<it>SERPINE2 </it>haplotype as a risk factor for panlobular type of emphysema

• Main Authors: Kukkonen Mari K (Author), Tiili Emmi (Author), Hämäläinen Satu (Author), Vehmas Tapio (Author), Oksa Panu (Author), Piirilä Päivi (Author), Hirvonen Ari (Author)
• Format: Book
• Published: BMC, 2011-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1186/1471-2350-12-157; 1471-2350
• Keywords: Internal medicine; RC31-1245; Genetics; QH426-470
• Source: BMC Medical Genetics, Vol 12, Iss 1, p 157 (2011)

<p>Abstract</p> <p>Background</p> <p><it>SERPINE2 </it>(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 <it>SERPINE2 </it>polymorphisms in the development of pulmonary emphysema and different emphysema subtypes.</p> <p>Methods</p> <p>Four single nucleotide polymorphisms (SNPs) in <it>SERPINE2 </it>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 (DL_CO), and specific diffusing capacity (DL_CO/VA).</p> <p>Results</p> <p>Three of the studied <it>SERPINE2 </it>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 (<it>p </it>= 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.</p> <p>Conclusions</p> <p>Our results support the previously found association between <it>SERPINE2 </it>polymorphisms and pulmonary emphysema. As a novel finding, our study suggests that the <it>SERPINE2 </it>gene may in particular be involved in the development of panlobular changes, <it>i.e.</it>, the same type of changes that are involved in alpha-1-antitrypsin (AAT) -deficiency.</p>