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

First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata; and HuBit Genomix, Inc., Tokyo, Japan

Correspondence and requests for reprints should be addressed to Makoto Sata, M.D., First Department of Internal Medicine, Yamagata University School of Medicine, 2-2-2, Iida-Nishi, Yamagata 990-9585, Japan. E-mail address: msata{at}med.id.yamagata-u.ac.jp

Rationale: 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.

Objectives: 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.

Methods: A total of 12 single nucleotide polymorphisms (SNPs) encompassing the sPLA₂ gene region were determined in 276 male patients with COPD.

Measurements and Main Results: 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).

Conclusions: These results suggest that sPLA₂-IID may be one of the susceptibility genes that contribute to body weight loss in patients with COPD.

Key Words: analysis of covariance • body weight loss • chronic obstructive pulmonary disease • single nucleotide polymorphism • sPLA₂-IID gene

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