Brain-derived neurotrophic factor gene polymorphisms are associated with coronary artery disease-related depression and antidepressant response

Depression is a well-established risk factor for cardiac morbidity and mortality in patients with coronary artery disease (CAD). Previous studies have demonstrated that the level of brain-derived neurotrophic factor (BDNF) is decreased in depressed patients and this depletion may be reversed by antidepressants. Several recent studies have suggested that BDNF is involved in the pathogenesis of CAD. The aim of the present study was to investigate the possible association between seven single nucleotide polymorphisms (SNPs) of the BDNF gene (SNPs; rs16917204, rs6265, rs7103873, rs16917237, rs56164415, rs13306221 and rs10767664) and coronary artery disease-related depression (CAD-D). In the present study, 616 CAD patients without depression (CAD-nD) and 155 patients with CAD-D were recruited, and the response to an eight week sertraline antidepressant treatment regimen was also evaluated. The results demonstrated that a significant association existed between the SNP rs6265, located in exon 4 of the BDNF gene, and CAD-D [chi(2)=9.634, P=0.002, odds ratio (OR)=1.486, 95% confidence interval (CI)=1.156-1.910]. Another potential association was observed for rs13306221 (chi(2)=5.194, P=0.023, OR=2.139, 95% CI=1.096-4.175) in the promoter region of the BDNF gene. Strong linkage disequilibrium was observed in block 1 (rs16917204, rs6265; D'>0.9). However, there was no evidence of a significant linkage disequilibrium between the seven SNPs in our sample population. Additionally, carriers of the A allele of rs6265 exhibited improved responses to the sertraline treatment (chi(2)=8.942, P=0.003, OR=2.136, 95% CI=1.293-3.528). To the best of our knowledge, these results demonstrate, for the first time, the presence of a significant association between BDNF rs6265 and CAD-D, the identification of which may facilitate early diagnosis of CAD-D in the future.