Association of TNFSF4 rs1234315, rs2205960 polymorphisms and systemic lupus erythematosus susceptibility: a meta-analysis

Abstract

Background The aim of this study was to explore the association between tumor necrosis factor superfamily number 4 (TNFSF4) rs1234315, rs2205960 polymorphisms and systemic lupus erythematosus (SLE) susceptibility. Methods A meta-analysis was performed on the association between rs1234315 and rs2205960 polymorphisms and SLE by allelic contrast, additive model, recessive model and dominant model. Results Regarding rs1234315 polymorphism, a total of five studies were included (6575 cases, 14,798 controls). Meta-analysis showed significant associations between the T allele and SLE in overall subjects and Asians (OR = 1.310, 95%CI: 1.104–1.553, p = 0.002; OR = 1.458, 95%CI: 1.328–1.602, p < 0.001). With respect to the rs2205960 polymorphism, significant associations between the T allele and SLE were found in all subjects (OR = 1.333, 95%CI: 1.254–1.418, p < 0.001), Asians (OR = 1.407, 95%CI: 1.345–1.471, p < 0.001) and Europeans (OR = 1.254, 95%CI: 1.185–1.328, p < 0.001). Results also showed significant associations between the additive model and SLE in all subjects and Asians (OR = 1.934, 95%CI: 1.500–2.494, p < 0.001; OR = 1.882, 95%CI: 1.318–2.689, p = 0.001). Furthermore, we detected significant associations between the dominant model and SLE in all subjects and Asians (OR = 1.421, 95%CI: 1.239–1.629, p < 0.001; OR = 1.297, 95%CI: 1.083–1.555, p = 0.005). Significant associations were found between the recessive model and SLE in overall subjects and Asians (OR = 1.677, 95%CI: 1.312–2.144, p < 0.001; OR = 1.751, 95%CI: 1.235–2.483, p = 0.002). Conclusion The present study suggested that TNFSF4 rs1234315 and rs2205960 polymorphisms were associated with SLE susceptibility.

Single-Nucleotide Polymorphism of Tnfsf4 (Rs2205960) of Systemic Lupus Erythematosus Patients in Bandung, Indonesia

“…These differences reflect the genetic heterogeneity of SLE among the world populations [10]. Another meta-analysis was carried out by Wang et al (2019) and Lee et al (2012) stated similar results, which found a significant association between the T allele of rs2205960 and SLE in all European and Asian subjects. A significant association was also found in the TT genotype with SLE in the same study [12,21].…”

“…SNP rs2205960 (G>T) causes an increase in OX40L expression, which influences the development of SLE disease. Overexpression of OX40L may increase the stimulation of CD4 + T helper effector cells and increase the response of follicular T helper cells whose function is to help B cells proliferate and form antibodies causing inflammation and autoimmunity in specific organs [11][12][13]. The OX40L signaling suppresses the generation and function of interleukin-10 (IL10)-producing CD4 + type 1 regulatory T cells, which play an important role in maintaining peripheral resistance [14].…”

“…According to the meta-analysis conducted by Wang et al (2019), the TT genotype of the TNFSF4 rs2205960 increases the risk of SLE with a significant degree of association [11]. Another study stated that the T allele of TNFSF4 rs2205960 had a significant association in SLE patients from Asian, Caucasian, Hispanic, and Mexican races [10,[12][13][14][15][16][17][18][19].…”

The Impacts of the Clinical and Genetic Factors on Chronic Damage in Caucasian Systemic Lupus Erythematosus Patients

“…On the other hand, renal damage was uncommon in our cohort [6.9%], in contrast to most other studies (14–32.4%) [ 7 , 28 , 29 , 31 , 32 , 33 ], which may be because the expression of renal disease is more aggressive in some ethnic groups (11). Although renal damage was infrequent, it was significantly associated with rs2205960 of TNFSF4 gene, which was previously associated with SLE susceptibility and lupus nephritis (LN) [ 17 , 30 , 36 ].…”

“…The TNFSF4 molecule is a type II transmembrane protein, which is mainly expressed on several activated immune cells. It plays an important role in effector T-cell survival, B-cell differentiation and proliferation, cytokine production and memory cell formation [ 36 ].…”