Genetic Polymorphisms of Surfactant Protein D rs2243639, Interleukin (IL)-1β rs16944 and IL-1RN rs2234663 in Chronic Obstructive Pulmonary Disease, Healthy Smokers, and Non-Smokers

Background and Objectives Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease that involves the activity of various inflammatory cells and mediators. It has been suggested that susceptibility to COPD is, at least in part, genetically determined. The primary aim of...

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Bibliographic Details
Published in:Molecular diagnosis & therapy 2014-06, Vol.18 (3), p.343-354
Main Authors: Issac, Marianne Samir M., Ashur, Wafaa, Mousa, Heba
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Cancer Research
Human Genetics
Laboratory Medicine
Molecular Medicine
Original Research Article
Pharmacotherapy
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Summary:Background and Objectives Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease that involves the activity of various inflammatory cells and mediators. It has been suggested that susceptibility to COPD is, at least in part, genetically determined. The primary aim of this study was to investigate the association between surfactant protein D ( SFTPD ) rs2243639, interleukin ( IL )- 1β rs16944 and IL-1 receptor antagonist ( IL-1RN ) rs2234663 gene polymorphisms and COPD susceptibility, as well as examining the association between the various IL-1RN/IL-1β haplotypes and pulmonary function tests (PFT). Secondly, we aimed to examine the influence of SFTPD rs2243639 polymorphism on serum surfactant protein D (SP-D) level. Methods A total of 114 subjects were recruited in this study and divided into three groups: 63 COPD patients, 25 asymptomatic smokers, and 26 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed for the detection of SFTPD rs2243639 and IL-1β rs16944 polymorphisms. Detection of variable numbers of an 86-bp tandem repeat (VNTR) of IL-1RN was done using PCR. Serum SP-D level was measured using enzyme linked-immunosorbent assay. PFTs were measured by spirometry. Results Carriers of the SFTPD AG and AA polymorphic genotypes constituted 71.4 % of COPD patients versus 48 % in asymptomatic smokers, with a statistically significant difference between the two groups ( p  = 0.049). Smokers who were carriers of the polymorphic SFTPD rs2243639 A allele (AG and AA genotypes) have a 2.708 times risk of developing COPD when compared with wild-type GG genotype carriers [odds ratio (OR) 2.708 (95 % CI 1.041–7.047)]. Forced expiratory flow (FEF) 25–75 % predicted was higher in IL-1RN *1/*1 when compared with *1/*2 ( p  = 0.013). FEF25–75 % predicted in carriers of haplotype IL-1RN *1 / IL-1β T (49.21 ± 10.26) was statistically significantly higher than in carriers of IL-1RN *2/IL-1β T (39.67 ± 12.64) [ p  = 0.005]. Forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) in carriers of haplotype IL-1RN *1 / IL-1β T (64.09 ± 6.39) was statistically significantly higher than in carriers of IL-1RN *2 / IL-1βT (59.44 ± 7.71) [ p  = 0.048]. There was no association between SFTPD rs2243639 genotypes and serum SP-D level. Conclusions Smokers who are carriers of the SFTPD AG and AA polymorphic genotypes may be at a higher risk of developing COPD when compared with wild-type
ISSN:1177-1062
1179-2000
DOI:10.1007/s40291-014-0084-5