PMID- 19191138 OWN - NLM STAT- MEDLINE DCOM- 20090220 LR - 20220408 IS - 1532-4303 (Electronic) IS - 0277-0903 (Linking) VI - 46 IP - 1 DP - 2009 Feb TI - Are genes associated with energy metabolism important in asthma and BMI? PG - 53-8 LID - 10.1080/02770900802460514 [doi] AB - OBJECTIVE: Increased serum leptin levels have been observed in asthmatic patients. Leptin, via proliferation and activation of Th2 cells, may induce inflammation in asthma. It has also been demonstrated that leptin mRNA expression and protein levels increase in response to inflammatory stimuli. We hypothesized that polymorphisms in the leptin receptor, leptin and ghrelin genes, may affect their expression and, therefore, be responsible for altered response to increased leptin levels observed in asthma. To our knowledge, there were no studies on a potential role of LEPR, LEP, and GHRL polymorphisms in asthma. SUBJECTS AND METHODS: We analyzed 129 pediatric patients with asthma and 114 healthy children from the control group ranging from 6 to 18 years of age. The diagnosis of allergic asthma was based on clinical symptoms, the lung function test, and the positive skin prick test and/or increased immunoglobulin E (IgE) levels. Polymorphisms were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Statistical analyses were performed with Statistica v.7.1 software (Statistica, StatSoft, Poland; available free at http://www.broad.mit.edu/mpg/haploview/index.php). Linkage disequilibrium analysis was performed with Haploview v.4.0. RESULTS: We observed a statistically significant association of the 3'UTR A/G and the -2549A/G polymorphisms of the leptin gene with asthma. No association with asthma was observed for the K109R and the Q223R polymorphisms of the LEPR gene and the Met72Leu polymorphism of the ghrelin gene. In the analysis of body mass index (BMI) stratified by genotype, we found an association of the -2549A/G LEP, but not of LEPR and GHRL polymorphisms, with higher BMI values in asthmatic patients. We found suggestive evidence for linkage between the two polymorphisms of the LEPR gene (D' = 0.84 CI: 0.71-0.92; r(2) = 0.29) in linkage disequilibrium analysis: The GG haplotype was more frequent in the control healthy group (p = 0.057). No linkage disequilibrium was detected between LEP polymorphisms. CONCLUSIONS: Polymorphisms of the leptin gene may be associated with asthma and higher BMI in asthmatic patients. Polymorphisms of the LEPR and GHRL seem unlikely to be associated with asthma or BMI in our sample. The results of haplotype analysis for the LEPR gene may suggest a protective role of the GG haplotype against asthma; however, studies on larger groups are necessary to confirm the observed trend towards association. FAU - Szczepankiewicz, Aleksandra AU - Szczepankiewicz A AD - Clinics of Pediatric Pulmonology, Allergy and Clinical Immunology, Poznan University of Medical Sciences, Poznan, Poland. alszczep@amp.edu.pl FAU - Breborowicz, Anna AU - Breborowicz A FAU - Sobkowiak, Paulina AU - Sobkowiak P FAU - Popiel, Anna AU - Popiel A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Asthma JT - The Journal of asthma : official journal of the Association for the Care of Asthma JID - 8106454 RN - 0 (Ghrelin) RN - 0 (Leptin) RN - 0 (Receptors, Leptin) SB - IM MH - Adolescent MH - Asthma/*genetics/metabolism MH - *Body Mass Index MH - Child MH - Energy Metabolism MH - Female MH - Gene Frequency MH - Genotype MH - Ghrelin/*genetics MH - Haplotypes MH - Humans MH - Leptin/*genetics MH - Linkage Disequilibrium MH - Male MH - Poland MH - Polymorphism, Single Nucleotide MH - Receptors, Leptin/*genetics EDAT- 2009/02/05 09:00 MHDA- 2009/02/21 09:00 CRDT- 2009/02/05 09:00 PHST- 2009/02/05 09:00 [entrez] PHST- 2009/02/05 09:00 [pubmed] PHST- 2009/02/21 09:00 [medline] AID - 908458384 [pii] AID - 10.1080/02770900802460514 [doi] PST - ppublish SO - J Asthma. 2009 Feb;46(1):53-8. doi: 10.1080/02770900802460514.