TNF promoter -308 G>A and LTA 252 A>G polymorphisms in Portuguese patients with systemic lupus erythematosus

Abstract

The polymorphism of the tumor necrosis factor (TNF) promoter gene at position -308 and that of the lymphotoxin alpha (LTA) gene at position 252 have been implicated as genetic risk factors for systemic lupus erythematosus (SLE) in some populations. In a nested case-control study, we investigated the possible association of these polymorphisms with susceptibility to SLE and with phenotypic disease features in Portuguese Caucasian patients. TNF-308 G>A and LTA 252 A>G polymorphisms were determined by restriction fragment length polymorphism analysis in a cohort of 115 SLE patients and 152 unrelated healthy controls, and the magnitude of the association between genotypes and SLE diagnosis was calculated. For SLE patients, we also tested the association between disease characteristics and genotypes. No significant differences in genotype or allele frequencies could be identified between SLE cases and controls. Lupus nephritis (OR = 2.84; 95%CI 1.14-7.03, P = 0.02) and the presence of anti-Sm antibodies (OR = 3.11; 95%CI 1.08-8.94; P = 0.03) were significantly more prevalent among lupus patients possessing the TNF-308 A allele. The occurrence of nephritis was also higher in LTA 252 G allele carriers (OR = 2.90; 95%CI 1.12-7.54; P = 0.02). Our results do not support a major role of either the TNF-308 G>A or the LTA 252 A>G polymorphisms as genetic risk factors for SLE. Nevertheless, these polymorphisms appear to associate with the risk of renal lupus and distinct immunological features.

Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans

“…In addition, we found no association with the well-known TNF-308/rs1800869*A, which has been associated with high production of TNFa 39 and clinically with rheumatoid arthritis in Egyptians and Brazilians, 40,41 lupus nephritis in Portuguese individuals 42 and type 1 diabetes in Asians. 43 Both BAT1(intron10)*C and TNF-308*A mark FV16 and the 8.1 ancestral haplotype (HLA-A1, B8, DR3, DQ2).…”

TNF-α − 308 G/A and IFN-γ + 874 A/T gene polymorphisms in Saudi patients with cutaneous leishmaniasis

“…Out of all studied Th1 cytokines, TNFα and IFN-γ were found to be critical for the initiation of preventive immunity against all studied L. species, particularly L. major [10][11][12][13]. TNF-α-308G/A polymorphism was well studied in several autoimmune/inflammatory diseases, the A allele of TNFα (308G/A) was reported to have higher transcriptional activity by 6-7 folds as compared with the common G allele [14,15]. Therefore, the A allele frequency has been implicated in the pathogenesis of several infectious as well as autoimmune disorders [14,15].…”

“…TNF-α-308G/A polymorphism was well studied in several autoimmune/inflammatory diseases, the A allele of TNFα (308G/A) was reported to have higher transcriptional activity by 6-7 folds as compared with the common G allele [14,15]. Therefore, the A allele frequency has been implicated in the pathogenesis of several infectious as well as autoimmune disorders [14,15]. On the other hand, IFN-γ-874 A/T polymorphism was also reported to have a genetic link with several autoimmune/inflammatory disorders through + 874 T allele carriers [16,17].…”

Lymphotoxin-Alpha Gene Polymorphism +252A/G (rs909253, A/G) Is Associated with Susceptibility to Chronic Periodontitis: A Pilot Study

“…These data suggest that the G allele predisposes to periodontal disease. Interestingly, this has also been observed for LT- α (+252 A/G) in other diseases, including rheumatoid arthritis [10], asthma [11], cardiac diseases [12], lupus nephritis [27], breast cancer [28], and chronic Chagas cardiomyopathy [15]. …”