Microsatellite DNA instability in COPD

Study objectives: Cigarette smoking is the prime cause of COPD; however, on ly a few smokers develop the disease, In a previous study, we demonstrated that microsatellite DNA instability (MSI) is a detectable phenomenon in spu tum cells of COPD patients. Therefore, we hypothesize that this genetic alt eration may indicate susceptibility to COPD. Design: In order to investigate this hypothesis, ne compared smokers who de veloped COPD with smokers who did not develop COPD (referred to as non-COPD smokers). Setting: Seven highly polymorphic microsatellite markers were targeted on t he DNA of sputum cells and of WBCs. Patients and participants: We studied 60 non-COPD smokers and 59 severe COP D patients with a similar smoking history (mean +/- SD) of 48 +/- 25 and 54 +/- 33 pack-years, respectively (p = 0.77). Non-COPD smokers were tested o nce; COPD smokers were tested twice, with an interval of 24 months between tests. Results: MSI was detected in 14 COPD patients (24%) but in none of the non- COPD smokers. In 10 COPD patients, MSI was exhibited by one microsatellite marker; in the remaining 4 COPD patients, MSI was exhibited by two differen t alleles. The most commonly affected marker was THRA1 on chromosome 17 (43 %). No significant differences were found between MSI-positive and MSI-nega tive COPD patients for clinical or laboratory; parameters, survival, and de velopment of lung cancer. No change in the microsatellite alleles was found between the tests performed with a 24-month interval. Conclusions: This study demonstrated that MSI was found exclusively in the sputum cells of smokers with COPD, The results support the hypothesis that MSI could be part of the complex genetic basis of COPD, and it could be a m arker of die genetic alteration caused by smoking that allows COPD to devel op.