The role of ALOX5AP, LTA4H and LTB4R polymorphisms in determining baseline lung function and COPD susceptibility in UK smokersReportar como inadecuado




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BMC Medical Genetics

, 12:173

Genetic epidemiology and genetic associations

Abstract

BackgroundWe have previously shown evidence that polymorphisms within genes controlling leukotriene B4 LTB4 production ALOX5AP and LTA4H are associated with asthma susceptibility in children. Evidence also suggests a potential role of LTB4 in COPD disease mechanisms including recruitment of neutrophils to the lung. The aim of the current study was to see if these SNPs and those spanning the receptor genes for LTB4 LTB4R1 and LTB4R2 influence baseline lung function and COPD susceptibility-severity in smokers.

MethodsEight ALOX5AP, six LTA4H and six LTB4R single nucleotide polymorphisms SNPs were genotyped in a UK Smoking Cohort n = 992. Association with baseline lung function FEV1 and FEV1-FVC ratio was determined by linear regression. Logistic regression was used to compare smoking controls n = 176 with spirometry-defined COPD cases n = 599 and to more severe COPD cases GOLD stage 3 and 4, n = 389.

ResultsNo association with ALOX5AP, LTA4H or LTB4R survived correction for multiple testing. However, we showed modest association with LTA4H rs1978331C intron 11 with increased FEV1 p = 0.029 and with increased FEV1-FVC ratio p = 0.020.

ConclusionsThese data suggest that polymorphisms spanning ALOX5AP, LTA4H and the LTB4R locus are not major determinants of baseline lung function in smokers, but provide tentative evidence for LTA4H rs1978331C intron 11 in determining baseline FEV1 and FEV1-FVC ratio in Caucasian Smokers in addition to our previously identified role in asthma susceptibility.

List of Abbreviations5-LO pathway5-lipoxygenase pathway

95% CI95% confidence interval

ALOX55-lipoxygenase

ALOX5AP5-lipoxygenase activating protein

COPDChronic obstructive pulmonary disease

CysLTCysteinyl leukotriene

CYSLTR1Cysteinyl leukotriene receptor 1

FEV1Forced expiratory volume in one second: FEV1-FVC: Ratio of FEV1 to FVC

FEV1-FVCRatio of FEV1 to FVC

FLAP5-lipoxygenase activating protein

FVCForced vital capacity

GOLDGlobal Initiative for Obstructive Lung Diseases

LDLinkage disequilibrium

LTA4B4, C4, D4, E4: Leukotriene A4, B4, C4, D4, E4

LTA4HLeukotriene A4 hydrolase

LTB4R1-2Leukotriene B4 receptor 1-2

LTC4SLeukotriene C4 synthase

MAFMinor allele frequency

MIMyocardial infarction

OROdds ratio

PGPProline-glycine-proline

PostBDPost bronchodilator

SNPSingle nucleotide polymorphism

TBTuberculosis

UKUnited Kingdom

UTRUntranslated region.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-12-173 contains supplementary material, which is available to authorized users.

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Autor: Asif S Tulah - Stuart G Parker - Miriam F Moffatt - Andrew J Wardlaw - Martin J Connolly - Ian Sayers

Fuente: https://link.springer.com/







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