Of considerable interest with regard to modulators explaining heterogeneity was the observation that among the 16 studies with allele frequency data the percentage of males in the study was found to be a significant predictor of the log OR (P = 0.023). This was not specifically discussed in the previous meta-analyses and to the best of our knowledge there are no reports in the literature citing gender differences in the occurrence of the A118G SNP. However, research has suggested a gender difference in analgesic response to opioids33 and recently, a gender difference in the reinforcing effect of nicotine has been reported, such that the G variant allele was associated with reduced reinforcement in women with no association in men (n = 60).34 Therefore, this potential impact of gender on the association warrants further investigation.
