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AB0012 TNF-Alpha and IL-10 Promoter Polymorphisms in Susceptibility To Systemic Lupus Erythematosus in Bulgarian Population
  1. M. Ivanova Goycheva1,
  2. S. Stanilova2,
  3. R. Stoilov1,
  4. R. Rashkov1,
  5. I. Manolova3
  1. 1Clinic of Rheumatology, University Hospital “St. Iv. Rilski”, Sofia
  2. 2Department of Molecular Biology, Immunology and Medical Genetics
  3. 3Department of Health Care, Medical Faculty, Trakia University, Stara Zagora, Bulgaria

Abstract

Background Cytokine network alterations contribute strongly to the initiation and perpetuation of systemic lupus erythematosus (SLE). The production of IL-10 and TNF-alpha, which are important regulators of inflammation is under genetic control and functional significance of a number of single nucleotide polymorphisms (SNPs) in the regulatory regions of IL10 and TNFA genes has been demonstrated 1,2.

Objectives In the present study, we analyzed the involvement of two functional SNPs in the promoter region of IL-10 (-1082 A/G; rs1800896) and TNF-alpha (-308 G/A, rs1800629) genes in the susceptibility to SLE in Bulgarian population.

Methods A case–control study was carried out on 154 SLE patients and 152 sex and age matched healthy subjects. The allele and genotype frequencies of rs1800896 and rs1800629 were determined using allele specific PCR and restriction fragment length RFLP-PCR assays, respectively.

Results We observed significant differences in the genotype (p=0.001) and allele (p=0.002) frequencies of TNFA -308G/A SNP between SLE patients and controls. There was an increase of the TNFA -308 A allele (21.8% vs 12.5%; OR =1.95) and a higher frequency of heterozygous AG genotype (42.2% vs 22.4%; OR =2.52) in cases compared to controls (p<0.001). Logistic regression analysis revealed that the presence of TNFA -308 A allele in the genotype (AG+AA) was associated with 2.4 times higher risk of developing SLE (OR=2.417; p<0.001). Regarding the distribution of IL10 -1082 A/G polymorphism a higher frequency of IL10 -1082 G allele (40.9% vs. 33.9%; OR =1.36; p=0.072) and GG genotype (17.5% vs. 9.2%; OR =2.09; p=0.033) was observed in SLE patients compared to controls. When analyzing the influence of combined IL10/TNFA genotypes on SLE appearance, we found that the carriage of both high cytokine producing genotypes of two polymorphisms (IL10 -1082 GG and TNFA -308 AA/GA, respectively) significantly increased the risk of developing SLE with OR =7.94; p=0.006.

Conclusions Our results suggest that combination of IL10-1082A/G and TNFA -308G/A polymorphisms strongly contribute to the SLE susceptibility in Bulgarian population, particularly due to their functional effect on inducible cytokine production. Carriage of each of the genotype associated with high production of IL-10 and TNFA independently lead to 2-fold higher risk of developing SLE, while combining them increases the risk up to 8 times.

References

  1. Wesdendorp RG et al. Lancet 1997;349:170-3.

  2. Eskdale J. et al. Immunogenetics 1997; 46:120-128.

Disclosure of Interest None declared

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