SERPINE2 haplotype as a risk factor for panlobular type of emphysemaReport as inadecuate




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BMC Medical Genetics

, 12:157

Genetic epidemiology and genetic associations

Abstract

BackgroundSERPINE2 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.

MethodsFour 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.

ResultsThree 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.

ConclusionsOur 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.

List of AbbreviationsAATalpha-1-antitrypsin

ASBEstudy cohort of asbestos exposed workers recruited in 1996-1997

ASSEstudy cohort of asbestos exposed workers recruited in 2003-2004

COPDchronic obstructive pulmonary disease

DLCOsingle breath diffusing capacity for carbon monoxide, % of predicted

DLCO-VAspecific diffusing capacity, % of predicted

FEV1forced expiratory volume in 1 second, % of predicted

FVCforced vital capacity, % of predicted

HRCThigh resolution computed tomography

HWEHardy-Weinberg equilibrium

LDLinkage disequilibrium

MMPmatrix metalloproteinase

PYpack-years

SERPINA1serpin peptidase inhibitor, clade A, member 1

SERPINE2serpin peptidase inhibitor, clade E, member 2

SNPsingle nucleotide polymorphism.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-12-157 contains supplementary material, which is available to authorized users.

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Author: Mari K Kukkonen - Emmi Tiili - Satu Hämäläinen - Tapio Vehmas - Panu Oksa - Päivi Piirilä - Ari Hirvonen

Source: https://link.springer.com/







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