A functional brain-derived neurotrophic factor (BDNF) gene variant increases the risk of moderate-to-severe allergic rhinitis - 05/06/15
, De Yun Wang, MD, PhD r, ⁎ Abstract |
Background |
Brain-derived neurotrophic factor (BDNF) is a secretory protein that has been implicated in the pathogenesis of allergic rhinitis (AR), atopic asthma, and eczema, but it is currently unknown whether BDNF polymorphisms influence susceptibility to moderate-to-severe AR.
Objective |
We sought to identify disease associations and the functional effect of BDNF genetic variants in patients with moderate-to-severe AR.
Methods |
Tagging single nucleotide polymorphisms (SNPs) spanning the BDNF gene were selected from the human HapMap Han Chinese from Beijing (CHB) data set, and associations with moderate-to-severe AR were assessed in 2 independent cohorts of Chinese patients (2216 from Shandong province and 1239 living in Singapore). The functional effects of the BDNF genetic variants were determined by using both in vitro and ex vivo assays.
Results |
The tagging SNP rs10767664 was significantly associated with the risk of moderate-to-severe AR in both Singapore Chinese (P = .0017; odds ratio, 1.324) and Shandong Chinese populations (P = .039; odds ratio, 1.180). The coding nonsynonymous SNP rs6265 was in perfect linkage with rs10767664 and conferred increased BDNF protein secretion by a human cell line in vitro. Subjects bearing the AA genotype of rs10767664 exhibited increased risk of moderate-to-severe AR and displayed increased BDNF protein and total IgE levels in plasma. Using a large-scale expression quantitative trait locus study, we demonstrated that BDNF SNPs are significantly associated with altered BDNF concentrations in peripheral blood.
Conclusion |
A common genetic variant of the BDNF gene is associated with increased risk of moderate-to-severe AR, and the AA genotype is associated with increased BDNF mRNA levels in peripheral blood. Together, these data indicate that functional BDNF gene variants increase the risk of moderate-to-severe AR.
Le texte complet de cet article est disponible en PDF.Key words : Brain-derived neurotrophic factor, moderate-to-severe allergic rhinitis, Singapore Chinese, neurotrophins, genetic association
Abbreviations used : AR, BDNF, CHB, eQTL, HWE, Met, OR, SNP, tagSNP, Val
Plan
| Supported by grants from the Singapore Immunology Network (SIgN-06-006, SIgN-08-020 and SIgN-10-029); the National Medical Research Council of Singapore (NMRC/1150/2008); the Biomedical Research Council, Singapore; the Agency for Science, Technology and Research (A*STAR); the Science Development Funding Agency of Shandong Province, China (2010G0020258); and the National University of Singapore's Graduate Research Scholarship program, which supported students involved in the study. |
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| Disclosure of potential conflict of interest: This study was supported by grants from the Singapore Immunology Network (SIgN-06-006, SIgN-08-020 and SIgN-10-029); the National Medical Research Council of Singapore (NMRC/1150/2008); the Biomedical Research Council, Singapore; the Agency for Science, Technology and Research (A*STAR); the Science Development Funding Agency of Shandong Province, China (2010G0020258); and the National University of Singapore's Graduate Research Scholarship program, which supported the students involved in the study. SHIP-TREND-0: This cohort is part of the Community Medicine Research (CMR) net of the University of Greifswald, which is funded by the German Federal Ministry of Education and Research and the German Ministry of Cultural Affairs, as well as by the Social Ministry of the Federal State of Mecklenburg–West Pomerania. CMR encompasses several research projects that share data from the population-based Study of Health in Pomerania (SHIP; see URLs). Magnetic resonance imaging scans were supported by a joint grant from Siemens Healthcare, Erlangen, Germany, and the Federal State of Mecklenburg–West Pomerania. The SHIP authors are grateful to Mario Stanke for the opportunity to use his server cluster for SNP imputation, as well as to Holger Prokisch and Thomas Meitinger (HelmholtzZentrum München) for genotyping the SHIP-TREND cohort, which was supported by the Federal Ministry of Education and Research (grant 03ZIK012). F. T. Chew has received consultancy fees from Sime Darby Technology Centre and the National University of Singapore. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 135 - N° 6
P. 1486 - juin 2015 Retour au numéro
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