Polymorphism And Transcriptional Regulation Of SIRT1 Gene In Patients With Diffuse Large B Cell Lymphoma

Objective:1.To explore the relationship between SIRT1 gene single nucleotide polymorphism(SNP)rs3758391 and diffuse large B-cell lymphoma(DLBCL)in Chinese Han population.2.To explore the relationship between SIRT1 mRNA expression and Diffuse large B cell lymphoma(DLBCL)in Chinese Han population.Methods:1.Patients diagnosed with DLBCL according to the World Health Organization classification at Tianjin Medical University Cancer Institute and Hospital and Ningbo No.2 Hospital from 2011 to 2013 and healthy individuals were recruited in the study.Peripheral blood specimens were collected from 206 DLBCL patients and 219 healthy people as controls.Pathological tissues of 58 DLBCL patients and 30 cases of reactive hyperplastic lymph node tissues were collected.2.Genomic DNA was isolated from peripheral blood samples of DLBCL patients and healthy controls.The genotyping of SIRT1 rs3758391 polymorphism was detected by restriction fragment length polymorphism polymerase chain reaction(PCR-RFLP).3.RNA was extracted from DLBCL patients with diffuse large B-cell lymphoma and reactive hyperplastic lymph node tissues.The expression of SIRT1 mRNA was detected by quantitative real-time polymerase chain reaction(qRT-PCR).4.All statistical analyses were performed using IBM SPSS Statistics version 20.0,all tests were two sides and p<0.05 was considered to indicate statistically significant.Results:1.The genotype TT and allele T frequency were significantly higher in DLBCL patients than that of controls(p = 0.02 and 0.01,respectively).2.No statistical differences were observed between SIRT1 rs3758391 and clinical characteristics of DLBCL patients.3.Analysis of the polymorphism revealed an increased risk of DLBCL associated with TC and TT genotype when compared with CC genotype [odds ratio = 2.621 and 3.518,respectively;95% confidence interval(CI)1.249–5.501 and 1.675–7.390,respectively;p = 0.011 and 0.001,respectively].4.The survival analysis indicated that the patients with genotype TT/TC had higher overall survival rate than those with genotype TT(p = 0.005).5.Multivariate Cox regression analysis showed that the TT genotype of SIRT1 SNP rs3758391 was an independent poor prognostic factor for DLBCL patients(p = 0.006,HR 1.981,95% CI 1.215–3.231).6.The SIRT1 mRNA expression was significantly upregulated in DLBCL patients than that of controls(p < 0.001).In addition,the SIRT1 mRNA expression of TT subgroup was upregulated compared with TC/CC subgroup in DLBCL patients(p < 0.001).7.The survival analysis showed that the patients with lower SIRT1 mRNA level(below the median)had higher 5-year overall survival rate than those with higher SIRT1 mRNA level(below the median)(p = 0.032).Conclusion:Genotype TT/TC of SIRT1 gene rs3758391 increased the risk of diffuse large B-cell lymphoma in a Chinese Han population,compared with genotype CC.The Chinese Han population with genotype TT would show worse survival than those with genotype TC/CC when suffer DLBCL.Chinese Han population with lower SIRT1 mRNA level would show better overall survival than those with higher SIRT1 mRNA level.The SIRT1 gene may be a biomarker for the diagnosis and prognosis of DLBCL.