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.
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.
Authors: Tatsiana Beiko; Michael G Janech; Alexander V Alekseyenko; Carl Atkinson; Harvey O Coxson; Jeremy L Barth; Sarah E Stephenson; Carole L Wilson; Lynn M Schnapp; Alan Barker; Mark Brantly; Robert A Sandhaus; Edwin K Silverman; James K Stoller; Bruce Trapnell; Strange Charlie Journal: Chronic Obstr Pulm Dis Date: 2017-07-15
Authors: Surya P Bhatt; Hrudaya P Nath; Young-Il Kim; Rekha Ramachandran; Jubal R Watts; Nina L J Terry; Sushil Sonavane; Swati P Deshmane; Prescott G Woodruff; Elizabeth C Oelsner; Sandeep Bodduluri; MeiLan K Han; Wassim W Labaki; J Michael Wells; Fernando J Martinez; R Graham Barr; Mark T Dransfield Journal: Respir Res Date: 2018-12-18
Authors: Imran Haq; Sally Chappell; Simon R Johnson; Juzer Lotya; Leslie Daly; Kevin Morgan; Tamar Guetta-Baranes; Josep Roca; Roberto Rabinovich; Ann B Millar; Seamas C Donnelly; Vera Keatings; William MacNee; Jan Stolk; Pieter S Hiemstra; Massimo Miniati; Simonetta Monti; Clare M O'Connor; Noor Kalsheker Journal: BMC Med Genet Date: 2010-01-15 Impact factor: 2.103
Authors: S J Rottier; L C Dreuning; J van Pelt; A A W van Geloven; X D Y Beele; P M Huisman; W Y Deurholt; C A Rottier; K van Leeuwen; M de Boer; G van Mierlo; M A Boermeester; W H Schreurs Journal: Colorectal Dis Date: 2020-09-01 Impact factor: 3.917