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Polymorphism of SERPINE2 gene is associated with pulmonary emphysema in consecutive autopsy cases.

ABSTRACT: BACKGROUND: The SERPINA1, SERPINA3, and SERPINE2 genes, which encode antiproteases, have been proposed to be susceptible genes for of chronic obstructive pulmonary disease (COPD) and related phenotypes. Whether they are associated with emphysema is not known. METHODS: Twelve previously reported single nucleotide polymorphisms (SNPs) in SERPINA1 (rs8004738, rs17751769, rs709932, rs11832, rs1303, rs28929474, and rs17580), SERPINA3 (rs4934, rs17473, and rs1800463), and SERPINE2 (rs840088 and rs975278) were genotyped in samples obtained from 1,335 consecutive autopsies of elderly Japanese people. The association between these SNPs and the severity of emphysema, as assessed using macroscopic scores, was determined. RESULTS: Emphysema of more than moderate degree was detected in 189 subjects (14.1%) and showed a significant gender difference (males, 20.5% and females, 7.0%; p < 0.0001). Among the 12 examined SNPs, only rs975278 in the SERPINE2 gene was positively associated with emphysema. Unlike the major alleles, homozygous minor alleles of rs975278 were associated with emphysema (odds ratio (OR) = 1.54; 95% confidence interval (CI) = 1.02-2.30; p = 0.037) and the association was very prominent in smokers (OR = 2.02; 95% CI = 1.29-3.15; p = 0.002). CONCLUSIONS: SERPINE2 may be a risk factor for the development of emphysema and its association with emphysema may be stronger in smokers.

SUBMITTER: Fujimoto K

PROVIDER: S-EPMC2994839 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Polymorphism of SERPINE2 gene is associated with pulmonary emphysema in consecutive autopsy cases.

Fujimoto Koichi K Ikeda Shinobu S Arai Tomio T Tanaka Noriko N Kumasaka Toshio T Ishii Takeo T Kida Kozui K Muramatsu Masaaki M Sawabe Motoji M

BMC medical genetics 20101110

<h4>Background</h4>The SERPINA1, SERPINA3, and SERPINE2 genes, which encode antiproteases, have been proposed to be susceptible genes for of chronic obstructive pulmonary disease (COPD) and related phenotypes. Whether they are associated with emphysema is not known.<h4>Methods</h4>Twelve previously reported single nucleotide polymorphisms (SNPs) in SERPINA1 (rs8004738, rs17751769, rs709932, rs11832, rs1303, rs28929474, and rs17580), SERPINA3 (rs4934, rs17473, and rs1800463), and SERPINE2 (rs8400 ...[more]

PMID: 21067581

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Project description:BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Project description:BACKGROUND:Pulmonary embolism (PE) is associated to high mortality rate worldwide. However, the diagnosis of PE often results inaccurate. Many cases of PE are incorrectly diagnosed or missed and they are often associated to sudden unexpected death (SUD). In forensic practice, it is important to establish the time of thrombus formation in order to determine the precise moment of death. The autopsy remains the gold standard method for the identification of death cause allowing the determination of discrepancies between clinical and autopsy diagnoses. The aim of our study was to verify the morphological and histological criteria of fatal cases of PE and evaluate the dating of thrombus formation considering 5 ranges of time. METHODS:Pulmonary vessels sections were collected from January 2010 to December 2017. Sections of thrombus sampling were stained with hematoxylin and eosin. The content of infiltrated cells, fibroblasts and collagen fibers were scored using a semi-quantitative three-point scale of range values. RESULTS:The 30 autopsies included 19 males (63.3%) and 11 females (36.7%) with an average age of 64.5?±?12.3?years. The time intervals were as follows: early (?1?h), recent (>?1?h to 24?h), recent-medium (>?24?h to 48?h), medium (>?48?h to 72?h) and old (>?72?h). In the first hour, we histologically observed the presence of platelet aggregation by immunofluorescence method for factor VIII and fibrinogen. The presence of lymphocytes has been identified from recent thrombus (>?1?h to 24?h) and the fibroblast cells were peripherally located in vascular tissue between 48 and 72?h, whereas they resulted central and copious after 72?h. CONCLUSIONS:After a macroscopic observation and a good sampling traditional histology, it is important to identify the time of thrombus formation. We identified histologically a range of time in the physiopathology of the thrombus (early, recent, recent-medium, medium, old), allowing to determine the dating of thrombus formation and the exact time of death. CLINICAL TRIAL NUMBER:NCT03887819. TRIAL REGISTRATION:The trial registry is Cliniclatrials.gov, with the unique identifying number NCT03887819. The date of registration was 03/23/2019 and it was "Retrospectively registered".

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Polymorphism of SERPINE2 gene is associated with pulmonary emphysema in consecutive autopsy cases.

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Polymorphism of SERPINE2 gene is associated with pulmonary emphysema in consecutive autopsy cases.

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