Members 6B and 14 of the TNF receptor superfamily in multiple sclerosis predisposition

Abstract

TNFRSF6B and TNFRSF14 genes were recently associated with Crohn's disease and rheumatoid arthritis. TNFRSF14 is known as herpes virus entry mediator (HVEM), and herpes viruses have been involved in the aetiology of multiple sclerosis (MS). MS patients present human herpes virus 6 (HHV6) in active plaques and increased antibody responses to HHV6. We aimed to ascertain the role of these genes in MS susceptibility and to investigate the relationship of the gene encoding the widely expressed HVEM receptor with the active replication of HHV6 found in some MS patients. Genotyping of 1370 Spanish MS patients and 1715 ethnically matched controls was performed. HHV6A DNA levels (surrogate of active viral replication) were analysed in serum of MS patients during a 2-year follow-up. Both polymorphisms were associated with MS predisposition, with stronger effect in patients with HHV6 active replication-TNFRSF6B-rs4809330*A: P ¼ 0.028, OR ¼ 1.13; TNFRSF14-rs6684865*A: overall P ¼ 0.0008, OR ¼ 1.2; and HHV6-positive patients vs controls: P ¼ 0.017, OR ¼ 1.69.

DcR3 gene polymorphisms are associated with sporadic breast infiltrating ductal carcinoma in Northeast Chinese women

“…Breast IDC is the most common breast cancer type in women. Previous research concerning DcR3 polymorphisms is scarce [ 19 , 20 ], especially with respect to cancer [ 21 ]. DcR3, as a member of the tumor necrosis factor superfamily of co-stimulatory molecules, promotes cellular invasion and migration in MCF7 breast cancer cells, and may be a negative regulator for aggressiveness during breast cancer development and progression [ 14 ].…”

Classification of HHV-6A and HHV-6B as distinct viruses

“…In addition, although an overwhelming majority of post-transplant reactivation occurs with HHV-6B [28, 29, 53], HHV-6A DNA and mRNA are found more frequently than HHV-6B in patients with neuroinflammatory diseases such as multiple sclerosis (MS) [9, 14, 48, 115] and rhomboencephalitis [37]. HHV-6A has been found predominantly in the CNS of a subset of patients with MS, and active HHV-6A infection has been detected in blood [8, 9, 11] and in CSF [110] of patients with relapsing/remitting MS [8–10, 14, 20, 110, 115, 131]. Marmosets inoculated with HHV-6A intravenously exhibited neurological symptoms, whereas those inoculated with HHV-6B were asymptomatic [75].…”

Variants of genes encoding TNF receptors and ligands and proteins regulating TNF activation in familial multiple sclerosis

“…A study of the gene found that the rs6684865 variant predisposed to MS, with a greater effect in patients positive for herpesvirus. 22 This gene also shows an association with MS susceptibility, according to a study by the International Multiple Sclerosis Genetics Consortium. 8 The above-mentioned polymorphism should be studied in the future.…”