DRD4 has also been investigated for association with methamphetamine dependence. Chen et al. (2004a) reported a higher frequency of the 7-repeat exon III VNTR allele in methamphetamine abusers as compared to controls, although the association did not reach statistical significance. A subsequent study utilizing the same population examined another VNTR polymorphism in the promoter region of DRD4, with a long (240 bp) and short allele (120 bp) (Li et al. 2004). Although no association between methamphetamine abuse and the promoter VNTR was found, when the promoter and exon III VNTR polymorphisms were analyzed as a haplotype, there was a significant association of the 7-repeat allele exon III VNTR and short promoter VNTR allele with methamphetamine abuse. Therefore, the 7-repeat allele of the exon III VNTR increases the dose of methylphenidate needed for therapeutic effects and may also increase the risk for development of methamphetamine abuse.
