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

Aims: To find out whether ongoing missense mutations in the exon 2 of DRB1*01:01 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 *01:01 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.