Matrix metalloprotease polymorphisms are associated with gas transfer in alpha 1 antitrypsin deficiency.

Abstract:

UNLABELLED:Alpha-1-antitrypsin deficiency [AATD] is associated with variable development of emphysema and other features of chronic obstructive pulmonary disease [COPD]. Matrix metalloproteinases [MMPs] are believed to be important in the pathophysiology of COPD, and may therefore confer susceptibility to this phenotype in patients with AATD. OBJECTIVES:to assess the role of polymorphism of MMP1, MMP3 and MMP12 in AATD phenotypes. METHODS:424 PiZZ subjects from the UK AATD Registry were assessed for history of chronic bronchitis [CB], post-bronchodilator lung function impairment and decline of lung function. Tag single nucleotide polymorphisms (SNPs) for MMP1, MMP3 and MMP12 were chosen using HapMap [r(2)>0.8, MAF>0.05] and were genotyped using TaqMan genotyping technologies. Quantitative genetic association was assessed using regression modelling to correct for covariates. RESULTS:in patients with AATD, carriers of the G allele of rs678815 [MMP3] had lower gas transfer [KCO] [P = 0.025, B =-7.766] than the homozygous wild type, while carriers of the T allele of rs470358 [MMP1] had higher KCO [P = 0.025, B = 6.130]. CONCLUSIONS:variations in MMP1 and MMP3 are associated with gas transfer in AATD, supporting a previous family study showing linkage of KCO to this gene region. Replication of these preliminary data is now required particularly if MMP inhibitors are to be considered as a therapeutic option.

journal_name

Ther Adv Respir Dis

authors

McAloon CJ,Wood AM,Gough SC,Stockley RA

doi

10.1177/1753465809102263

subject

Has Abstract

pub_date

2009-02-01 00:00:00

pages

23-30

issue

1

eissn

1753-4658

issn

1753-4666

pii

3/1/23

journal_volume

3

pub_type

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