Association between Fas/FasL gene polymorphism and musculoskeletal degenerative diseases: a meta-analysis

Abstract

BackgroundIt was reported that Fas (rs1800682, rs2234767) and FasL (rs5030772, rs763110) gene polymorphism might be related to the risk of musculoskeletal degenerative diseases (MSDD), such as osteoarthritis (OA), intervertebral disc degeneration (IVDD) and rheumatoid arthritis (RA). However, data from different studies was inconsistent. Here we aim to elaborately summarize and explore the association between the Fas (rs1800682, rs2234767) and FasL (rs5030772, rs763110) and MSDD.MethodsLiteratures were selected from PubMed, Web of Science, Embase, Scopus and Medline in English and VIP, SinoMed, Wanfang and the China National Knowledge Infrastructure (CNKI) in Chinese up to August 21, 2017. All the researches included are case-control studies about human. We calculated the pooled odds ratios (ORs) with 95% confidence intervals (95% CI) to evaluate the strengths of the associations of Fas (rs1800682, rs2234767) and FasL (rs5030772, rs763110) polymorphisms with MSDD risk.ResultsEleven eligible studies for rs1800682 with 1930 cases and 1720 controls, 6 eligible studies for rs2234767 with 1794 cases and 1909 controls, 3 eligible studies for rs5030772 with 367 cases and 313 controls and 8 eligible studies for rs763110 with 2010 cases and 2105 controls were included in this analysis. The results showed that the G allele of Fas (rs1800682) is associated with an increased risk of IVDD in homozygote and recessive models. The G allele of Fas (rs2234767) is linked to a decreased risk of RA but an enhanced risk of OA in allele and recessive models. In addition, the T allele of FasL (rs763110) is correlated with a reduced risk of IVDD in all of models. However, no relationship was found between FasL (rs5030772) and these three types of MSDD in any models.ConclusionsFas (rs1800682) and FasL (rs763110) polymorphism were associated with the risk of IVDD and Fas (rs2234767) was correlated to the susceptibility of OA and RA. Fas (rs1800682) and Fas (rs2234767) are more likely to be associated with MSDD for Chinese people. FasL (rs763110) is related to the progression of MSDD for both Caucasoid and Chinese race groups. But FasL (rs5030772) might not be associated with any types of MSDD or any race groups statistically.Electronic supplementary materialThe online version of this article (10.1186/s12891-018-2057-z) contains supplementary material, which is available to authorized users.

A Cell’s Fate: An Overview of the Molecular Biology and Genetics of Apoptosis

“…Polymorphisms in FAS gene may decrease the apoptotic potential of the receptor, and have been associated with several illnesses, including cancer and musculoskeletal degenerative disorders [100,101]. Furthermore, there are studies demonstrating the association of FAS polymorphisms with the persistence of HTLV infections and its clinical manifestations, such as Adult T-Cell Leukemia (ATL) and HTLV-1-associated myelopathy (HAM) [102,103,104].…”

Role of Caspase Family in Intervertebral Disc Degeneration and Its Therapeutic Prospects

“…Activated caspase-8 activates downstream caspase-3 to trigger the caspase apoptosis cascade and promote cell apoptosis ( Figure 2 ). Some researchers have revealed a close association between Fas/FasL gene polymorphisms and musculoskeletal degenerative diseases through meta-analysis, among which the Fas (rs1800682) and FasL (rs763110) polymorphisms are associated with the susceptibility to IVDD [ 58 ]. In herniated lumbar IVDs, IVD cells activate the Fas/FasL signaling pathway to promote IVD cell apoptosis through autocrine or paracrine FasL [ 59 ], and Fas may be involved in apoptosis of notochord cells in NP [ 60 ].…”

Targeted therapy for intervertebral disc degeneration: inhibiting apoptosis is a promising treatment strategy

“…Since FasL expression in IDD is reduced, most scholars believe that FasL expression by NPCs has a protective effect on IVDs 44 . Huang et al 45 reported that the Fas G allele (rs1800682) increased the risk of IDD, and the FasL T allele (rs763110) had the opposite effect. However, there are different views: FasL is harmful to IVDs 46 .…”