We investigated the individual and combined effect of functional TNFA −308G/A and IL10 −1082G/A single nucleotide polymorphisms (SNPs) and their genotypes on the susceptibility to systemic lupus erythematosus (SLE) in a Bulgarian population.
Materials and Methods:
Genotyping for −1082A/G IL10 (rs1800896) and −308G/A TNFA (rs1800629) polymorphisms was performed for 154 SLE patients and 224 healthy controls.
Results:
An association between SLE and the rs1800629 polymorphism was established under the allelic model (allele A vs. allele G; odds ratios [OR] = 2.317), the dominant model (GA+AA vs. GG; OR = 3.214), and the overdominant model (GA vs. AA+GG; OR = 3.494). There was no association between rs1800896 and SLE, although a tendency for genetic predisposition to SLE was observed for the IL10 −1082 GG genotype under the recessive genetic model (OR = 1.454). When analyzing the influence of the combined TNFA/IL10 genotypes on SLE occurrence, we found that the carriage of both high cytokine-producing genotypes of two SNPs (TNFA −308AA/GA and IL10 −1082GG) significantly increased the risk of developing SLE with OR of 9.026 (p = 0.006).
Conclusion:
Our findings suggest that the combinatorial complexity of TNFA and IL10 promoter polymorphisms impacts SLE susceptibility. Notably, we found that a TNFA promoter polymorphism is a leading risk factor for SLE susceptibility in a Bulgarian population, while the IL10 −1082 locus appears to act as a significant modifier.
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