1.
An updated meta-analysis showed smoking modify the association of GSTM1 null genotype on the risk of coronary heart disease.
Song, Y, Shan, Z, Liu, X, Chen, X, Luo, C, Chen, L, Wang, Y, Gong, L, Liu, L, Liang, J
Bioscience reports. 2021;(2)
Abstract
Background Oxidative stress is considered to be involved in the pathogenesis of coronary heart disease (CHD). Glutathione-S-transferase (GST) enzymes play important roles in antioxidant defenses and may influence CHD risk. The present meta-analysis was performed to investigate the link between glutathione S-transferase M1 (GSTM1) null genotype and CHD and to get a precise evaluation of interaction between GSTM1 null genotype and smoking by the case-only design. Methods PubMed and EMBASE databases were searched through 15 December 2020 to retrieve articles. Odds ratios (ORs) were pooled using either fixed-effects or random-effects models. Results Thirty-seven studies showed that GSTM1 null genotype was associated with risk of CHD in total population, Caucasians and Asians (for total population, OR = 1.38, 95% confidence interval (CI): 1.15, 1.65; for Caucasians, OR = 1.34, 95% CI: 1.04, 1.72; for Asians, OR = 1.40, 95% CI: 1.11, 1.77). After adjustment for heterogeneity, these relationships were still significant. After adjustment for heterogeneity, case-only analysis of 11 studies showed a positive multiplicative interaction between GSTM1 null genotype and smoking (ever smoking vs. never smoking) (OR = 1.27, 95% CI: 1.08, 1.50; I2 = 0%, P=0.553). Conclusions The overall results indicated that GSTM1 null genotype was associated with a higher risk of CHD, and the association may be affected by smoking status. This is the first meta-analysis to prove a positive effect of the interaction between GSTM1 null genotype and smoking status on the risk of CHD. Well-designed studies are needed to investigate the possible gene-gene or gene-environment interactions.
2.
Smoking quantity determines disease activity and function in Chinese patients with ankylosing spondylitis.
Zhang, H, Wan, W, Liu, J, Dai, S, Zou, Y, Qian, Q, Ding, Y, Xu, X, Ji, H, He, H, et al
Clinical rheumatology. 2018;(6):1605-1616
Abstract
The objective of this study was to systemically and comprehensively evaluate the associations between smoking and disease outcomes in patients with ankylosing spondylitis (AS). Information on smoking, clinical features, and sociodemographic characteristics was collected by a questionnaire administered directly to the patient. Group differences were analyzed by t test or chi-square test. Logistic regression analysis was conducted with the Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), C-reactive protein, and erythrocyte sedimentation rate as the dependent variables and different stratification of smoking duration, smoking intensity, and cumulative smoking as independent variables. In order to compare our results with previous studies, meta-analysis was performed to calculate standardized mean difference (SMD) for relationship between outcomes and smoking status. A total of 1178 AS patients were analyzed. Compared with non-smokers, the risk of having active disease (BASDAI ≥ 4) was higher in patients who smoked at least 15 years, or 15 cigarettes per day, or 15 pack-years (OR = 1.70 [1.06, 2.73], 1.75 [1.08, 2.82], and 1.97 [1.06, 3.67], respectively); and smokers had increasing risk of BASDAI ≥ 4 with increasing years of smoking, or cigarettes per day, or pack-years (p-trend = 0.010, 0.008 and 0.006, respectively). The risk of having active disease was higher in patients who smoked at least 15 cigarettes per day or 15 pack-years (OR = 1.74 [1.06, 2.84] and 2.89 [1.56, 5.35], respectively), with increasing number of cigarettes per day and pack-years. Smokers had an increased risk of BASFI ≥ 4 (p-trend = 0.040 and 0.007, respectively). By meta-analysis, current, former and ever smokers had significantly higher BASDAI (SMD = 0.34 [0.18, 0.48], 0.10 [0.01, 0.19], and 0.27 [0.20, 0.34], respectively) and BASFI (SMD = 0.35 [0.16, 0.55], 0.30 [0.22, 0.39], and 0.35 [0.21, 0.50], respectively) compared to non-smokers. Smoking is a risk factor for greater disease activity and worse functioning in AS patients.
3.
Genome-Wide Meta-Analysis of Cotinine Levels in Cigarette Smokers Identifies Locus at 4q13.2.
Ware, JJ, Chen, X, Vink, J, Loukola, A, Minica, C, Pool, R, Milaneschi, Y, Mangino, M, Menni, C, Chen, J, et al
Scientific reports. 2016;:20092
Abstract
Genome-wide association studies (GWAS) of complex behavioural phenotypes such as cigarette smoking typically employ self-report phenotypes. However, precise biomarker phenotypes may afford greater statistical power and identify novel variants. Here we report the results of a GWAS meta-analysis of levels of cotinine, the primary metabolite of nicotine, in 4,548 daily smokers of European ancestry. We identified a locus close to UGT2B10 at 4q13.2 (minimum p = 5.89 × 10(-10) for rs114612145), which was consequently replicated. This variant is in high linkage disequilibrium with a known functional variant in the UGT2B10 gene which is associated with reduced nicotine and cotinine glucuronidation activity, but intriguingly is not associated with nicotine intake. Additionally, we observed association between multiple variants within the 15q25.1 region and cotinine levels, all located within the CHRNA5-A3-B4 gene cluster or adjacent genes, consistent with previous much larger GWAS using self-report measures of smoking quantity. These results clearly illustrate the increase in power afforded by using precise biomarker measures in GWAS. Perhaps more importantly however, they also highlight that biomarkers do not always mark the phenotype of interest. The use of metabolite data as a proxy for environmental exposures should be carefully considered in the context of individual differences in metabolic pathways.