Clinical Interventions in Aging (Jul 2019)
Y chromosome loss is associated with age-related male patients with abdominal aortic aneurysms
Abstract
Dianjun Tang,*,1,2 Yanshuo Han,*,3 Yu Lun,1 Han Jiang,1 Shijie Xin,1 Zhiquan Duan,1 Jian Zhang11Department of Vascular Surgery, The First Hospital of China Medical University, Key Laboratory of Pathogenesis, Prevention and Therapeutics of Aortic Aneurysm Liaoning Province, Shenyang, People’s Republic of China; 2Department of Vascular Surgery, The Second Hospital of Shandong University, Jinan, People’s Republic of China; 3Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China*These authors contributed equally to this workPurpose: Abdominal aortic aneurysm (AAA) demonstrates many features of autoimmune diseases. Y chromosome, sex-determining region of the Y chromosome (SRY) gene, androgen receptor (AR) gene, and androgen appear as potential candidates for influence of the male immune function. This study investigated Y chromosome numbers, SRY gene, AR gene, and androgen levels in male AAAs. We also investigated the correlation between Y chromosome loss (LOY) ratio, SRY expression, androgen levels, and age.Patients and methods: We investigated LOY by fluorescence in situ hybridization (FISH) in 37 AAAs and compared with 12 patients with abdominal aortic atherosclerotic occlusive disease (AOD) and 91 healthy controls (HC). We investigated SRY and AR expression at mRNA level by real-time PCR in peripheral T lymphocytes in AAA compared with AOD and HC, and AR protein levels by immunohistochemistry (IHC) in AAA. LOY, SRY expression, androgen levels, and age were examined for correlations using the Spearman’s rank correlation coefficient.Results: LOY ratio in peripheral T lymphocytes was significantly higher in the AAA group compared with the HC (9.11% vs 5.56%, P<0.001) and AOD groups (9.11% vs 6.42%, P=0.029). The SRY mRNA expression in peripheral T lymphocytes was 4.7-fold lower expressed in the AAA group than in the HC group (P<0.001). Free plasma testosterone levels were lower in the AAA group compared with the HC group (P=0.036), whereas sex hormone-binding globulin levels were higher (P=0.020). LOY ratio and expression of SRY mRNA level increased with age in the AAA group (R=0.402 and, R=0.366, respectively). A significant correlation between AR mRNA level (R=0.692) and aortic diameter was detected. Simultaneously, in AAA tissue, the rate of LOY increased with age (R=0.547) and also positively associated with LOY in peripheral blood T lymphocytes (R=0.661).Conclusion: This study identified a prominent Y chromosome loss in male AAAs, which is correlated to age, lower level of SRY expression and free testosterone, providing a new clue for the mechanisms of AAA.Keywords: abdominal aortic aneurysm, age-related, Y chromosome, sex-determining region of the Y chromosome (SRY), testosterone
