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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 x 10(-4); P(corr) value up to 0.009). In further regression analyses, minor alleles of intronic +11431T&gt;C, +12213C&gt;T and +12927A&gt;G in linkage disequilibrium block 2 and +20113T&gt;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.

A new association between polymorphisms of the SLC6A7 gene in the chromosome 5q31–32 region and asthma