T-cell immunoglobulin- and mucin-domain-containing molecule 3 genetic variants and HIV+ non-hodgkin lymphomas

摘要

T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) has been established as a negative regulatory molecule and plays a critical role in inflammatory diseases such as rheumatoid arthritis, hepatitis B and C, and human immunodeficiency virus (HIV)-related inflammation. Recent studies have shown that chronic inflammation may greatly affect the pathogenesis of non-Hodgkin lymphomas (NHL). The aim of this study was to investigate whether polymorphisms in the TIM-3 gene were associated with susceptibility to non-NHL and HIV-related NHL. Three polymorphisms in TIM-3 gene (-1516G/T, -574G/T, and +4259T/G) were identified by polymerase chain reaction-restriction fragment length polymorphism in 434 NHL patients, 62 HIV-related NHL cases, and 512 healthy controls. Results showed that the prevalence of -574GT genotype and +4259TG genotype were significantly increased in the NHL cases than in controls (odds ratio (OR) = 2.72, 95 % confidence interval (CI) = 1.50-4.92, p = 0.0006 and OR = 2.59, 95 % CI = 1.49-4.49, p = 0.0005, respectively). The -1516G/T polymorphism did not reveal significant difference between patients and healthy controls. When analyzing the TIM-3 polymorphisms in HIV-related NHL patients, data showed that HIV+ NHL patients had higher prevalence of -574GT or +4259TG genotypes than those cases without HIV infection (OR = 3.48, 95 % CI = 1.67-7.28, p = 0.0005 and OR = 2.92, 95 % CI = 1.42-6.01, p = 0.0026, respectively). These results suggested polymorphisms in TIM-3 gene could be new risk factors for NHL as well as HIV-related NHL and suggested a possible role of the inflammatory factor in these diseases.