Association of polymorphisms in corticotropin-releasing hormone binding protein gene with selective serotonin reuptake inhibitors treatment response

Abstract

Objective To investigate whether the corticotropin-releasing hormone binding protein (CRHBP) gene polymorphisms is associated with the therapeutic response to selective serotonin reuptake inhibitors (SSRIs) in patients with major depressive disorder. Methods Routine dosage of SSRIs was given by six weeks to 207 patients who was diagnosed as major depressive disorder (MDD) according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-Ⅳ) criteria.The Hamilton Depression Rating Scale 17 (HAMD17) was used to assess the illness severity before and after the treatment.The patients were grouped into responder (reduction rate of HAMD17score≥50%) and non-responder (reduction rate of HAMD17score<50%).Taq Man MGB was used to analyze the differences of the 5 SNPs polymorphisms between the responder group and non-responder group. Results (1) At weeks 4,there was no statistically significant difference in the 5 CRHBP polymorphism genotypes,allele frequency and haplotype analysis between the two MDD groups with different responsiveness to SSRIs (P>0.05). (2) At weeks 6,allele frequency analysis of rs1715751 and rs32897 was statistically significant between the responder group and non-responder group (χ2=4.185,P=0.041,χ2=5.191,P=0.023).The frequency of CT+ CC genotype carriers of rs1715751 were higher in responder group than that in non-responder group (75/151,49.7% and 7/ 31,22.6% respectively,χ2=9.324,P=0.004; after Bonferroni Correction,P=0.020).The frequency of CT+ CC genotype of rs32897 in responder group was higher than that in non-responder group (63/151,41.7% and 7/31,22.6% respectively,χ2=4.905,P=0.029; after Bonferroni Correction,P=0.145). (3) At weeks 6,three haplotypes were associated with SSRIs therapeutic response in haplotype analyses including C-C (rs1715751-rs3792738,P=0.024;adjusted P=0.120; rs3792738-rs32897,P=0.013;adjusted P=0.065),C-C-C (rs1715751-rs3792738-rs32897,P=0.022; adjusted P=0.110). Conclusions The results support that CRHBP gene be involved in SSRIs therapeutic response in MDD. Key words: Polymorphism,single nucleotide; Serotonin uptake inhibitors; Treatment outcome; Corticotropin-releasing hormone binding protein gene