Associations between eNOS polymorphisms and susceptibility to systemic lupus erythematosus and rheumatoid arthritis: a meta-analysis

Abstract

Objective. The aim of this study was to determine whether endothelial nitric oxide synthase (eNOS) polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Methods. A meta-analysis was conducted on associations between the 4b/a, T786C, and G894T polymorphisms of eNOS and SLE or RA using the following methods: (1) allele contrast, (2) recessive model, (3) dominant model, and (4) homozygous contrast. Results. Nineteen studies were included in this meta-analysis, comprising eleven studies on SLE (1561 patients and 1565 controls) and eight on RA (1624 patients and 2118 controls). Meta-analysis showed a significant association between SLE and the 4b/a polymorphism using the recessivemodel and the homozygous contrast (odds ratio [OR] = 1.836, 95% confidence interval [CI] = 1.171-2.878, p = 0.008; OR = 2.055, 95% CI = 1.302-3.243, p = 0.002). Ethnicity-specific meta-analysis showed a significant association between the aa vs. bb of the 4b/a polymorphism and SLE in European populations (OR = 2.096, 95% CI = 1.288-4.0, p = 0.027), but not in Arab populations. Stratification by presence of lupus nephritis (LN) indicated a significant association between the a allele and the aa + ab genotype of the 4b/a polymorphismand LN in SLE patients (OR = 2.125, 95% CI = 1.289-3.054, p = 0.003; OR = 2.655, 95% CI = 1.509-4.671, p = 0.001). Meta-analysis indicated no association between SLE and the T786C and G894T polymorphisms. No association was found between the eNOS 4b/a, T786C, and G894T polymorphisms and RA Conclusions. This meta-analysis of published studies shows that the eNOS 4b/a polymorphism may be associated with the development of SLE, but the 4b/a, T786C, and G894T polymorphismsmay be not associated with RA susceptibility.