title: A new association between polymorphisms of the SLC6A7 gene in the chromosome 5q31-32 region and asthma.
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 x 10(-4); P(corr) 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.
authors.affiliation: Department of Life Science, Sogang University, Seoul, Republic of Korea.
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.forename: Byung-Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Joon Seol
authors.initials: JS
authors.lastname: Bae
authors.forename: Seok
authors.initials: S
authors.lastname: Jung
authors.forename: Sang-Hyuk
authors.initials: SH
authors.lastname: Yoon
authors.forename: Jong Sook
authors.initials: JS
authors.lastname: Park
authors.forename: An Soo
authors.initials: AS
authors.lastname: Jang
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Soo-Taek
authors.initials: ST
authors.lastname: Uh
authors.forename: Yong-Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Hyeon-Kyu
authors.initials: HK
authors.lastname: Hwang
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics*; D001249:Asthma / Q000235:genetics*; D002648:Child; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D055815:Young Adult
chemical_list: D026921:Amino Acid Transport Systems, Neutral; C041832:proline transport protein