Leptin Receptor Polymorphisms and Lung Function Decline in Chronic Obstructive Pulmonary Disease

¹ Dept of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD
² Inherited Disease Research Branch, National Human Genome Research Institute (NHGRI), National Institutes of Health
³ Dept of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD
⁴ Division of Biostatistics, School of Public Health, University of Minnesota, St. Paul, Minnesota
⁵ Dept of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD; and Dept of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD

^* To whom correspondence should be addressed. E-mail: kbarnes{at}jhmi.edu.

	Abstract

Only a fraction of all smokers develop 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. This study examined the association between genetic variants in the LEPR gene and lung function decline in COPD.

429 European Americans were randomly selected from the NHLBI Lung Health Study. Thirty-six single nucleotide polymorphisms (SNPs) in LEPR were genotyped using the Illumina^TM platform. Mean annual decline in FEV₁ % predicted over the five-year 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.