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Leptin receptor polymorphisms and lung function decline in COPD.

ABSTRACT: 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 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.

SUBMITTER: Hansel NN

PROVIDER: S-EPMC5516636 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Leptin receptor polymorphisms and lung function decline in COPD.

Hansel N N NN Gao L L Rafaels N M NM Mathias R A RA Neptune E R ER Tankersley C C Grant A V AV Connett J J Beaty T H TH Wise R A RA Barnes K C KC

The European respiratory journal 20090205 1

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 nucleoti ...[more]

PMID: 19196818

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Project description:BackgroundBoth allergen-specific IgE and total IgE in serum play a major role in asthma. However, the role of IgE in chronic obstructive pulmonary disease (COPD) is poorly understood. It was the aim of this study to systematically analyze the relationship between serum IgE levels and disease characteristics in large COPD cohorts.MethodsCOSYCONET is a comprehensively characterized cohort of patients with COPD: total IgE and IgE specific to common aeroallergens were measured in serum of 2280 patients, and related to clinical characteristics of the patients. WISDOM is another large COPD population (2477 patients): this database contains the information whether total IgE in serum was elevated (≥ 100 IU/l) or normal in patients with COPD.ResultsBoth in COSYCONET and WISDOM, total IgE was elevated (≥ 100 IU/l) in > 30% of the patients, higher in men than in women, and higher in currently than in not currently smoking men. In COSYCONET, total IgE was elevated in patients with a history of asthma and/or allergies. Men with at least one exacerbation in the last 12 months (50.6% of all men in COSYCONET) had higher median total IgE (71.3 IU/l) than men without exacerbations (48.3 IU/l): this difference was also observed in the subgroups of not currently smoking men and of men without a history of asthma. Surprisingly, a history of exacerbations did not impact on total IgE in women with COPD. Patients in the highest tertiles of total IgE (> 91.5 IU/ml, adjusted OR: 1.62, 95% CI 1.12-2.34) or allergen-specific IgE (> 0.19 IU/ml, adjusted OR: 2.15, 95% CI 1.32-3.51) were at risk of lung function decline (adjusted by: age, gender, body mass index, initial lung function, smoking status, history of asthma, history of allergy).ConclusionThese data suggest that IgE may play a role in specific COPD subgroups. Clinical trials using antibodies targeting the IgE pathway (such as omalizumab), especially in men with recurrent exacerbations and elevated serum IgE, could elucidate potential therapeutic implications of our observations.

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Leptin receptor polymorphisms and lung function decline in COPD.

Publications

Leptin receptor polymorphisms and lung function decline in COPD.

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