C4BQ synergizes with smoking to precipitate chronic obstructive pulmonary disease

Abstract

Background: We previously demonstrated that C4B*Q0 is inconsistent with health for smokers (Arason et al., 2007). The carrier frequency of C4B*Q0 drops from 19.2% through 4% to 0% in healthy Icelandic smokers at ages 50 and 60, respectively. In search for a reason, we analyzed individuals with suspected cardiovascular disease (CVD), and found that C4B*Q0 was markedly raised in smokers with their first lifetime myocardial infarction (MI) (p = 0.0003, odds ratio (OR) 22.66) and also in smokers with angina pectoris (AP) (p = 0.005, OR 30.07). Moreover, smokers with C4B*Q0 had a markedly decreased chance for survival after MI (hazard ratio 3.50, p = 0.008) (Blaskó et al., 2008). Rationale: C4B*Q0 is inconsistent with health for smokers and this may be due to their high risk of developing CVD. However, other diseases affecting the middle aged should also be studied. Methods: We analyzed C4B*Q0 carrier frequencies in a population sample of 412 Icelanders, using high-voltage agarose electrophoresis (HVAGE). Patients with CVD were excluded from the study. The results were correlated with smoking status and with diagnosis of chronic obstructive pulmonary disease (COPD) stage II. Results: Carrier frequencies of C4B*Q0 dropped from 20.7% to 14.42% after age 50 (p = 0.067) and when the analysis was confined to smokers, the frequencies dropped from 17.2% to 9.6% (p = 0.109). The frequencies were raised in middle-aged patients with COPD stage II (p = 0.018) and highly increased in smokers (p = 0.007). Conclusions: C4B*Q0 synergizes with smoking to precipitate COPD. C4B*Q0 thus synergizes with smoking in precipitating two important diseases affecting the middle-aged, CVD and COPD. Previous results showing a drop in C4B*Q0 in healthy smokers at middle age received moderate support; the results were not significant but interesting, and may benefit from increasing the sample size.