Slitrk Family And Brain-derived Neurotrophic Factor Gene In Obsessive-Compulsive Disorder

[Objective] To explore the role of Slitrk family and Brain-derived neurotrophic factor(BDNF) gene in the mechanism of Obsessive-Compulsive Disorder(OCD).[Methods]1. Molecular genetics study of Slitrk family and BDNF gene in OCD:We compared Slitrk1、Slitrk5、BDNF、mi R-195、mi R-30a-5p gene single nucleotide polymorphism rs9531519、rs9582391、rs6265、rs78312845、rs2222722 genotypic and allelic distribution between 636 OCD patients and 612 healthy people(NC, Normal Control).We compared Slitrk1、Slitrk5、BDNF gene expression levels between 40 OCD patients and 16 normal controls.2. Imaging genetics study of Slitrk family and BDNF gene in OCD:We compared gray matter volumn between 23 OCD patients and 16 normal controls.We compared certain brain region volumn found in the last step between participants carrying different alleles in each group.[Results] 1. Molecular genetics study of Slitrk family and BDNF gene in OCD:1) There was no difference among Slitrk1 SNP rs9531519、Slitrk5 SNP rs9582391、BDNF SNP rs6265、mi R-30a-5p SNP rs2222722 genotypic and allelic distribution in OCD patients and normal controls(p>0.05).(The genotype frequencies of mi R-195 SNP rs78312845 were not in Hardy-Weinberg equilibrium. So we deleted this SNP.)2) Slitrk5 SNP rs9582391 genotypic distribution in late-onset OCD patients was different from that in normal controls(χ2=6.266,p=0.044). Late-onset OCD patients carried less allele A(genotyped as AA/CA) than NC. Although the difference was no longer significant after FDR correction(q=0.176).3) Y-BOCS scores of OCD patients were different among who carrying different genotypes of Slitrk5 SNP rs9582391(F=3.421,p =0.033).4) Slitrk1、Slitrk5 and BDNF gene expression levels in OCD patients were not different from those in normal controls(Slitrk1 fold change=-1.01, p=0.500, q=0.500; Slitrk5 fold change=-1.07, p=0.032, q=0.096; BDNF fold change=1.01, p=0.498, q=0.747). 2. Imaging genetics study of Slitrk family and BDNF gene in OCD:1) Voxel-Based Morphometry(VBM) analysis showed that the volumn of midbrain, left pallidum, caudate head, supramarginal gyrus, right angular, temporal lobe, occipital lobe, cuneus in OCD patients were larger than those in normal controls.2) OCD patients carrying different genotypes of Slitrk1 SNP rs9531519 showed different midbrain volume(F=9.116, p=0.002); normal controls carrying different genotypes of mi R-30a-5p SNP rs2222722 showed different midbrain volume(F=4.153, p=0.045).[Conclusion]1. Slitrk5 gene influence the severity of OCD: Y-BOCS scores are different among OCD patients carrying different genotypes of Slitrk5 SNP rs9582391.2. Slitrk1 gene probably influences the structure of midbrain beyond cortico-striatal circuit which leading to OCD.3. Our results do not support that the genotypic frenquency of BDNF SNP rs6265 and mi R-30a-5p SNP rs2222722 and BDNF genetic expression levels are different between OCD patients and normal controls. Also our results do not support that OCD patients carring different genotyps show different brain gray matter volumn.