You are using an outdated browser. For a faster, safer browsing experience, upgrade for free today.

MOLECULAR GENETIC STUDIES OF RISK ASSESSMENT IN DEVELOPING OCCUPATIONAL ALLERGIC DERMATOSES

1(38) 2014

DOI xxxxxxxx

Kuzmina L. P., Izmerova N. I., Kolyaskina M. M., Lazarashvili N. A., Petinati Y. A.

MOLECULAR GENETIC STUDIES OF RISK ASSESSMENT IN DEVELOPING OCCUPATIONAL ALLERGIC DERMATOSES

Federal State Budgetary Institution Research Institute of Occupational Health of the Russian Academy of Medical Sciences, Moscow, Russian Federation

Full article (PDF), RUS

Purpose of work. To examine the role of polymorphic variants of genes of the system of xenobiotic biotransformation in mechanisms of formation and development of occupational allergic dermatoses .
Methods of research. The study included 201 workers, contacted with sensitizing and iritative substances with the established ooccupational allergic dermatoses. Gene polymorphisms of cytochrome P-450: cytochrome P-450 1A1 (CYP1A1 (* 2C I462V (A> G)), and cytochrome P-450 3A4 (CYP3A4 (*1B A> G), glutathione-S-transferase M1 (GSTM1 gene), glutathi- one-S-transferase T1 (GSTT1 gene), microsomal epoxidehydrolase 1 (ERNH1 of polymorphisms H139R (A-415G) and Y113H (T-337C) were used in order to assess mechanisms of formation and development of occupational allergic dermatoses by the method of polymerase chain reaction (PCR) and pyrosequencing reaction.
Results. The study of polymorphic genes of xenobiotic biotransformation system in patients with occupational allergic derma¬toses showed significantly higher percentage of polymorphic variants of genes CYP 1A1*2C and EPHX1 A-415G as compared with the population control. The combination of 3 or more adverse hetero-and homozygous alleles CYP 1A1, CYP3A4, ERNH1 and deletions of genes GSTM1 and GSTT1 are characterized by earlier development (after working in hazardous conditions up to 5 years) of severe courses and unfavorable prognosis for occupational skin diseases.
Conclusions. The obtained results can make the basis for development of personalized treatment and preventive measures with the use of antioxidant therapy in individuals, working in allergo-hazard productions and in patients with occupational allergic dermatoses.


Key words: genes of biotransformation, occupational allergodermatosis, risk assessment

References

  1. Kuzmina, L. P., Bezrukavnikova, L. M. et al. 2005, «Molecular mechanisms and individual-specific metabolism, determining the occurrence, clinical course and outcome of professional and work-related diseases». Actual problems of "Occupational medicine". Collection of papers. (Ed. N. Izmerov), Moscow, pp. 465-478 (in Russian).
  2. Spitsin, V. A. 2008, Ecological genetics of human. Moscow: Science, 503 p. (in Russian).
  3. Izmerova, N. I., Ivanova, L. A. 1989, Clinical aspects and laboratory diagnosis of early manifestations of occupational dermatoses and their prevention. Collection of papers: Problems prenosological diagnostics, pp. 280-281 (in Russian).
  4. Gonzalez, D. H., Bonnard, G., Grienenberger, J.-M. 1993, A gene involved in the biogenesis of c-typecytochromes is co-transcribed with a ribosomal protein gene in wheat mitochondria. Current Genetics, no. 21, pp. 248-255.
  5. Sipes, I. G., Gandolfi, A. J. 1986, Biotransformation of toxicants. Casarett and Doull's toxicology. N. Y.: Macmillan Publishing Company, pp. 99-173.
  6. KuKes, V. G., Gratsev, S. B., et al. 2008, Metabolism of drugs. Scientific bases of the personaized medicine: a guide for physicians. M.: Geotar-Media, 304 p. (in Russian).
  7. Kuzmina, L. P., Izmerova, N. I., 2006, The Encyclopedia on occupational medicine. (Ed. N. Izmerov) (in Russian).
  8. Westphal, G. A., Reich, K., Schulz, T G, et al. 2000, «N-acetyltransferase 1 and 2 polymorphisms in para- substituted arylamine-induced contact allergy», British Journal Dermatologic, no. 142, pp.1121-1127.