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Leptin receptor polymorphisms and lung function decline in COPD

¹ Dept of Medicine, School of Medicine, Johns Hopkins University, ³ Dept of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, ² Inherited Disease Research Branch, National Human Genome Research Institute (NHGRI), National Institutes of Health, Baltimore, MD, and ⁴ Division of Biostatistics, School of Public Health, University of Minnesota, St. Paul, MN, USA.

CORRESPONDENCE: K. C. Barnes, The Johns Hopkins Asthma & Allergy Center, 5501 Hopkins Bayview Circle, Room 3A.62, Baltimore, MD 21224, USA. E-mail: kbarnes{at}jhmi.edu

Keywords: Chronic obstructive pulmonary disease, leptin receptor, lung function decline, polymorphisms

Received: August 5, 2008
Accepted December 19, 2008

Only a fraction of all smokers develop chronic obstructive pulmonary disease (COPD), suggesting a large role for genetic susceptibility. The leptin receptor (LEPR) is present in human lung tissue and may play a role in COPD pathogenesis. The present study examined the association between genetic variants in the LEPR gene and lung function decline in COPD.

In total, 429 European Americans were randomly selected from the National Heart Lung and Blood Institute Lung Health Study. 36 single nucleotide polymorphisms (SNPs) in LEPR were genotyped using the Illumina^TM GoldenGate platform (Broad Institute, Cambridge, MA, USA). Mean annual decline in forced expiratory volume in 1 s % predicted over the 5-yr period was calculated using linear regression. Linear regression models were also used to adjust for potential confounders. In addition, in vivo expression of the receptor gene was assessed with immunohistochemistry on lungs from smoke-exposed inbred mice.

We identified significant associations (p<0.05) between lung function decline and 21 SNPs. Haplotype analyses confirmed several of these associations seen with individual markers. Immunohistochemistry results in inbred mice strains support a potential role of LEPR in COPD pathogenesis.

We identified genetic variants in the LEPR gene significantly associated with lung function decline in a population of smokers with COPD. Our results support a role for LEPR as a novel candidate gene for COPD.