DRB1*01:01 gene mutation study in the second exon in patients with HIV/AIDS
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1
Riga Stradinš University, Joint Laboratory of Clinical Immunology & Immunogenetic, Latvia
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2
Riga Stradiņš University, Infectology and Dermatology department, Latvia
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3
Riga Eastern Clinical University Hospital, Infectology Center of Latvia, Latvia
Introduction. The human leukocyte antigen (HLA) is the histocompatibility complex in humans and it helps to recognize and present antigens. It has an important role in the formation of the immune system. Many studies related to HIV/AIDS cases demonstrate the protective activity of the DRB1*01:01 allele, namely, AIDS-related complex developed more slowly in patients with this gene in comparison to the patients in which this allele was not detected. However, with the recent developments, this fact became contrary, individuals who would have needed more time to develop AIDS, it developed in less than 6 years. Exactly the second exon forms the binding site for the HLA class II β1 and α1 to the peptide and presents it to the immune system. Any kind of imbalance in the system leads to incorrect or even non-existing immune response. Several functionally important amino acid replacements are connected to missense mutation as a result of which the function of protein changes or completely disappears. In cases of nonsense mutations in which mutation leads to a stop codon, the synthesis of protein is completely stopped and its functional activity disappears. These facts prompted tracing the change of nucleotides in the second exon and to evaluate the impact of such effects on the protective action of the DRB1*01:01 allele.
The aim of the study. Find out whether DRB1*01:01 ongoing point mutations in the second exon affect the operation of this protective alleles in HIV patients.
Materials and methods. The study includes 200 HIV-infected patients. DNA was isolated from venous blood by using the Qiagen QIAamp DNA kit reagents and HLA – the second exon (260 bp) nucleotide sequence was determined by the automatic sequencing – “Big Dye Terminator mix” (Applied Biosystems, USA). Statistical analysis was performed by using Microsoft Excel, DOS StatCalc programs. The significance of the differences in indicators was evaluated according to reliability p0.05. The odds ratio was calculated according to Wolf’s method.
Results. Taking into account the incidence of nucleotide polymorphism in the HLA-DRB1*0101 gene of the second exon, the missense mutations or “hot spots” of this exon were found in 200 analyzed patients: in the 9th codon – 27% of cases, in the 14th codon – 36% of cases; in the 87th codon – 28% of cases (p <0.001). In one sample of a HIV patient, a STOP-codon was found (in the 13th codon). Besides, balanced relationships between nucleotide transversions and transitions have been detected, suggesting mutations in the second exon, and it is known that transversions are very rare in the human genome (OR 0.05, 95% CI 0.00-0.053).
Conclusions. It has been found that amino acid replacement could increase the risk of faster development of HIV than AIDS. After the assessment of the risk and ratio of the protective alleles, it could be possible to determine for each individual which patient is predisposed to faster development of AIDS and this in turn would determine which patient needs to begin the treatment sooner, thus improving the quality of life and prolong survival. For a fuller understanding of the importance of ongoing mutations in the second exon in the development of HIV/AIDS, it is necessary to increase the study group.
Keywords:
HLA,
HIV,
aids,
Mutation,
second exon
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Kasjko
D,
Jasinskis
V,
Eglite
J,
Dobele
E,
Kovalchuka
L,
Sture
G,
Sochnevs
A and
Viksna
L
(2013). DRB1*01:01 gene mutation study in the second exon in patients with HIV/AIDS.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00371
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Received:
18 Mar 2013;
Published Online:
22 Aug 2013.
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Correspondence:
Ms. Diana Kasjko, Riga Stradinš University, Joint Laboratory of Clinical Immunology & Immunogenetic, Riga, Latvia, diana.kasjko@gmail.com