HLA DRB1*/DQA1*Alleles and TNF-alpha G308A Polymorphism Protect against Neuromyelitis Optica in the Cuban Population

Background: Neuromyelitis optica (NMO) is a complex immune-mediated disease whose prevalence differs among ethnic groups, most likely due to genetic factors. The presence of the Human Leucocyte Antigens (HLA) extended haplotype is a risk for NMO. The tumor necrosis factor-alpha (TNF-a) is believed to play a role in NMO pathogenesis. Although single nucleotide polymorphisms (SNPs) in the TNF-a promoter region (pTNF-a) has been shown to influence levels of TNF-a production, such an association is not evident in the Cuban population. The aim of this study was to examine the association between the HLA alleles, pTNF-a SNPs, the amount of the TNF-a protein, and the clinical parameters of a sample of NMO patients from the Cuban population. Methods: 20 patients diagnosed with relapsing NMO (R-NMO), and 100 unrelated healthy controls, were evaluated. Ancestry was determined and an HLA typing case-control association study was carried out. Genomic DNA was extracted from peripheral blood leucocytes. HLA DRB1 and DQ alleles typing were determined by SSP-PCR. The DNA sequence approach was used to evaluate pTNF-a SNPs. The TNF-a protein expression was measured by ELISA. Results: Genetic ancestry estimates showed that in NMO patients the European contribution prevailed. No association of HLA alleles to NMO susceptibility was observed, although there was a slight protective effect of HLA DQA*03, DRB1*10 followed by DRB1*11 alleles. An association was found between the pTNF-a 308 G/A and a possible protective role against NMO (OR = 0.37, p values p < 0.001). The TNF-a protein did not differ between NMO patients and controls. Moreover, the association of HLA alleles and SNPs was not statistically significant when the clinical parameter were evaluated. Conclusion: Our results showed that in this sample of Cuban NMO patients HLA alleles as well as pTNF-a SNPs differ from other populations. There was no association between HLA alleles, pTNF-a SNPs and clinical variables.