Alonso P, Gratacòs M, Menchón J M, Segalàs C, González J R, Labad J, Bayés M, Real E, de Cid R, Pertusa A, Escaramís G, Vallejo J, Estivill X
OCD Clinical and Research Unit, Psychiatry Department, Hospital Universitari de Bellvitge, Feixa Llarga s/n, L'Hospitalet de Llobregat, Barcelona, Spain.
Genes Brain Behav. 2008 Oct;7(7):778-85. doi: 10.1111/j.1601-183X.2008.00418.x. Epub 2008 Jul 28.
Recent work suggests that neurotrophic factors may contribute to the genetic susceptibility to obsessive-compulsive disorder (OCD). Among other clinical dimensions, the presence of hoarding obsessions and compulsions has been shown to be correlated with a number of clinical and neuroimaging findings, as well as with a different pattern of genetic inheritance. We used a linkage disequilibrium (LD)-mapping approach to investigate whether neurotrophic tyrosine kinase receptor type 3 (NTRK3), the high-affinity receptor of neurotrophin 3 (NT-3), plays a role in increasing susceptibility to hoarding in OCD. We performed an association study of 52 tag single nucleotide polymorphisms (tagSNPs) covering the whole NTRK3 gene in a sample comprising 120 OCD patients and 342 controls. Single nucleotide polymorphism association and haplotype analysis were performed. Thirty-six of our patients (30%) exhibited significant hoarding obsessions and compulsions. A significant association of two SNPs in the 3' downstream region of NTRK3 gene and obsessive-compulsive hoarding was identified: rs1017412 [odds ratio (OR) = 2.16; P = 0.001] and rs7176429 (OR = 2.78; P = 0.0001), although only the latter remained significant after Bonferroni correction. Although the haplotype analysis did not show significant results, a more extended block of LD in the OCD hoarders with respect to the control group was observed, suggesting a lower haplotype diversity in these individuals. Our findings suggest that NTRK3 may contribute to the genetic susceptibility to hoarding in OCD and may constitute an interesting gene to focus on in studies of the genetic basis of obsessive-compulsive hoarding.
近期研究表明，神经营养因子可能与强迫症（OCD）的遗传易感性有关。在其他临床维度中，囤积观念和行为的存在已被证明与一些临床和神经影像学发现相关，也与不同的遗传模式有关。我们采用连锁不平衡（LD）定位方法，研究神经营养酪氨酸激酶受体3型（NTRK3），即神经营养因子3（NT-3）的高亲和力受体，是否在增加OCD患者囤积行为易感性中发挥作用。我们对120例OCD患者和342名对照组成的样本，进行了覆盖整个NTRK3基因的52个标签单核苷酸多态性（tagSNP）的关联研究。进行了单核苷酸多态性关联和单倍型分析。我们的36例患者（30%）表现出明显的囤积观念和行为。在NTRK3基因3'下游区域，发现两个SNP与强迫性囤积显著相关：rs1017412 [优势比（OR）= 2.16；P = 0.001]和rs7176429（OR = 2.78；P = 0.0001），不过经Bonferroni校正后，只有后者仍具有显著性。虽然单倍型分析未显示显著结果，但在OCD囤积者中观察到相对于对照组有更广泛的LD区域，表明这些个体的单倍型多样性较低。我们的研究结果表明，NTRK3可能与OCD患者囤积行为的遗传易感性有关，可能是强迫症囤积行为遗传基础研究中一个值得关注的有趣基因。
