Association of serotonin transporter gene variation with smoking, chronic obstructive pulmonary disease, and its depressive symptoms

Abstract

A serotonin transporter gene, SLC6A4, is thought to be related to nicotine dependence and depression, one of the comorbidities of chronic obstructive pulmonary disease (COPD). To investigate the association between SLC6A4 variation and tobacco consumption, susceptibility to COPD, and depression status. In all, 247 patients with COPD and 119 control subjects were genotyped for 5 tag single-nucleotide polymorphisms (SNPs) of SLC6A4. We analyzed the correlation between these genotypes and COPD, using the results of a pulmonary function test or chest computed tomography; data on tobacco consumption (packyears); and the depression score based on the hospital anxiety and depression scale (HADS) after adjusting for age, gender, and smoking status (and pack-years, when appropriate). The rare allele rs2020936 was significantly associated with COPD incidence in the trend model (P¼0.003; odds ratio, 2.20; 95% confidence interval, 1.31-3.74). This allele was also associated with the number of pack-years (P¼0.026). The major allele of another SNP of SLC6A4, namely rs3794808, correlated with the HADS depression score (P¼0.016). We conclude that SLC6A4 variation affects COPD pathogenesis, and this effect depends partly on tobacco consumption. SLC6A4 variation also affects depressive symptoms. SLC6A4 could be modified to prevent COPD and treat the depressive symptoms of COPD.

Genetics of smoking and depression

“…In a study of 185 current smokers, Lerman et al (2000) observed a positive association between neuroticism and smoking behaviors in individuals with S expression of the 5-HTTLPR region, but not those with the L genotype. These findings were supported by Ishii et al (2011), who found that 5-HTTLPR S genotype expression was associated with 247 patients with chronic obstructive pulmonary disease (COPD). These results are encouraging, though there are also conflicting results.…”

“…Positive findings in both association (e.g., Audrain-McGovern et al 2004: Ishii et al 2011Stapleton et al 2011) and genetic linkage (Pergadia et al 2011) studies, however, are providing a promising foundation for future investigations.…”

Serotonin and Corticosterone Rhythms in Mice Exposed to Cigarette Smoke and in Patients with COPD: Implication for COPD-Associated Neuropathogenesis

“…The impacts of CS exposure on nocturnal activity are particularly profound and suggest the development of a “depression-like” behavioral pattern in these mice [39]. It has been shown that altered rhythms of plasma 5HT, CORT, and cortisol levels and genetic polymorphisms of the clock genes and 5HT-receptors are directly associated with depression, sleep disorders and decreased locomotor activity [23], [38], [46], [49], [61], [62]. Moreover, it has been reported that plasma levels of 5HT and CORT are elevated by CS exposure in mice [63], [64], presumably due to increased systemic oxidative and carbonyl stress [65].…”

Biomarkers: Symptoms, Survivorship, and Quality of Life

“…The genetic basis for fatigue, 6,58-60 pain, 18,19,61-64 depression, 11,12,65-67 and sleep disturbance 7-9,68 in patients with cancer and other chronic medical condition has been the subject of a number of recent reviews. Again, many of the genetic studies of these symptoms in cancer patients have focused on an evaluation of candidate genes associated with pro- and anti-inflammatory cytokines.…”