Effect of serotonin receptor gene variants on substance use disorders.

Annals of medicine Pub Date : 2025-12-01 Epub Date: 2024-12-28 DOI:10.1080/07853890.2024.2445779
Laith Al-Eitan, Hana Abu Kharmah, Mansour Alghamdi
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Abstract

Background: Substance use disorders are multifaceted conditions influenced by both genetic and environmental factors. Serotonergic pathways are known to be involved in substance use disorder susceptibility, with genetic markers within serotonin receptor genes identified as potential risk factors.

Methods: To further explore this relationship, we conducted a study to investigate the association between several polymorphisms in five serotonin receptor genes (HTR1B, HTR2A/B, HTR3A/B) and substance use disorders (SUD) in Jordanian males by sequencing genotypes in 496 SUD patients and 496 healthy controls.

Results: Our findings revealed an allelic association between rs9567735 in the HTR2A gene and rs17586428 in the HTR2B gene with SUD. Haplotype analysis also showed that one haplotype of the HTR2A gene and four haplotypes of the five included genes were significantly associated with SUD risk. Moreover, we found that motives for substance use were correlated with single nucleotide polymorphisms SNPs rs1923882 and rs1150226, with the latter SNP also being associated with smoking.

Conclusion: These findings suggest that genetic variants of human 5-HT receptor genes may affect individual susceptibility to SUD in Jordan. However, further studies with larger sample sizes and additional variants in the same or different genes must confirm these findings.

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血清素受体基因变异对物质使用障碍的影响。
背景:物质使用障碍是受遗传和环境因素影响的多方面疾病。已知5 -羟色胺能通路与物质使用障碍易感性有关,5 -羟色胺受体基因中的遗传标记被确定为潜在的危险因素。方法:通过对496例物质使用障碍(SUD)患者和496名健康对照者进行基因型测序,研究5种血清素受体基因(HTR1B、HTR2A/B、HTR3A/B)多态性与约旦男性物质使用障碍(SUD)的关系。结果:我们发现HTR2A基因rs9567735和HTR2B基因rs17586428等位基因与SUD存在关联。单倍型分析还显示,HTR2A基因的1个单倍型和5个被纳入基因的4个单倍型与SUD风险显著相关。此外,我们发现药物使用的动机与单核苷酸多态性rs1923882和rs1150226相关,后者也与吸烟有关。结论:这些发现提示约旦人5-HT受体基因的遗传变异可能影响个体对SUD的易感性。然而,更大样本量的进一步研究和相同或不同基因的其他变异必须证实这些发现。
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