter telomere length compared with non-smokers.Compared with smokers,perinatal smoking is more likely to lead to shorter telomere length.

Key words: Perinatal period, Smoking, Telomere length, Mendelian randomization, Risk prediction

中图分类号:

R394.6

夏晓晓, 李伦兰, 丁佩佩, 王婷, 陈孟孟. 吸烟、围产期吸烟导致端粒长度变化的风险. [J]职业与健康, 2025, 41(3): 328-335.

XIA Xiaoxiao, LI Lunlan, DING Peipei, WANG Ting, CHEN Mengmeng. Risk of telomere length changes due to smoking,perinatal smoking. [J]OCCUPATION AND HEALTH, 2025, 41(3): 328-335.

参考文献

[1] ASTUTI Y,WARDHANA A,WATKIN J,et al.Cigarette smoking and telomere length:A systematic review of 84 studies and meta-analysis[J].Environ Res,2017,158:480-489.
[2] LIU J,WANG L,WANG Z,et al.Roles of telomere biology in cell senescence,replicative and chronological ageing[J].Cells,2019,8(1):54.
[3] 张宇宁. HK1通过与TERT结合抑制端粒酶活性调控肺腺癌细胞衰老[D].吉林:吉林大学,2023.
[4] SCHNEIDER C V,SCHNEIDER K M,TEUMER A,et al.Association of telomere length with risk of disease and mortality[J].JAMA Intern Med,2022,182(3):291-300.
[5] TOPIWALA A,TASCHLER B,EBMEIER K P,et al.Alcohol consumption and telomere length:Mendelian randomization clarifies alcohol's effects[J].Mol Psychiatry,2022,27(10):4001-4008.
[6] ZEINOUN B,TEIXEIRA M T,BARASCU A.TERRA and telomere maintenance in the yeast saccharomyces cerevisiae[J].Genes,2023, 14(3):618.
[7] LIBERTINI G,SHUBERNETSKAYA O,CORBI G,et al.Is evidence supporting the subtelomere-telomere theory of aging?[J].Biochemistry (Mosc),2021,86(12):1526-1539.
[8] 谭兵兵,赵莉,成果,等.行为生活方式对端粒长度影响的研究进展[J].现代预防医学,2021,48(22):4152-4157.
[9] FLANNAGAN K S,JANSEN E C,ROZEK L S,et al.Sociodemographic correlates and family aggregation of leukocyte telomere length in adults and children from Mesoamerica[J].Am J Hum Biol,2017,29(3):e22942.
[10] YUN M,LI S,YAN Y,et al.Suppression effect of body weight on the association between cigarette smoking and telomere length:the Bogalusa Heart Study[J].Aging(Albany NY),2019,11(21):9893-9900.
[11] SABERI S,KALLOGER S E,ZHU M M T,et al.Dynamics of leukocyte telomere length in pregnant women living with HIV,and HIV-negative pregnant women:A longitudinal observational study[J].PLoS One,2019,14(3):e0212273.
[12] LIU B,SONG L,ZHANG L,et al.Prenatal second-hand smoke exposure and newborn telomere length[J].Pediatr Res,2020,87(6):1081-1085.
[13] LAMINA C.Mendelian Randomization:Principles and its usage in Lp(a)research[J].Atherosclerosis,2022,349:36-41.
[14] LI J,LI C,HUANG Y,et al.Mendelian randomization analyses in ocular disease:A powerful approach to causal inference with human genetic data[J].J Transl Med,2022,20(1):1-19.
[15] 刘晓田,屠润琪,何亚玲,等.JAK2基因甲基化与肥胖因果关联的孟德尔随机化研究[J].中华流行病学杂志,2022,43(8):1315-1320.
[16] CODD V,WANG Q,ALLARA E,et al.Polygenic basis and biomedical consequences of telomere length variation[J].Nat Genet,2021,53(10):1425-1433.
[17] 丁佳豪,章梦琦,郝明霞,等.孟德尔随机化研究精神分裂症与自杀或故意自残的因果关系[J].中华精神科杂志,2023,56(1):32-39.
[18] SAWHNEY V,CAMPBELL N G,BROUILETTE S W,et al.Telomere shortening and telomerase activity in ischaemic cardiomyopathy patients-potential markers of ventricular arrhythmia[J].Int J Cardiol,2016
207:157-163.
