ABSTRACT
Background & objectives: Interleukin-1 (IL-1) is one of the pro-inflammatory cytokines that plays a main role in the regulation of immune and inflammatory responses. Interleukin 4 (IL-4) as an anti-inflammatory cytokine regulates balance between Th1 and Th2 immune responses. This study was undertaken to investigate the IL-1β and IL-4 genes polymorphisms in patients with systemic lupus erythematosus (SLE) and also association between the polymorphisms and susceptibility to SLE. Methods: One hundred and sixty three SLE patients and 180 healthy controls were genotyped for the IL-4 VNTR (variable number tandem repeat), IL-1β C-511T and IL-1β T-31C polymorphisms by polymerase chain reaction (PCR) or PCR-RFLP (restriction fragment length polymorphism) method. Results: The frequencies of CC genotype and C allele of the IL-1β T-31C polymorphism were significantly (P<0.01) lower in SLE patients than controls. Moreover, the frequencies of RP1/RP2 genotype and RP2 allele of IL-4 VNTR polymorphism were significantly (P<0.05) higher in the SLE patients. No association was observed between IL-1β C-511T polymorphism and increased risk of SLE. We observed increased frequency of CT and TT genotypes of IL-1β C-511T polymorphism in SLE patients with malar rash compared to SLE patients without this manifestation. Interpretation & conclusions: The present findings suggest that IL-1β T-31C and IL-4 VNTR polymorphisms but not IL-1β C-511T polymorphism may contribute in SLE pathogenesis. In addition, CT and TT genotypes of IL-1β C-511T polymorphism were associated with SLE.
ABSTRACT
INTRODUÇÃO: Recentemente, relatou-se uma associação entre artrite reumatoide (AR) e a variante rs7700944 G>A nos domínios imunoglobulina e mucina de células T (TIM-4). OBJETIVO: Investigar o impacto desse polimorfismo na suscetibilidade a AR em uma amostra da população iraniana. PACIENTES E MÉTODOS: Este estudo caso-controle foi conduzido em 120 pacientes com AR e 120 indivíduos saudáveis. O polimorfismo rs7700944 do gene TIM-4 foi determinado usando-se o ensaio tetra amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR). RESULTADOS: Não se observou diferença significativa quanto ao polimorfismo rs7700944 do gene TIM-4 entre os pacientes com AR e os indivíduos saudáveis. Nas mulheres, não houve associação significativa quanto ao polimorfismo rs7700944 do gene TIM-4 nos dois grupos. Nos homens, o genótipo GA+AA, em comparação ao GG, aumentou o risco para AR (OR = 5,15; IC 95% = 1,30-20,48; P = 0,020). Além disso, os resultados mostraram que o alelo rs7700944 A aumentou o risco para AR (OR = 4,39; IC 95% = 1,43-13,54; P = 0,009). CONCLUSÃO: Nossos resultados não confirmam a existência de associação entre AR e o polimorfismo rs7700944 do gene TIM-4. Uma interação entre esse polimorfismo e sexo sugere uma associação sexo-específica entre AR e esse polimorfismo de nucleotídeo único, que ainda requer elucidação.
INTRODUCTION: Recently, an association between rheumatoid arthritis (RA) and the rs7700944 G>A variant in the T-cell immunoglobulin and mucin domains 4 (TIM-4) has been reported. OBJECTIVE: The present study aimed at investigating the impact of that polymorphism on susceptibility to RA in a sample of the Iranian population. Patients and methods: This case-control study was conducted on 120 patients with RA and 120 healthy subjects. The rs7700944 polymorphism in the TIM-4 gene was determined using tetra amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) assay. RESULTS: No significant difference was observed regarding the rs7700944 polymorphism of the TIM-4 gene between patients with RA and normal individuals. In females, no significant association was found between the groups concerning the rs7700944 polymorphism of the TIM-4 gene. In males, the GA+AA genotype increased the risk of RA in comparison with the GG genotype (OR = 5.15, 95% CI = 1.30-20.48, P = 0.020). Furthermore the results showed that the rs7700944 A allele increased the risk of RA (OR = 4.39, 95% CI = 1.43-13.54, P = 0.009). CONCLUSION: Our results do not support an association between the rs7700944 polymorphism of the TIM-4 gene and RA. An interaction between this polymorphism and sex suggests a sex-specific association between this single nucleotide polymorphism and RA, which remains to be fully elucidated.