Finnish Institute of Occupational Health, Helsinki, Finland.
BMC Med Genet. 2011 Dec 7;12:157. doi: 10.1186/1471-2350-12-157.
SERPINE2 (serpin peptidase inhibitor, clade E, member 2) has previously been identified as a positional candidate gene for chronic obstructive pulmonary disease (COPD) and has subsequently been associated to COPD and emphysema in several populations. We aimed to further examine the role of SERPINE2 polymorphisms in the development of pulmonary emphysema and different emphysema subtypes.
Four single nucleotide polymorphisms (SNPs) in SERPINE2 were analyzed from 951 clinically and radiologically examined Finnish construction workers. The genotype and haplotype data was compared to different emphysematous signs confirmed with high-resolution computed tomography (HRCT), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), diffusing capacity (DLCO), and specific diffusing capacity (DLCO/VA).
Three of the studied SERPINE2 SNPs (rs729631, rs975278, and rs6748795) were found to be in tight linkage disequilibrium. Therefore, only one of these SNPs (rs729631) was included in the subsequent analyses, in addition to the rs840088 SNP which was in moderate linkage with the other three studied SNPs. The rs729631 SNP showed a significant association with panlobular emphysema (p = 0.003). In further analysis, the variant allele of the rs729631 SNP was found to pose over two-fold risk (OR 2.22, 95% CI 1.05-4.72) for overall panlobular changes and over four-fold risk (OR 4.37, 95% CI 1.61-11.86) for pathological panlobular changes. A haplotype consisting of variant alleles of both rs729631 and rs840088 SNPs was found to pose an almost four-fold risk for overall panlobular (OR 3.72, 95% CI 1.56-8.90) and subnormal (OR 3.98, 95% CI 1.55-10.20) emphysema.
Our results support the previously found association between SERPINE2 polymorphisms and pulmonary emphysema. As a novel finding, our study suggests that the SERPINE2 gene may in particular be involved in the development of panlobular changes, i.e., the same type of changes that are involved in alpha-1-antitrypsin (AAT) -deficiency.
丝氨酸蛋白酶抑制剂，E 族，成员 2（SERPINE2）先前被鉴定为慢性阻塞性肺疾病（COPD）的候选基因，随后在多个群体中与 COPD 和肺气肿相关。我们旨在进一步研究 SERPINE2 多态性在肺肺气肿和不同肺气肿亚型发展中的作用。
从 951 名经临床和放射学检查的芬兰建筑工人中分析了 SERPINE2 的 4 个单核苷酸多态性（SNP）。将基因型和单倍型数据与通过高分辨率计算机断层扫描（HRCT）、用力肺活量（FVC）、一秒用力呼气量（FEV1）、弥散量（DLCO）和特定弥散量（DLCO/VA）确认的不同肺气肿迹象进行比较。
研究的 SERPINE2 中的 3 个 SNP（rs729631、rs975278 和 rs6748795）被发现紧密连锁不平衡。因此，除了与其他三个研究的 SNP 中度连锁的 rs840088 SNP 外，仅对其中一个 SNP（rs729631）进行了后续分析。rs729631 SNP 与全小叶肺气肿呈显著相关性（p = 0.003）。在进一步分析中，发现 rs729631 SNP 的变异等位基因使全小叶改变的总体风险增加两倍以上（OR 2.22，95%CI 1.05-4.72），并且使病理性全小叶改变的风险增加四倍以上（OR 4.37，95%CI 1.61-11.86）。发现由 rs729631 和 rs840088 SNP 的变异等位基因组成的单倍型使全小叶（OR 3.72，95%CI 1.56-8.90）和亚正常（OR 3.98，95%CI 1.55-10.20）肺气肿的风险几乎增加四倍。
我们的结果支持先前发现的 SERPINE2 多态性与肺肺气肿之间的关联。作为一项新发现，我们的研究表明，SERPINE2 基因可能特别参与全小叶改变的发展，即涉及α-1-抗胰蛋白酶（AAT）缺陷的相同类型的改变。
