RESUMO
The serotonin-transporter-linked polymorphic region (5-HTTLPR) gene has been reported to predispose individuals experiencing trauma to affective disorders such as anxiety and depression. We hypothesized that SS genotype of 5-HTTLPR gene would induce stress conditions and poor prognosis of papillary thyroid carcinoma (PTC). The study enrolled 287 patients with or without post-traumatic stress disorder (PTSD) following surgical treatment of PTC with their baseline characteristics collected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was conducted to detect genotype frequency. Five self-rating scales, including Impact of Event Scale-Revised Edition (IES-R), MedicaI Coping Modes Questionnaire (MCMO), Hamilton Depression Scale (HAMD), Social Support Rating Scale (SSRS) and Stressful Life Events (SLEs), were used for depressive state assessment. Survival situations were observed through 15-year follow-up visits one time every six months. Survival rate was calculated using Life Table. Logistic regression analysis was used to analyze factors related to prognosis of PTC. Increased SS genotype and decreased LL genotypes were found in patients with PTSD. PTSD is associated with high stress, and inter-group analysis revealed that patients carrying SS genotype exhibited a high stress condition. PTSD and SS genotype correlated to large tumor size, advanced clinical stage, lymph node metastasis, and decreased 10-year and 15-year survival rate. As for patients carrying the same genotype, those suffering from PTSD showed poorer survival. Also, 5-HTTPRL, MCMQ score (confrontation/avoidance/surrender), HAMD score, SSRS total score, SLEs score, tumor size, clinical stage, and lymph node metastasis were relevant factors for prognosis of PTC. The results demonstrate SS genotype of the 5-HTTPRL gene as a contributor of high stress among patients with PTC. Thus, 5-HTTPRL and stress conditions represent potential investigative focus targets for prognosis of PTC.
RESUMO
Posttraumatic stress disorder (PTSD) is a common response to traumatic events. Many PTSD patients recover in the next few months, but in a significant subgroup, the symptoms persist, often for years. The present study shows that brain-derived neurotrophic factor (BDNF) gene is related to the pathological mechanism of a variety of mental diseases. Here we investigate the effect of methylation of BDNF gene and different loci on the occurrence and development of PTSD. Initially, using case-control method, 322 PTSD patients as well as 215 normal controls were selected as the subjects. Following peripheral venous blood being collected from the subjects, genomic DNA was extracted. Methylation of the cytosine-guanine dinucleotide (CpG) island in BDNF gene promoter was then modified by bisulfite and detected through direct sequencing. Methylation of CpG in BDNF gene promoter was closely related to PTSD, and the methylation level of CpG in BDNF gene promoter may serve as a biomarker for PTSD diagnosis. Types of trauma of PTSD patients may have a certain effect on the methylation level of BDNF gene promoter. Methylation level of the BDNF promoter, depressive degree score, poor sleep quality score, early trauma score, mental stress score, and trauma type were closely related to the occurrence and development of PTSD. Taken together, our data support the notion that stressful life events may directly cause CpG methylation in the BDNF promoter of PTSD patients. Stress types may be associated with methylation levels of CpG1, CpG7, and CpG18 in the BDNF promoter of PTSD patients. These findings provide a new way for the diagnosis and treatment of PTSD.