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Vol 43(2009) N 1 p. 55-67;
Zh. M. Kozhekbaeva1 2 3, O.A. Gra1,2, V.S. Fadeev1 I.V. Goldenkova-Pavlova1, I.M. Korsunskaya4, S.A. Bruskin1, E.E. Agafonova4, An.L. Piruzyan4, S.A. Surzhikov2, T.V. Nasedkina2

Association of NAT2 polymorphisms with susceptibility to psoriasis in the Moscow population

1Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 119991, Russia
2Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia
3Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, 33177, USA
4Center of Theoretical Problems of Physical and Chemical Pharmacology, Russian Academy of Sciences, Moscow, 119991, Russia
Received - 2008-05-27; Accepted - 2008-07-17

N-acetyltransferase 2 (NAT2) is a key enzyme of biotransformation phase II that metabolizes genotoxic compounds such as carcinogens and mutagens in different types of cells. A decreased NAT2 activity may correlate with sensitivity to harmful environmental factors, thus increasing susceptibility to different multifactorial diseases, including dermatologic conditions like psoriasis. A biochip developed in our lab to detect 17 NAT2 SNPs was tested on 279 clinical DNA samples from 180 patients with psoriasis and 99 healthy individuals, all residents of Moscow. Six polymorphisms that are most common in European populations (282C > T, 341T > C, 481C > T, 590G > A, 803A > G, and 857G > A) were detected. The NAT2 allele and genotype frequencies for individual SNPs did not differ between patients and healthy individuals. The frequency of the slow acetylation phenotype was increased in patients with type II psoriasis and in normosthenic patients as compared to controls (OR = 1.76, P = 0.177 and OR = 2.07, P = 0.050, respectively). Genotype 341C/C,481T/T,803G/G was significantly more frequent in patients who smoked at least one pack of cigarettes per day and in those who regularly consumed alcohol than in controls (OR = 7.42, P = 0.008 and OR = 106.11, P = 0.003, respectively). The frequency of genotype 341T/T, 481C/C, 590A/-, 803A/A was increased in patients with adverse reactions to medications (OR = 2.05, P = 0.099). Thus, our data suggest that some NAT2 genotypes in combination with certain lifestyles can be considered risk factors of psoriasis in the Moscow population.

Polymorphism, psoriasis, predisposition, acetylation, multiplex PCR, oligonucleotide biochip, diagnostics



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