It was found that only the heterozygous variant of COMT polymorphism (Val/Met) (p<0.05, OR = 1.66, 95% CI = 1.044–2.658) and both homozygous (p<0.05, OR = 0.43, 95% CI = 0.193–0.937) and heterozygous (p<0.05, OR = 0.37, 95% CI = 0.172–0.826) derived variants of DRD4 120 bp tandem duplication were significantly associated with risk of substance abuse compared to controls. Here, COMT is linked to substance abuse.