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Approved research

CCL3L1 and CCR5 delta 32 CNV study in extremes of the lung function distribution in smokers

Principal Investigator: Dr Edward Hollox
Approved Research ID: 7140
Approval date: September 1st 2014 | Completion date: June 21st 2019

Lay summary

COPD is a long-term progressive condition affecting ~900,000 people in the UK accounting for ~30,000 deaths and over £500m of NHS costs annually. Copy number variation (CNV) could account for some of the variability in COPD risk and lung function. We aim to study CNV of two genes in relation to COPD and lung function. CCL3L1 encodes a pro-inflammatory cytokine. There is a relationship between CCL3L1 copy number (CN) and protein expression levels, and some evidence that CCL3L1 CN is associated with lung function. CCR5 encodes a receptor for CCL3L1 and contains a polymorphic 32bp deletion. Genetic approaches to understanding the mechanisms underlying COPD aim to discover targets for drug development and unravel disease heterogeneity facilitating stratified approaches to treatment. CCL3L1 and CCR5d32 CN measurements for all UK Biobank particpants included in this project will be returned to UK Biobank to be made available to other researchers. CN at some regions can be inferred from SNP data but complex CN regions (where CN varies from 0 to 6 or more) require custom-designed assays. CCL3L1 CN varies from 1 to 6 and the ?gold standard? approach for measurement is the paralogue ratio test (PRT). CCL3L1 is a ligand for CCR5, a receptor that contains a polymorphic deletion associated with other diseases, including asthma. We will genotype CCL3L1 CN and CCR5d32 in smokers with good or bad lung function and test for association with lung function to clarify the therapeutic opportunities of the CCL3L1-CCR5 axis in COPD. We will genotype 2500 heavy smokers with good lung function and 2500 heavy smokers with poor lung function. These will be selected from the 50,000 individuals for whom DNA has been extracted for the UK BiLEVE consortium.