Association of allelic variants of genes of detoxification system with clinical presentation of acute intermittent porphyria
Yu. A. Luchinina,
M. V. Goncharova,
V. L. Surin,
T. E. Ivashchenko,
Ya. S. Pustovoyt,
I. V. Karpova,
S. K. Kravchenko https://doi.org/10.18821/0234-5730-2016-61-3-156-160
Abstract
Acute intermittent porphyria (AIP) is caused by the partial deficiency of porphobilinogen deaminase (PBGD), one of the enzymes of the heme biosynthetic pathway. The penetrance of the mutant gene PBGD is not high and averages of 10–15%. Any additional genetic factors, the combination of which with the mutant allele of the PBGD gene leads to the clinical manifestation of AIP is not currently known. The eventual associations of allelic variants of genes of the Phase 1: CYP1A1 (A2455G), CYP2E1 (G1259C) and four genes of the phase 2: NAT2 (C481T, G590A G857A), mEPHX1: Tyr113His – 3rd exon, His139Arg – 4th exon, GSTM1 (Del), GSTT1 (Del) with clinical presentation of AIP were investigated. Homozygous carriership of the “fast” allele of the acetyltransferase gene (genotype N/N) was established to be associated with a latent course of the disease. The combination of “functionally weakened” genotypes of glutathione transferase (class t~) and class M (GSTT10/0, GSTM10/0) can be considered as an unfavorable genetic factor related with the clinical presentation of AIP. Comparative analysis of the frequencies of genotypes and polymorphic alleles of genes CYP1A1, CYP2E1 and mEPHX1 revealed no statistically significant differences between the samples of patients with AIP and asymptomatic carriers of the disease.
Supporting agencies: Russian Foundation of Basic Research (project No 09-04-00456)
About the Authors
Yu. A. Luchinina
National Research Center for Hematology
Russian Federation
Moscow, 125167
Russian Federation
Moscow, 125167
M. V. Goncharova
National Research Center for Hematology
Russian Federation
Moscow, 125167
Russian Federation
Moscow, 125167
V. L. Surin
National Research Center for Hematology
Russian Federation
Russian Federation
Surin Vadim L., senior researcher of the Laboratory of Genetic Engineering
Moscow, 125167
T. E. Ivashchenko
The Research Institute of Obstetrics, Gynecology and Reproductology n.a. D.O. Ott”
Russian Federation
St-Petersburg, 199034
Russian Federation
St-Petersburg, 199034
Ya. S. Pustovoyt
National Research Center for Hematology
Russian Federation
Moscow, 125167
Russian Federation
Moscow, 125167
I. V. Karpova
National Research Center for Hematology
Russian Federation
Moscow, 125167
Russian Federation
Moscow, 125167
S. K. Kravchenko
National Research Center for Hematology
Russian Federation
Moscow, 125167
Russian Federation
Moscow, 125167
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Review
For citations:
Luchinina Yu.A., Goncharova M.V., Surin V.L., Ivashchenko T.E., Pustovoyt Ya.S., Karpova I.V., Kravchenko S.K. Association of allelic variants of genes of detoxification system with clinical presentation of acute intermittent porphyria. Russian journal of hematology and transfusiology. 2016;61(3):156-160. (In Russ.) https://doi.org/10.18821/0234-5730-2016-61-3-156-160
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