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Sequence variation and linkage disequilibrium in the GABA transporter-1 gene (SLC6A1) in five populations: implications for pharmacogenetic research

Rungnapa Hirunsatit123, Risto Ilomäki4, Robert Malison1, Pirkko Räsänen4, Essi Ilomäki4, Henry R Kranzler5, Thomas Kosten12, Atapol Sughondhabirom6, Nuntika Thavichachart6, Sookjaroen Tangwongchai6, Jennifer Listman7, Apiwat Mutirangura8, Joel Gelernter12 and Jaakko Lappalainen12*

Author Affiliations

1 Yale University School of Medicine, Department of Psychiatry, New Haven, CT, USA

2 VA Connecticut Healthcare System, West Haven, CT, USA

3 Chulalongkorn University, Inter-Department Program of Biomedical Science, Faculty of Graduate School, Bangkok, Thailand

4 University of Oulu, Department of Psychiatry, Oulu, Finland

5 University of Connecticut School of Medicine, Department of Psychiatry, Farmington, CT, USA

6 Chulalongkorn University, Department of Psychiatry, Bangkok, Thailand

7 New York University, Department of Anthropology, New York, USA

8 Chulalongkorn University, Department of Anatomy, Bangkok, Thailand

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BMC Genetics 2007, 8:71  doi:10.1186/1471-2156-8-71

Published: 17 October 2007



GABA transporter-1 (GAT-1; genetic locus SLC6A1) is emerging as a novel target for treatment of neuropsychiatric disorders. To understand how population differences might influence strategies for pharmacogenetic studies, we identified patterns of genetic variation and linkage disequilibrium (LD) in SLC6A1 in five populations representing three continental groups.


We resequenced 12.4 kb of SLC6A1, including the promoters, exons and flanking intronic regions in African-American, Thai, Hmong, Finnish, and European-American subjects (total n = 40). LD in SLC6A1 was examined by genotyping 16 SNPs in larger samples. Sixty-three variants were identified through resequencing. Common population-specific variants were found in African-Americans, including a novel 21-bp promoter region variable number tandem repeat (VNTR), but no such variants were found in any of the other populations studied. Low levels of LD and the absence of major LD blocks were characteristic of all five populations. African-Americans had the highest genetic diversity. European-Americans and Finns did not differ in genetic diversity or LD patterns. Although the Hmong had the highest level of LD, our results suggest that a strategy based on the use of tag SNPs would not translate to a major improvement in genotyping efficiency.


Owing to the low level of LD and presence of recombination hotspots, SLC6A1 may be an example of a problematic gene for association and haplotype tagging-based genetic studies. The 21-bp promoter region VNTR polymorphism is a putatively functional candidate allele for studies focusing on variation in GAT-1 function in the African-American population.