Citation

Fernández-de-Cossío ME, Cintado A, Nazabal M, Camacho H, Díaz T, et al. (2018) HLA DRB1*/DQA1* Alleles and TNF-alpha G308A Polymorphism Protect against Neuromyelitis Optica in the Cuban Population. J Genet Genome Res 5:040. doi.org/10.23937/2378-3648/1410040

Copyright

© 2018 Hettiaracchchi D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

RESEARCH Article| OPEN ACCESSDOI: 10.23937/2378-3648/1410040

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

Fernández-de-Cossío ME1*#, Cintado A1#, Nazabal M1, Camacho H1, Díaz T1, Villarreal A1, Ale M1, Grass D2, Cervantes-Llanos M1, Pavon-Fuentes N2, Benitez JV1, Cabrera-Gomez JA2, Diaz de la Fe A2 and Pentón-Rol G1

1Biomedical Research Division, Pharmacogenomics Department, Center for Genetic Engineering and Biotechnology, Cuba

2International Center of Neurological Restoration, Cuba

#Equal Contribution.

Abstract

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.