A novel polymorphism in secretory phospholipase A2-IID is associated with body weight loss in chronic obstructive pulmonary disease
A novel polymorphism in secretory phospholipase A2-IID is associated with body weight loss in chronic obstructive pulmonary disease
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DOI：
10.1164/rccm.200503-319oc
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发表时间：
2005-11-01
影响因子：
24.7
通讯作者：
Kubota, I
中科院分区：
文献类型：
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作者：
Takabatake, N;Sata, M;Kubota, I
理由：慢性和全身性炎症是慢性阻塞性肺病 (COPD) 患者体重减轻的潜在原因，可能与分泌性磷脂酶 A(2) (sPLA(2)s) 的促炎特性有关，尤其是 II 组亚家族 sPLA2s。 目的：我们检验了我们的假设，即个体对体重的易感性：COPD 患者的体重减轻归因于遗传因素。 方法：在 276 名患有 COPD 的男性患者中测定了总共 12 个包含 sPLA(2) 基因区域的单核苷酸多态性 (SNP)。测量和主要结果：我们首先分析了体重指数 (BMI) 处于最低 100 的患者（BMI，17.13 +/- 1.29 kg/m(2)）和 与 SNP 相关的前 100 位 (23.83 +/- 1.98)。 Fisher 精确检验（比值比，2.36；95% 置信区间，1.34-4.18；p = 0.004）和逻辑回归分析（比值比，2.10；95% 置信区间，1.13-3.90；p = 0.019）均显示出一个 SNP（国家生物技术信息中心 SNP 参考号：rs584367）和BMI 的降低 COPD 患者的隐性模型。使用所有患者，在调整年龄、吸烟习惯和肺功能（协方差分析）后，发现该 SNP 突变组 (CT + TT) 和非突变组 (CC) 的 BMI（对数转换）值之间存在显着差异（平均值 [SE]，1.293 [0.005] 与 1.317 [0.006]；p = 0.003）。重要的是，该 SNP 导致 sPLA(2)-IID 蛋白 (Gly80Ser) 中的氨基酸发生变化。结论：这些结果表明 sPLA(2)-IID 可能是导致 COPD 患者体重减轻的易感基因之一。
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 A(2) (sPLA(2)s), 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 sPLA(2) gene region.Methods: A total of 12 single nucleotide polymorphisms (SNPs) encompassing the sPLA(2) 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/m(2)) 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 sPLA(2)-IID protein (Gly80Ser).Conclusions: These results suggest that sPLA(2)-IID may be one of the susceptibility genes that contribute to body weight loss in patients with COPD.