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户外空气污染与心血管健康研究中老年男性 Y 染色体缺失

Outdoor air pollution and mosaic loss of chromosome Y in older men from the Cardiovascular Health Study.

机构信息

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.

Department of Internal Medicine, School of Medicine, University of California, Davis, CA, USA.

出版信息

Environ Int. 2018 Jul;116:239-247. doi: 10.1016/j.envint.2018.04.030. Epub 2018 Apr 24.

Abstract

BACKGROUND

Mosaic loss of chromosome Y (mLOY) can occur in a fraction of cells as men age, which is potentially linked to increased mortality risk. Smoking is related to mLOY; however, the contribution of air pollution is unclear.

OBJECTIVE

We investigated whether exposure to outdoor air pollution, age, and smoking were associated with mLOY.

METHODS

We analyzed baseline (1989-1993) blood samples from 933 men ≥65 years of age from the prospective Cardiovascular Health Study. Particulate matter ≤10 μm (PM), carbon monoxide, nitrogen dioxide, sulfur dioxide, and ozone data were obtained from the U.S. EPA Aerometric Information Retrieval System for the year prior to baseline. Inverse-distance weighted air monitor data were used to estimate each participants' monthly residential exposure. mLOY was detected with standard methods using signal intensity (median log-R ratio (mLRR)) of the male-specific chromosome Y regions from Illumina array data. Linear regression models were used to evaluate relations between mean exposure in the prior year, age, smoking and continuous mLRR.

RESULTS

Increased PM was associated with mLOY, namely decreased mLRR (p-trend = 0.03). Compared with the lowest tertile (≤28.5 μg/m), the middle (28.5-31.0 μg/m; β = -0.0044, p = 0.09) and highest (≥31 μg/m; β = -0.0054, p = 0.04) tertiles had decreased mLRR, adjusted for age, clinic, race/cohort, smoking status and pack-years. Additionally, increasing age (β = -0.00035, p = 0.06) and smoking pack-years (β = -0.00011, p = 1.4E-3) were associated with decreased mLRR, adjusted for each other and race/cohort. No significant associations were found for other pollutants.

CONCLUSIONS

PM may increase leukocyte mLOY, a marker of genomic instability. The sample size was modest and replication is warranted.

摘要

背景

随着男性年龄的增长,染色体 Y 的部分缺失(mLOY)可能会在一部分细胞中发生,这可能与死亡率的增加有关。吸烟与 mLOY 有关;然而,空气污染的贡献尚不清楚。

目的

我们研究了户外空气污染、年龄和吸烟是否与 mLOY 有关。

方法

我们分析了前瞻性心血管健康研究中 933 名年龄≥65 岁男性的基线(1989-1993 年)血液样本。颗粒物≤10μm(PM)、一氧化碳、二氧化氮、二氧化硫和臭氧数据是从美国环境保护署空气质量信息检索系统中获取的,这些数据是在基线前一年获得的。使用反距离加权空气监测数据来估计每个参与者的每月住宅暴露量。使用 Illumina 阵列数据的男性特异性染色体 Y 区域的信号强度(中位数对数比率(mLRR))来检测 mLOY。线性回归模型用于评估前一年的平均暴露、年龄、吸烟与连续 mLRR 之间的关系。

结果

PM 增加与 mLOY 有关,即 mLRR 降低(p 趋势=0.03)。与最低三分位(≤28.5μg/m)相比,中间三分位(28.5-31.0μg/m;β=-0.0044,p=0.09)和最高三分位(≥31μg/m;β=-0.0054,p=0.04)的 mLRR 降低,调整了年龄、诊所、种族/队列、吸烟状况和吸烟包年数。此外,年龄增加(β=-0.00035,p=0.06)和吸烟包年数(β=-0.00011,p=1.4E-3)与 mLRR 降低有关,调整了彼此和种族/队列。其他污染物没有发现显著的相关性。

结论

PM 可能会增加白细胞 mLOY,这是基因组不稳定性的一个标志。样本量较小,需要进行复制。

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