Published ahead of print on July 7, 2005, doi:10.1164/rccm.200503-319OC Am. J. Respir. Crit. Care Med., Volume 172, Number 9, November 2005, 1097-1104 A more recent version of this article appeared on November 1, 2005
Submitted on March 1, 2005 A Novel Polymorphism in Secretory Phospholipase A2-IID is Associated with Body Weight Loss in COPDNoriaki Takabatake1,1 First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan, 2 HuBit genomix. Inc., Tokyo, Japan * To whom correspondence should be addressed. E-mail: msata{at}med.id.yamagata-u.ac.jp.
Rationale: Chronic and systemic inflammation, a potential cause of body weight loss in patients with COPD, may be associated with the pro-inflammatory 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 sPLA2s gene region. Methods: A total of twelve SNPs encompassing the sPLA2s gene region were determined in 276 male patients with COPD. Measurements and Main Results: We first analyzed our patients whose BMI are the bottom one hundred [BMI (kg/m2); 17.13 ± 1.29], and are the top one hundred (23.83 ± 1.98) in relation to SNPs. Both of Fisher's exact test [odds ratio (95% CI): 2.36 (1.34 - 4.18), p = 0.004] and logistic regression analysis [2.10 (1.13 - 3.90), p = 0.019] showed statistical significance between one SNP (NCBI SNP reference: rs584367) and the reduction of BMI in the recessive model in patients with COPD. Using the whole patients, a significant difference between the values of BMI (log transformed) of mutant group (CT + TT) and that of non-mutant group (CC) of this SNP [mean (SE): 1.293 (0.005) vs. 1.317 (0.006), p = 0.003] was found after adjustment with age, smoking habit, and pulmonary function (ANCOVA). Importantly, this SNP causes amino acids change 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: SNPs, sPLA2-IID gene, body weight loss, COPD, ANCOVA
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