In this study we also found that an intron 2 SNP, rs11503014 that is not in LD with any SNPs in haplotype blocks 1 or 2, was associated with heroin dependence. Rs11503014 is not located within a haplotype block in the three HapMap populations or within Finnish Caucasian and Plains Indian samples for which we have genotyped the same SNPs as in the present study (data not shown). Rs11503014 is located nearby to an alternatively spliced exon 2 and within an exon (5′ UTR) of the alternative GABRA2 transcript NM_001114175. The DNA sequence within which rs11503014 is located is similar to the exonic splicing enhancers: srp55, srp40, sf2 and sc35. Thus it is theoretically possible that rs11503014 may be implicated in exon splicing. Our results therefore suggest that GABRA2 may have at least two independent loci that are implicated in the vulnerability to heroin dependence.
