Length Polymorphisms in the Angiotensin I-Converting Enzyme Gene and the Serotonin-Transporter-Linked Polymorphic Region Constitute a Risk Haplotype for Depression in Patients with Coronary Artery Disease

Abstract

Genetic variations affecting the course of depressive symptoms in patients with coronary artery disease (CAD) have not yet been well studied. Therefore, we set out to investigate whether distinct haplotypes of the two insertion/deletion polymorphisms in the serotonin-transporter-linked polymorphic region (5-HTTLPR) and the angiotensin I-converting enzyme (ACE) gene located on chromosome 17 can be identified as risk factors for trajectories of depression. Clinical and genotyping data were derived from 507 depressed CAD patients participating in the randomized, controlled, multicenter Stepwise Psychotherapy Intervention for Reducing Risk in Coronary Artery Disease (SPIRR-CAD) trial, of whom the majority had an acute cardiac event before study inclusion. Depression scores on the Hospital Anxiety and Depression Scale (HADS) were assessed at baseline and at five follow-up time points up to 2 years after study entrance. At baseline, depression scores did not significantly differ between patients carrying the risk haplotype ACE D/D, 5-HTTLPR I/I (n = 46) and the non-risk haplotypes (n = 461, 10.9 ± 2.7 versus 10.4 ± 2.5, p = 0.254). HADS-depression scores declined from study inclusion during the first year irrespective of the genotype. At each follow-up time point, HADS-depression scores were significantly higher in ACE D/D, 5-HTTLPR I/I carriers than in their counterparts. Two years after study inclusion, the mean HADS depression score remained 1.8 points higher in patients with the risk haplotype as compared to subjects not carrying this haplotype (9.9 ± 4.2 versus 8.1 ± 4.0, p = 0.009). In summary, the presence of the ACE D/D, 5-HTTLPR I/I haplotype may be a vulnerability factor for comorbid depressive symptoms in CAD patients.

Serum Angiotensin-Converting Enzyme Methylation Level and Its Significance in Patients With Comorbid Major Depressive Disorder and Hypertension

“…A prior study further speculated a potential association between the abnormal methylation of the ACE2 promoter with the risk of essential HYT 29 . In addition, ACE gene located on chromosome 17 has been identified as an independent risk factor for depressive trajectory 30 . Collectively, our findings preliminarily highlighted ACE gene DNA methylation as an independent risk factor for patients with sMDD + HYT.…”

“…29 In addition, ACE gene located on chromosome 17 has been identified as an independent risk factor for depressive trajectory. 30 Collectively, our findings preliminarily highlighted ACE gene DNA methylation as an independent risk factor for patients with sMDD + HYT.…”

Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature

“…A number of genetic-related factors, genomic regions, polymorphisms, and other related aspects have been examined with respect to depression [ 61 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 ,...…”

Evaluation of 5-HTTLPR (insertion/deletion) and BDNF (rs6265) genetic variations in the Slovakian individuals suffering from affective disorders

“…Attention was also paid to the evaluation of 5-HTTLPR-affective disorder relationships in specific categories of patients suffering from somatic comorbidities. For example, LL genotype was found to be associated with the mean depression score in patients with coronary artery disease (Meyer et al 2020). Surprisingly, a recent meta-analysis has identified S allele as a predictive factor for developing depression among Asian and White patients with coronary artery disease (Zhang et al 2020).…”