Polymorphic variants of antioxidative defense enzymes and their gene-gene epistatic interactions in systemic lupus erythematode patients.

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which pathogenesis oxidative stress has an important role. Single nucleotide polymorphisms (SNPs) in the genes that code enzymes involved in the antioxidative defense are possible factors that are responsible for their decreased activity of antioxidative defense enzymes. Thus, the aim of the study was to examine association of SNPs in these genes with SLE. A total of176 subjects were involved in this study. CAT A-21T (rs7943316), CAT C-262T (rs1001139) and manganese SOD (MnSOD) Ala16Val (rs4880) SNPs were determined using PCR-RFLP method, while GSTT1 and GSTM1 were determined using multiplex PCR. The obtained results showed significant differences in the distribution of genotypes (df=2; p=0.001) and alleles (p<0.001; OR=2.227; 95% CI=1.429-3.741) of rs4880 between patients and controls. MnSODValVal genotype showed association with neurologic manifestations (p=0.016; OR=6.7; 95% CI=1.18-37.89), while homozygous GSTT1 showed association with musculoskeletal manifestations of SLE (p=0.008; OR=4.168; 95% CI=1.364-12.737). AlaVal/T+M+ genotype combination is a high-risk genotype for SLE. SNP-SNP interaction model showed positive correlation between CAT A-21T and CAT C-262T SNPs in SLE patients which was not influenced by the linkage disequilibrium (r 2=0.005; D'=0.071). MnSODVal allele is a risk factor for SLE, as well as for SLE with neurologic manifestations, while homozygous GSTT1 genotype is a risk factor for SLE with musculoskeletal manifestations. Catalase SNPs (C-262T and A-21T) show positive correlation in the model of SNP-SNP interaction.