Graduate Program in Dentistry, Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brazil.
Departments of Oral Biology and Pediatric Dentistry, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.
PLoS One. 2019 Apr 11;14(4):e0214946. doi: 10.1371/journal.pone.0214946. eCollection 2019.
Smoking is a leading cause of preventable death. The effect of tobacco is even more contundent in people with mental illness and, in general, cigarette smoking addiction is influenced by genetic factors. The opioid system is involved in the mesolimbic reward system, which is of great importance in addictive behaviors, such as smoking and is influenced by genes such as the OPRM1. The aim of this study was to evaluate if selecting a comparison group that include light smokers versus people that never smoked impacts the results of genetic association studies. In addition, to evaluate the genetic association in different groups of smokers by analyzing independent covariates such as mental illness and clinical dental data. All subjects were participants of the Dental Registry and DNA Repository project. Genotyping was carried out using TaqMan chemistry for two markers in OPRM1 (rs553202 and rs7755635). Logistic regression analyses were performed as implemented in PLINK. The established value for alpha was 5%, and the Hardy-Weinberg equilibrium was evaluated by the chi-square test with one degree of freedom for each marker. 1,897 patients were included, which were allocated to eight distinct groups, according to the frequency and quantity of cigarettes smoked and mental illness status. There was no significant association between the two markers in OPRM1 and smoking. When mental illness and dental clinical data (tooth loss, dental caries, and periodontitis) were used as covariates, there were associations between heavy smoking and OPRM1, when non-smokers were used as comparison. We did not have diet or microbiome data to consider for these dental analyses and suggest that these kinds of data should be always incorporated in the future. Significant results were found only when the covariables mental illness and oral clinical data were added to the analysis.
吸烟是可预防死亡的主要原因。烟草的影响在精神病患者中更为明显，一般来说，吸烟成瘾受遗传因素影响。阿片系统参与中脑边缘奖励系统，该系统在吸烟等成瘾行为中非常重要，并且受 OPRM1 等基因的影响。本研究旨在评估选择包括轻度吸烟者与从不吸烟者的对照组是否会影响遗传关联研究的结果。此外，通过分析精神疾病和临床牙科数据等独立协变量来评估不同吸烟人群中的遗传关联。所有受试者均为牙科登记处和 DNA 存储库项目的参与者。使用 TaqMan 化学方法对 OPRM1 中的两个标记物（rs553202 和 rs7755635）进行基因分型。使用 PLINK 中实现的逻辑回归分析进行分析。设定的 alpha 值为 5%，每个标记物的 Hardy-Weinberg 平衡通过自由度为 1 的卡方检验进行评估。共纳入 1897 例患者，根据吸烟频率和数量以及精神疾病状况将其分配到八个不同的组中。在 OPRM1 中，两个标记物与吸烟之间没有显著关联。当将精神疾病和牙科临床数据（牙齿缺失、龋齿和牙周炎）用作协变量时，当使用非吸烟者作为对照组时，与重度吸烟有关联。我们没有饮食或微生物组数据来考虑这些牙科分析，并且建议在未来始终将这些数据纳入其中。仅在添加协变量精神疾病和口腔临床数据后，才发现了显著的结果。
