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

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 recessive model 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 polymorphism and 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 polymorphisms may be not associated with RA susceptibility.