SERPINE2 haplotype as a risk factor for panlobular type of emphysema.
SERPINE2 haplotype as a risk factor for panlobular type of emphysema.
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DOI：
10.1186/1471-2350-12-157
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发表时间：
2011-12-07
影响因子：
--
通讯作者：
Hirvonen A
中科院分区：
文献类型：
--
作者：
Kukkonen MK;Tiili E;Hämäläinen S;Vehmas T;Oksa P;Piirilä P;Hirvonen A
SERPINE 2（丝氨酸蛋白酶抑制剂，进化枝E，成员2）先前已被鉴定为慢性阻塞性肺疾病（COPD）的位置候选基因，并且随后在几个群体中与COPD和肺气肿相关。我们的目的是进一步研究SERPINE 2多态性在肺气肿和不同肺气肿亚型的发展中的作用。从951名临床和放射学检查的芬兰建筑工人中分析了SERPINE 2的四个单核苷酸多态性（SNPs）。将基因型和单倍型数据与经高分辨率计算机断层扫描（HRCT）、用力肺活量（FVC）、第一秒用力呼气量（FEV 1）、弥散量（DLCO）和比弥散量（DLCO/VA）证实的不同肺气肿体征进行比较。三个研究SERPINE 2 SNP（rs729631，rs 975278和rs6748795）被发现处于紧密连锁不平衡。因此，除了与其他三个研究的SNP中度连锁的rs 840088 SNP之外，这些SNP中只有一个（rs729631）被包括在随后的分析中。rs729631 SNP显示与全小叶性肺气肿显著相关（p = 0.003）。在进一步的分析中，发现rs729631 SNP的变异等位基因对整体全小叶变化造成超过2倍的风险（OR 2.22，95% CI 1.05-4.72），对病理性全小叶变化造成超过4倍的风险（OR 4.37，95% CI 1.61-11.86）。由rs729631和rs 840088 SNP的变异等位基因组成的单倍型被发现对整体全小叶（OR 3.72，95%CI 1.56-8.90）和亚正常（OR 3.98，95%CI 1.55-10.20）肺气肿造成几乎四倍的风险。我们的研究结果支持先前发现的SERPINE 2多态性与肺气肿之间的关联。作为一个新的发现，我们的研究表明SERPINE 2基因可能特别参与了全小叶变化的发展，即，与α-1-抗胰蛋白酶（AAT）缺乏有关的相同类型的变化。
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.
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DOI：
10.1097/00001648-199001000-00010
发表时间：
1990-01-01
期刊：
Epidemiology (Cambridge, Mass.)
影响因子：
--
作者：
Rothman, K J
通讯作者：
Rothman, K J
影响因子：
3
作者：
Huuskonen, O;Kivisaari, L;Vehmas, T
通讯作者：
Vehmas, T
影响因子：
--
作者：
Zhong L;Fu WP;Sun C;Dai LM;Zhang YP
通讯作者：
Zhang YP
影响因子：
--
作者：
Fujimoto K;Ikeda S;Arai T;Tanaka N;Kumasaka T;Ishii T;Kida K;Muramatsu M;Sawabe M
通讯作者：
Sawabe M
影响因子：
3.3
作者：
Tomashefski, JF;Crystal, RG;Stoller, JK
通讯作者：
Stoller, JK