[19] WULANINGSIH W,SERRANO F E,UTARINI A,et al.Smoking,second-hand smoke exposure and smoking cessation in relation to leukocyte telomere length and mortality[J].Oncotarget,2016,7(37):60419-60431.
[20] KAWANISHI S,OIKAWA S.Mechanism of telomere shortening by oxidative stress[J].Ann N Y Acad Sci,2004,1019:278-284.
[21] REICHERT S,STIER A.Does oxidative stress shorten telomeres in vivo? A review[J].Biol Lett,2017,13(12):20170463.
[22] CATTAN V,MERCIER N,GARDNER J P,et al.Chronic oxidative stress induces a tissue-specific reduction in telomere length in CAST/Ei mice[J].Free Radic Biol Med,2008,44(8):1592-1598.
[23] SANDERS J L,IANNACCONE A,BOUDREAU R M,et al.The association of cataract with leukocyte telomere length in older adults:Defining a new marker of aging[J].J Gerontol A Biol Sci Med Sci,2011, 66(6):639-645.
[24] ZHANG J,RANE G,DAI X,et al.Ageing and the telomere connection:An intimate relationship with inflammation[J].Ageing Res Rev,2016,25:55-69.
[25] DO E K,NICKSIC N E,CLIFFORD J S,et al.Perceived harms of and exposure to tobacco use and current tobacco use among reproductive-aged women from the PATH study[J].Women Health,2020,60(9):1040-1051.
[26] MUEZZINLER A,MONS U,DIEFFENBACH A K,et al.Smoking habits and leukocyte telomere length dynamics among older adults:Results from the ESTHER cohort[J].Exp Gerontol,2015,70:18-25.
[27] NAWROT T S,STAESSEN J A,HOLVOET P,et al.Telomere length and its associations with oxidized-LDL,carotid artery distensibility and smoking[J].Front Biosci(Elite Ed),2010,2(3):1164-1168.
[28] CHIBA T,OMORI A,TAKAHASHI K,et al.Correlations between the detection of stress-associated hormone/oxidative stress markers in umbilical cord blood and the physical condition of the mother and neonate[J].J Obstet Gynaecol Res,2010,36(5):958-964.
[29] TANA M,TIRONE C,AURILIA C,et al.Respiratory management of the preterm infant:supporting evidence-based practice at the bedside[J].Children(Basel),2023,10(3):535.
[30] GEORGESON G D,SZONY B J,STREITMAN K,et al.Antioxidant enzyme activities are decreased in preterm infants and in neonates born via caesarean section[J].Eur J Obstet Gynecol Reprod Biol,2002
103(2):136-139.
[31] ADEOYE O,OLAWUMI J,OPEYEMI A,et al.Review on the role of glutathione on oxidative stress and infertility[J].JBRA Assist Reprod,2018,22(1):61-66.
[32] KARACOR T,SAK S,BASARANOGLU S,et al.Assessment of oxidative stress markers in cord blood of newborns to patients with oxytocin-induced labor[J].J Obstet Gynaecol Res,2017,43(5):860-865.
[33] WILINSKA M,BORSZEWSKA-KORNACKA M K,NIEMIEC T,et al.Oxidative stress and total antioxidant status in term newborns and their mothers[J].Ann Agric Environ Med,2015,22(4):736-740.
[34] VENTO M,AGUAR M,ESCOBAR J,et al.Antenatal steroids and antioxidant enzyme activity in preterm infants:Influence of gender and timing[J].Antioxid Redox Signal,2009,11(12):2945-2955.
[35] SHOJI H,KOLETZKO B.Oxidative stress and antioxidant protection in the perinatal period[J].Curr Opin Clin Nutr Metab Care,2007,10(3):324-328.
[36] GITTO E,PELLEGRINO S,D'ARRIGO S,et al.Oxidative stress in resuscitation and in ventilation of newborns[J].Eur Respir J,2009,34(6):1461-1469.