Tabriz University of Medical Sciences Medical Journal of Tabriz University of Medical Sciences 2783-2031 48 1 2026 05 06 Analysis of the association linking the Val158Met polymorphism (rs4680) of the COMT gene and addiction to amphetamines and opioids in Iranian-Azeri Patients 24 33 10.34172/mj.026.35110 EN Shahrokh Amiri https://orcid.org/0000-0003-1676-7671 Narges Zeinalzadeh https://orcid.org/0000-0001-7222-3092 Sina Dezhampoor https://orcid.org/0000-0001-8834-418X Arash Mohagheghi https://orcid.org/0000-0003-0550-3101 Leila Mehdizadeh Fanid https://orcid.org/0000-0003-4935-4080 Nafiseh Zarezadeh https://orcid.org/0009-0003-9107-5314 Journal Article 10.34172/mj.026.35110 2025 08 25 2025 12 13 Background. Substance dependence, especially on amphetamines and opioids, is a major public health concern that is associated with alterations in the dopaminergic system. The COMT enzyme plays a key role in dopamine metabolism, and the Val158Met (rs4680) polymorphism may influence susceptibility to addiction. This study aimed to investigate the association of this polymorphism with amphetamine and opioid dependence in an Iranian-Azeri population. Methods. This case-control study was conducted including 150 individuals with substance dependence (133 males, 17 females) and 100 healthy controls (74 males, 26 females). Genotyping was performed using the PCR-RFLP method. Results. No significant differences were observed in the frequencies of genotypes and alleles between the groups (AA:P = 0.274, AG:P = 0.777, GG:P = 0.454; allele A:P =0.423, allele G:P =0.423). Conclusion. The findings indicate that the rs4680 variant of the COMT gene is not significantly associated with amphetamine or opioid dependence. Practical Implications. These results suggest that the rs4680 polymorphism alone is not a reliable marker for predicting genetic susceptibility to addiction in the Iranian-Azeri population. Therefore, using this variant in genetic screening without considering other genetic and environmental factors is not recommended. The present study underscores the need for larger-scale research investigating multiple genes and gene-environment interactions to better understand the genetic mechanisms underlying addiction.