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OBJECTIVE: Nicotine is the main addictive agent present in tobacco and is principally metabolized by a cytochrome P450-mediated oxidation process. While smoking patterns differ widely among smokers, the metabolization rate of nicotine can also be affected by variations in rates of enzyme activity between individuals. Therefore, we aimed to investigate the significance of CYP2A gene variants in the smoking status in a Turkish population using next-generation sequencing (NGS). METHODS: This case–control study involved 64 subjects with Nicotine dependence (ND) and 36 Non-smoker (NS) subjects. Amplicants designed by “Primer-BLAST” programme were all sequenced using the “Illimuna-MiseqQ-platform”. RESULTS: It was found that there were five SNPs in the CYP2A6 gene (rs8192725, rs7248240, rs1809810, rs8192733 and rs28399435). CYP2A6 rs1809810 homozygous TT genotype and T allele were seen in lower percentages in ND group compared to the NS group (p = 0.045; p = 0.021). Individuals with CYP2A6 rs1809810 TT genotypes and T allele showed odds ratio of 4.760 and 5.360 for developing protective role ND, respectively. CYP2A6 rs8192733 CC genotype and C allele were both lower in ND group (respectively p = 0.001, p = 0.023) while GC genotype was higher in the ND group (p = 0.004). CYP2A6 rs28399435 TT genotype and T allele were more common in the ND group (respectively p = 0.001, p = 0.001). CYP2A6 rs28399435 CC genotype was lower in the ND group than in the NS group (p = 0.010). CONCLUSIONS: CYP2A6 rs1809810, rs8192733, rs28399435 could be genetic risk factors for ND in a Turkish population.

OBJECTIVE: Substance use disorder (SUD) has important effects on health and well-being. It is well known that genetic factors play a role in SUD. The purpose of this research was to investigate whether functional variants of DNA repair genes might be a risk factor for cannabis and/or synthetic cannabis dependence in a Turkish cohort. METHODS: In total, 131 patients with cannabis and/or synthetic dependence and 70 healthy controls were included in this case–control study. XRCC1 codon 399 (rs25487) and XRCC4 G1394 T (rs6869366), and XPD (rs13181) variants were determined by the polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). RESULTS: The XRCC1 rs25487 GG genotype and G allele were significantly lower in patients compared to controls (p = 0.005; p = 0.002, respectively). XRCC4 rs6869366 TT genotype and T allele were more common in patients compared to controls (p = 0.001, p = 0.001, respectively). It was found that patients with XPD rs13181 Lys/Gln had a significantly higher risk of cannabis dependence than control did (p = 0.00). The subjects carried XPD rs13181 Gln/Gln genotype had a 2.2-fold increased risk for cannabis dependence (p = 0.010). CONCLUSIONS: We demonstrated for the first time that DNA repair gene variants may alter individual vulnerability for SUD. This observation could be of further interest to researchers, as it could suggest new candidate genes, presumably crucial for the etiopathogenesis of the cannabis and/or synthetic cannabis dependence.