1) The associations found could be related more to the progression and severity of heroin dependence than vulnerability to this disorder [28], because patients had a long history of heroin use; 2) Type II error is a potential explanation for our findings, since the differences detected did not reach the significance threshold (i.e.: P < 0.008) when the Bonferroni correction was applied to the six genetic comparisons performed (Tables 2 and 3); however, type II error could occur in any direction (i.e., either A1 or A2 could have been associated with heroin use), while we found that the associated allele was A1, just as in previous reports; 3) The male-limited association of A1 allele with heroin dependence must be considered as a preliminary finding, because more males than females participated in the present study and there is no indication of gender dimorphism in regard with the TaqI A alleles in the literature; 4) The findings of the present study may not be generalizable, because all study participants belonged to the same population. Still, Spaniards are closely related to the other European populations, and one would not expect to find many differences in the genetic architecture of susceptibility to heroin use.
