Objective: Systemic lupus erythematosus (SLE) is a multisystem disorder in which defective apoptotic clearance is considered to be an important factor in pathogenesis. DNAse I is associated with disposal of apoptotic nuclear debris. The defective enzyme production due to +2373 A to G (Q222R) in exon 8 is reported to be a genetic risk factor for SLE. SLE in Indians is reported to be severe. There are no genetic studies reported from India which have explored this aspect of DNAseI gene. This study aimed to analyze whether Q222R is a susceptibility factor for SLE and to study its influence on clinical manifestations and autoantibody production in South Indian Tamils.
Method: Three hundred SLE cases (based on ACR 1982 criteria) and 530 age, sex similar and ethnicity matched controls were recruited. All the cases and controls were genotyped for DNAse I Q222R polymorphism using PCR-RFLP method.
Results: DNAse I Q222R polymorphism is prevalent in our population. We observed higher frequency of Q/R in patients compared with controls (60% vs. 53%). This was found to be a genetic risk for SLE susceptibility (p = 0.04, odds ratio 1.5, 95% confidence interval 1-2.1). It also conferred a significant risk for development of nephritis (p = 0.007, odds ratio 1.93, 95% confidence interval 1.2-3.2).
Conclusion: DNAse I Q222R polymorphism is a potential genetic risk factor for SLE in South Indian Tamils. In addition, the mutant allele confers a significant risk for lupus nephritis.
Keywords: ANA; DNAse I; SLE; apoptosis.