Polymorphisms in the Angiotensin-Converting Enzyme Gene Region Predict Coping Styles in Healthy Adults and Depressed Patients

Dispositional coping styles are important moderators of the stress reaction and are altered in stress-related disorders like cardiovascular diseases and affective disorders. Heritability studies suggest a considerable genetic contribution to the inter-individual variability in coping styles. Since the angiotensin-converting enzyme (ACE) gene has been described to be associated with the vulnerability for stress-related disorders and with altered stress hormone regulation, we investigated the ACE gene as potential candidate gene for coping styles. Five hundred forty one mentally healthy subjects and 194 patients suffering from depression participating in the Munich Antidepressant Response Signature (MARS) project were examined. Coping styles were assessed with a self-report questionnaire (German Stress Coping Questionnaire SVF78) measuring the individual coping style pattern in response to stressful situations. We genotyped 15 single nucleotide polymorphisms (SNPs) and the insertion/Deletion (I/D)-polymorphism in the ACE gene region and investigated their associations with coping styles. In healthy subjects, the highest association was observed between rs8066276, an intronic SNP of the ACE gene, and the coping factor Distraction. A further intronic SNP rs4305, not in linkage disequilibrium with rs8066276, showed an association with Devaluation/Defense. All associated copying styles can be categorized as potentially stress reducing factors (positive coping). Both SNPs were also found to be associated with positive coping styles in the patient sample; rs8066276 was associated with Devaluation/Defense and rs4305 showed associations with Control. These results suggest that the ACE gene is involved in the development of coping strategies. (C) 2008 Wiley-Liss, Inc.