Phillips-Bute Barbara, Mathew Joseph P, Blumenthal James A, Morris Richard W, Podgoreanu Mihai V, Smith Michael, Stafford-Smith Mark, Grocott Hilary P, Schwinn Debra A, Newman Mark F
Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
Psychosom Med. 2008 Nov;70(9):953-9. doi: 10.1097/PSY.0b013e318187aee6.
To assess genetic variability in two serotonin-related gene polymorphisms (MAOA-uVNTR and 5HTTLPR) and their relationships to depression and adverse cardiac events in a sample of patients undergoing coronary artery bypass surgery.
A total of 427 coronary artery bypass graft (CABG) patients were genotyped for two polymorphisms and assessed for depressive symptoms at three time points, in accordance with the Center for Epidemiological Studies-Depression (CES-D): preoperative baseline; 6 months postoperative; and 1 year postoperative. Logistic regression was used to assess the association between depressive symptoms (CES-D = >16), genotype differences, and cardiac events. Because MAOA-uVNTR is sex-linked, males and females were analyzed separately for this polymorphism; sexes were combined for the 5HTTLPR analysis.
Depressed patients were more likely than nondepressed patients to have a new cardiac event within 2 years of surgery (p < .0001); depressed patients who carry the long (L) allele of the 5HTTLPR polymorphism were more likely than the short/short (S/S carriers to have an event (p = .0002). Genetic associations with 6-month and 1-year postoperative depressive symptoms do not survive adjustment for baseline depressive symptoms.
A serotonin-related gene polymorphism--5HTTLPR--was associated with adverse cardiac events post CABG, in combination with depressive symptoms. Because depressed patients with the L allele of the 5HTTLPR polymorphism were more likely to have an event compared with the S/S carriers, combining genetic and psychiatric profiling may prove useful in identifying patients at the highest risk for adverse outcomes post CABG.
评估接受冠状动脉搭桥手术患者样本中两种血清素相关基因多态性（单胺氧化酶A基因可变数目串联重复序列[MAOA-uVNTR]和5羟色胺转运体基因启动子区多态性[5HTTLPR]）的基因变异性及其与抑郁症和不良心脏事件的关系。
对总共427例冠状动脉搭桥术（CABG）患者进行两种多态性的基因分型，并根据流行病学研究中心抑郁量表（CES-D）在三个时间点评估抑郁症状：术前基线；术后6个月；术后1年。采用逻辑回归分析评估抑郁症状（CES-D>16）、基因型差异与心脏事件之间的关联。由于MAOA-uVNTR是性连锁的，因此对该多态性分别分析男性和女性；对5HTTLPR分析则将两性合并。
与未患抑郁症的患者相比，抑郁症患者在术后2年内发生新的心脏事件的可能性更高（p<0.0001）；携带5HTTLPR多态性长（L）等位基因的抑郁症患者比短/短（S/S）携带者发生心脏事件的可能性更高（p=0.0002）。对基线抑郁症状进行校正后，与术后6个月和1年抑郁症状的基因关联不再显著。
一种血清素相关基因多态性——5HTTLPR——与冠状动脉搭桥术后的不良心脏事件相关，并伴有抑郁症状。由于携带5HTTLPR多态性L等位基因的抑郁症患者比S/S携带者发生心脏事件的可能性更高，因此将基因和精神状况分析相结合可能有助于识别冠状动脉搭桥术后不良结局风险最高的患者。
