Copy number variation of the Beta-defensin genes in europeans: no supporting evidence for association with lung function, chronic obstructive pulmonary disease or asthma

Wain, Louise V.; Odenthal-Hesse, Linda; Abujaber, Razan; Sayers, Ian; Beardsmore, Caroline; Gaillard, Erol A.; Chappell, Sally; Dogaru, Cristian M.; McKeever, Tricia; Guetta-Baranes, Tamar; Kalsheker, Noor; Kuehni, Claudia E.; Hall, Ian P.; Tobin, Martin D.; Hollox, Edward J. (2014). Copy number variation of the Beta-defensin genes in europeans: no supporting evidence for association with lung function, chronic obstructive pulmonary disease or asthma. PLoS ONE, 9(1), e84192. Public Library of Science 10.1371/journal.pone.0084192

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Lung function measures are heritable, predict mortality and are relevant in diagnosis of chronic obstructive pulmonary disease (COPD). COPD and asthma are diseases of the airways with major public health impacts and each have a heritable component. Genome-wide association studies of SNPs have revealed novel genetic associations with both diseases but only account for a small proportion of the heritability. Complex copy number variation may account for some of the missing heritability. A well-characterised genomic region of complex copy number variation contains beta-defensin genes (DEFB103, DEFB104 and DEFB4), which have a role in the innate immune response. Previous studies have implicated these and related genes as being associated with asthma or COPD. We hypothesised that copy number variation of these genes may play a role in lung function in the general population and in COPD and asthma risk. We undertook copy number typing of this locus in 1149 adult and 689 children using a paralogue ratio test and investigated association with COPD, asthma and lung function. Replication of findings was assessed in a larger independent sample of COPD cases and smoking controls. We found evidence for an association of beta-defensin copy number with COPD in the adult cohort (OR = 1.4, 95%CI:1.02-1.92, P = 0.039) but this finding, and findings from a previous study, were not replicated in a larger follow-up sample(OR = 0.89, 95%CI:0.72-1.07, P = 0.217). No robust evidence of association with asthma in children was observed. We found no evidence for association between beta-defensin copy number and lung function in the general populations. Our findings suggest that previous reports of association of beta-defensin copy number with COPD should be viewed with caution. Suboptimal measurement of copy number can lead to spurious associations. Further beta-defensin copy number measurement in larger sample sizes of COPD cases and children with asthma are needed.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine

UniBE Contributor:

Dogaru, Cristian and Kühni, Claudia

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Doris Kopp Heim

Date Deposited:

12 Feb 2014 16:08

Last Modified:

08 Sep 2017 17:18

Publisher DOI:

10.1371/journal.pone.0084192

PubMed ID:

24404154

BORIS DOI:

10.7892/boris.40721

URI:

https://boris.unibe.ch/id/eprint/40721

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