Abstract
The human chromosomal 5q31–33 region has been implicated as a susceptibility locus for several immune-mediated diseases including asthma in several populations. Recently, the extraneuronal GABAergic system has been implicated as a new link to airway obstruction in asthma. In addition, the SLC6A7 gene, which is positioned at 5q31–32 and encodes the transporter for an excitatory neurotransmitter of L-proline, has never been studied for its association with asthma. In this study, resequencing of all exon, promoter region (2 kb), and exon–intron boundary regions in the SLC6A7 gene found a total of 33 single nucleotide polymorphisms (SNPs) in 24 Korean asthmatic patients. After the initial SNP survey, a total of 17 common SNPs with minor allele frequency (MAF) over 10% were genotyped in 498 asthmatic patients and 303 normal controls. Logistic analyses revealed significant associations between genetic variants of the SLC6A7 gene and asthma (P-value up to 6.0 × 10−4; Pcorr value up to 0.009). In further regression analyses, minor alleles of intronic +11431T>C, +12213C>T and +12927A>G in linkage disequilibrium block 2 and +20113T>C in 3′UTR significantly increased the bronchodilator response in asthmatics (P-value of recessive model up to 0.008; which are not significant after multiple correction). Therefore, our findings suggest that SLC6A7 could be a susceptible gene for asthma.
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Acknowledgements
This work was supported by a grant from the Korea Health 21 R&D Project (A010249) and by Grant number M1-0302-00-0073 from the Korea Science and Engineering Foundation (KOSEF), funded by the Korean government (Ministry of Education, Science and Technology [MEST]) (No. 2009-0080157), and a Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0093822). The DNA samples were generously provided by the Soonchunhyang University, Bucheon Hospital Biobank, a member of the National Biobank of Korea, supported by the Ministry of Health, Welfare and Family Affairs, Republic of Korea.
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Kim, JH., Cheong, H., Park, BL. et al. A new association between polymorphisms of the SLC6A7 gene in the chromosome 5q31–32 region and asthma. J Hum Genet 55, 358–365 (2010). https://doi.org/10.1038/jhg.2010.34
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DOI: https://doi.org/10.1038/jhg.2010.34
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