Background:Smoking is a risk factor for many human diseases. DNA methylation has been related to smoking, but genome-wide methylation data for smoking in Chinese populations is limited.Objectives:We aimed to investigate epigenome-wide methylation in relation to smoking in a Chinese population.Methods:We measured the methylation levels at > 485,000 CpG sites (CpGs) in DNA from leukocytes using a methylation array and conducted a genome-wide meta-analysis of DNA methylation and smoking in a total of 596 Chinese participants. We further evaluated the associations of smoking-related CpGs with internal polycyclic aromatic hydrocarbon (PAH) biomarkers and their correlations with the expression of corresponding genes.Results:We identified 318 CpGs whose methylation levels were associated with smoking at a genome-wide significance level (false discovery rate < 0.05), among which 161 CpGs annotated to 123 genes were not associated with smoking in recent studies of Europeans and African Americans. Of these smoking-related CpGs, methylation levels at 80 CpGs showed significant correlations with the expression of corresponding genes (including RUNX3, IL6R, PTAFR, ANKRD11, CEP135 and CDH23), and methylation at 15 CpGs was significantly associated with urinary 2-hydroxynaphthalene, the most representative internal monohydroxy-PAH biomarker for smoking.Conclusion:We identified DNA methylation markers associated with smoking in a Chinese population, including some markers that were also correlated with gene expression. Exposure to naphthalene, a byproduct of tobacco smoke, may contribute to smoking-related methylation.Citation:Zhu X, Li J, Deng S, Yu K, Liu X, Deng Q, Sun H, Zhang X, He M, Guo H, Chen W, Yuan J, Zhang B, Kuang D, He X, Bai Y, Han X, Liu B, Li X, Yang L, Jiang H, Zhang Y, Hu J, Cheng L, Luo X, Mei W, Zhou Z, Sun S, Zhang L, Liu C, Guo Y, Zhang Z, Hu FB, Liang L, Wu T. 2016. Genome-wide analysis of DNA methylation and cigarette smoking in Chinese. Environ Health Perspect 124:966–973; http://dx.doi.org/10.1289/ehp.1509834

Aims We report the results of long‐term follow‐up of the Pacing to Avoid Cardiac Enlargement (PACE) trial, a prospective, double‐blinded, randomized, multicentre study that confirmed the superiority of biventricular (BiV) pacing compared with right ventricular apical (RVA) pacing in prevention of LV adverse remodelling and deterioration of systolic function at 1 and 2 years. Methods and results Patients with bradycardia and preserved LVEF were randomized to receive RVA (n = 88) or BiV pacing (n = 89). Co‐primary endpoints were LV end‐systolic volume (LVESV) and LVEF measured by echocardiography. There were 149 patients who had extended follow‐up, with a mean duration of 4.8 ± 1.5 years (2.5–7.8 years). The primary endpoint analyses were performed in 146 patients (74 in the RVA group and 72 in the BiV group). In the RVA pacing group, the LVEF decreased while the LVESV increased progressively at follow‐up, but remained unchanged in the BiV pacing group. The differences in LVEF between the RVA and BiV groups were –6.3, –9.2, and –10.7% at 1‐year, 2‐year, and long‐term follow‐up, respectively (all P < 0.001). The corresponding differences in LVESV were +7.4, +9.9, and +13.1 mL, respectively (all P < 0.001). The deleterious effects of RVA pacing consistently occurred in all the pre‐defined subgroups. Furthermore, patients with RVA pacing had a significantly higher prevalence of heart failure hospitalization than the BiV group (23.9% vs. 14.6%, log‐rank χ2 = 7.55, P = 0.006). Conclusion Left ventricular adverse remodelling and deterioration of systolic function continued at long‐term follow‐up in patients with RVA pacing; this deterioration was prevented by the use of BiV pacing. Also, heart failure hospitalization was more prevalent in the RVA pacing group. Trial registration CUHK_CCT00037.

Our study identified novel blood methylation alterations associated with ACS and provided potential clinical biomarkers and therapeutic targets. Our results may suggest that immune signaling and cellular functions might be regulated at an epigenetic level in ACS.