Mutations in HLA DRB1*0101 Exon 2 in a Sub-population of Latvia.

ABSTRACT

Aims: To find out whether ongoing missense mutations in the exon 2 of DRB1*0101 affect the operation of this protective allele in HIV patients. Place and Duration of Study the Clinical Immunology and Immunogenetics Laboratory of Riga Stradiņš University, Riga Eastern Clinical University Hospital, “Infectology Center of Latvia”, between May 2006 and December 2011. Methodology: The study includes 200 HIV-infected patients. DNA was isolated from venous blood samples using the Qiagen QIAamp DNA kit reagents and the exon 2 nucleotide sequence of HLA was determined by the automatic sequencing – “Big Dye Terminator mix” (Applied Biosystems, USA). Statistical analysis was performed using Microsoft Excel, DOS StatCalc programs. The significance of the differences in indicators was evaluated according to reliability p£0.05. The odds ratio was calculated according to Wolf’s method. Results: We found missense at codon 47– in 80% of cases; at codon 67– in 20% of cases; at codon 75 – in 11% of cases; at codon 82– in 10% of cases; at codon 86– in 10% of cases (p<0.05) (See Table 3). One of the HIV patients had a STOP-codon (codon 13). Besides, a balance between nucleotide transversion and transition has been observed, suggesting mutations in the exon 2 (transversion in a human genome is rare) (OR 0.05, 95% CI 0.00-0.053). Conclusion: The results of the study are not complete in order to be able to say conclusively that the existing mutations in the exon 2 of HLA-DRB1 *0101 gene cause wrong immune response, thus the protective functions of this allele are not fulfilled. For a fuller understanding of the importance of ongoing mutations in the exon 2 in the development of HIV/AIDS, it is necessary to increase the study group.