A Novel Polymorphism in Secretory Phospholipase A2-IID Is Associated with Body Weight Loss in Chronic Obstructive Pulmonary Disease

Abstract

Chronic and systemic inflammation, a potential cause of body weight loss in patients with chronic obstructive pulmonary disease (COPD), may be associated with the proinflammatory properties of secretory phospholipases A2 (sPLA2s), especially the group II subfamily sPLA2s. We tested our hypothesis that the individual susceptibility to body weight loss in patients with COPD is attributed to the genetic variances of this sPLA2 gene region. A total of 12 single nucleotide polymorphisms (SNPs) encompassing the sPLA2 gene region were determined in 276 male patients with COPD. We first analyzed our patients whose body mass index (BMI) was at the bottom 100 (BMI, 17.13 +/- 1.29 kg/m2) and at the top 100 (23.83 +/- 1.98) in relation to SNPs. Both the Fisher's exact test (odds ratio, 2.36; 95% confidence interval, 1.34-4.18; p = 0.004) and logistic regression analysis (odds ratio, 2.10; 95% confidence interval, 1.13-3.90; p = 0.019) showed statistical significance between one SNP (National Center for Biotechnology Information SNP reference: rs584367) and the reduction of BMI in the recessive model in patients with COPD. Using all the patients, a significant difference between the values of BMI (log transformed) of the mutant group (CT + TT) and that of the nonmutant group (CC) of this SNP (mean [SE], 1.293 [0.005] vs. 1.317 [0.006]; p = 0.003) was found after adjustment for age, smoking habit, and pulmonary function (analysis of covariance). Importantly, this SNP caused a change in amino acids in sPLA2-IID protein (Gly80Ser). These results suggest that sPLA2-IID may be one of the susceptibility genes that contribute to body weight loss in patients with COPD.