Department of Psychiatry, Bellvitge University Hospital, c/Feixa Llarga S/N, Hospitalet de Llobregat, 08907, Barcelona, Spain.
Psychoneurobiology of Eating and Addictive Behaviors Group, Neurosciences Program, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain.
Sci Rep. 2022 Apr 28;12(1):6925. doi: 10.1038/s41598-022-10391-w.
Evidence about the involvement of genetic factors in the development of gambling disorder (GD) has been assessed. Among studies assessing heritability and biological vulnerability for GD, neurotrophin (NTF) genes have emerged as promising targets, since a growing literature showed a possible link between NTF and addiction-related disorders. Thus, we aimed to explore the role of NTF genes and GD with the hypothesis that some NTF gene polymorphisms could constitute biological risk factors. The sample included 166 patients with GD and 191 healthy controls. 36 single nucleotide polymorphisms (SNPs) from NTFs (NGF, NGFR, NTRK1, BDNF, NTRK2, NTF3, NTRK3, NTF4, CNTF and CNTFR) were selected and genotyped. Linkage disequilibrium (LD) and haplotype constructions were analyzed, in relationship with the presence of GD. Finally, regulatory elements overlapping the identified SNPs variants associated with GD were searched. The between groups comparisons of allele frequencies indicated that 6 SNPs were potentially associated with GD. Single and multiple-marker analyses showed a strong association between both NTF3 and NTRK2 genes, and GD. The present study supports the involvement of the NTF family in the aetiopathogenesis of GD. An altered cross-regulation of different NTF members signalling pathways might be considered as a biological vulnerability factor for GD.
已有研究评估了遗传因素在赌博障碍（GD）发展中的作用。在评估 GD 的遗传力和生物学易感性的研究中，神经生长因子（NTF）基因已成为有前途的靶点，因为越来越多的文献表明 NTF 与成瘾相关疾病之间可能存在联系。因此，我们旨在探索 NTF 基因与 GD 的关系，假设某些 NTF 基因多态性可能构成生物学风险因素。该样本包括 166 名 GD 患者和 191 名健康对照。选择了 NTF（NGF、NGFR、NTRK1、BDNF、NTRK2、NTF3、NTRK3、NTF4、CNTF 和 CNTFR）中的 36 个单核苷酸多态性（SNP）并进行了基因分型。分析了连锁不平衡（LD）和单倍型构建，与 GD 的存在有关。最后，搜索了与 GD 相关的鉴定 SNP 变体重叠的调控元件。等位基因频率的组间比较表明，有 6 个 SNP 可能与 GD 有关。单标记和多标记分析显示，NTF3 和 NTRK2 基因与 GD 之间存在强烈关联。本研究支持 NTF 家族在 GD 的发病机制中的作用。不同 NTF 成员信号通路的交叉调节改变可能被认为是 GD 的生物学脆弱性因素。
