THE INFLUENCE OF HUMAN GENETIC FACTORS ON HAART
https://doi.org/10.1234/XXXX-XXXX-2013-2-13-17
Abstract
The review discusses role of human genetic factors in efficiency and complications of highly active antiretrovirus therapy (HAART). Genetic polymorphism of cytochrom P450 and multidrug resistance systems (specifically, CYP2B6 and MDR1/MRP1/P-gp, respectively) affects intracellular concentration of numerous antiretroviral drugs (AD) that may explain differences in clin i cal efficacy of HAART. Genetic background might also impact in rate of miscellaneous complications in patients receiving HAART. Thus hypersensitivity to reverse transcriptase inhibitors has been shown to be dependent on the presence of TNF alpha cytokine gene variant 308A or some alleles of HLA class I (HLA-B*5701,HLA-B*3505, HLA-B*14, HLA-Cw*4, HLA-Cw*8) or class II (HLA-DRB1*0101) loci. Protection from lipodistrophia that represents serious complication of HAART depends on presence of parficu i ar ali eles of polymorphic cytokine genes IL-1, IL-18 and TNF beta. Vice versa, susceptibility to enhanced trigleciride level foli owi ng HAART is associated with polymorphic alleles of APOC3, ARb2, ARb3, HFE, LPIN1 and POLG loci whereas increased risk of neuropathy is associated with genetic variants G516T and C983T of CYP2B6 gene. Various complications like hyperbilirubinemia,neutropenia and astma were found to be associated with UGT1A1*28 that controls small lipophilic molecules, A1203A (rs11568695) of MRP4and HLA-A*68, respectively. Data clearly demonstrates the need in personali zation through genetic profili ng in HAART to increase its efficiency and decrease the rate of complications.
About the Author
A. S. Tumanov
The D.I. Ivanovsky Institute of Virology of The Min istry of Health of The Russian Federation
Russian Federation
Russian Federation
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Review
For citations:
Tumanov A.S. THE INFLUENCE OF HUMAN GENETIC FACTORS ON HAART. Medical Genetics. 2013;12(2):13-17. (In Russ.) https://doi.org/10.1234/XXXX-XXXX-2013-2-13-17
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