[Association of NAT2 polymorphism with risks to develop psoriasis and various dermatological diseases in Moscow population].

Ruacetyltransferase 2 (NAT2) is one of key enzymes of the second phase of biotransformation that metabolize genotoxic compounds such as carcinogens and mutagens in different types of cells. There is a correlation between the decreasing activity of NAT2 gene product and the sensitivity to harmful environmental factors that increase the risk of occurrence of different multifactorial diseases, including dermatological ones like psoriasis. We developed the NAT2-biochip for 17 SNPs. The biochip was been tested on 279 clinical DNA samples from 180 patients with psoriasis and 99 healthy individuals, residents of Moscow. We found only six SNPs that were significant for European populations (282C > T, 341T > C, 481C > T, 590G > A, 803A > G and 857G > A). The analysis in psoriasis group did not show any genotype association. The increase in frequency of a slow acetylation phenotype in group of patients with type II psoriasis and in group of patients with normosthenic constitution, in comparison with control group (OR = 1.76,p = 0.177 and OR = 2.07,p = 0.050, respectively) has been revealed. The results for patients smoking one or more pack of cigarettes per day, and daily alcohol drinking in comparison with the control showed an increase in frequency for the genotype 341C/C, 481T/T, 803G/G (OR = 7.42, p = 0.008 and OR = 106.11, p = 0.003, respectively). We also found an increase of frequency of genotype 341T/T, 481C/C, 590A/-, 803A/A in patients with side reactions to medical products comparing with group of healthy donors (OR = 2.05, p = 0.099). Thus, the present data show that the certain NAT2 genotypes and some styles of life can be considered as risk factors of psoriasis development in this muscovite population.

[Identification of functionally significant mutations in NAT2 gene using biological microchips].

The product of gene NAT2 (N-acetyltransferase 2) is involved in the biotransformation system and participates in detoxication of some arylamine derivatives (in particular 2-aminofluorene, 4-aminobiphenyl and 4-naphthylamine) which are strongly mutagenic and carcinogenic. It also renders toxicological and pharmacological influence on a metabolism of medical products metabolized by the enzyme. We developed a microchip for detection of 16 functionally significant mutations coding 36 alleles of gene NAT2. Combinations of these alleles allow us to reveal more than 660 genotypes, which can be divided into four groups according acetylation phenotype: "fast" (R/R), "intermediate" (R/S), "slow" (S/S) and group with average or slow acetylating (R/S or S/S) alleles. The groups "R/S or S/S" include alleles, formed by a combination of 7 mutations (191G/A, 282C/T, 341T/C, 481C/T, 590G/A, 803A/G, 857G/A), theirs cis-trans position can be revealed by restriction analysis. In 37 of 71 DNA samples we unequivocally defined NAT2-genotypes, and other 34 samples have been characterized by more than two genotypes. 16 samples out of 34 had acetylation phenotype of group "R/S or S/S", which is characterized by the following combination of mutations: 282C/T, 341T/C, 481C/T, 590G/A and 803A/G. Thus, the developed biochip is a convenient screening method for primary detection of the majority of polymorphic replacements in gene NAT2.

[Population analysis and determination of the ethnic background are necessary in the study of multifactorial diseases: a study using the Dagestan population as a model].

Psoriasis, a multifactorial disease with genetic predisposition, has been used as an example to study the role of the ethnic background in multifactorial diseases in the Dagestan population. The individual information card (IIC) is proposed as the main tool for correct collection and processing of information. The results of the study demonstrate that the Dagestan population is a convenient and adequate model population for studying multifactorial diseases, such as psoriasis, and may serve as an object for studying the role of heredity in the etiologies and pathogeneses of this and other multifactorial diseases.

[The molecular genetics of psoriasis].

The review is dedicated to molecular-and-genetic aspects of psoriasis. The paper contains a general characterization of this skin disease and a range of hypotheses concerning its appearance, clinical manifestations, and maintenance. Its autoimmune nature with the central role played by T-cells is considered to be the basic theory of the appearance of psoriasis. According to the results of analysis of experimental data on psoriasis genetics, including family background, psoriasis is defined as a complex multigene multifactor disease, whose manifestations are determined by a combination of certain genes as well as by various environmental trigger factors. The authors consider ethnic features of psoriasis, and genes that determine predisposition to the disease. Prospects of the search of predisposition genes, including analysis of the polymorphism of unit nucleotides, are outlined in the article.

[Genetic markers and psoriasis in three ethnic populations of Dagestan].

Analysis of clinical material obtained from the individuals (49 psoriasis patients and 357 individuals without this disease) representing three ethnic populations of Dagestan (Avars, Dargins, and Kumyks) was performed. Polymorphism of the blood group loci AB0, Rhesus (RH), Kell, P, and Lewis, as well as of the protein-encoding loci for haptoglobin (HP), group-specific component (GC), and the enzymes, including glycosylase (GL01), esterase D (ESD), 6-phosphate dehydrogenase (6PDG), and acid phosphatase (ACP), was studied. It was demonstrated that in the pooled sample of Avars and Kumyks the Lewis system phenotype Le(a-b-) and the RH homozygotes (ee/ee) were statistically significantly more frequent among the psoriasis patients (P = 0.0488 and P = 0.0166, respectively), than among healthy controls of the same ethnic groups. It was suggested that for the pooled sample of Avars and Kumyks, homozygosity for the recessive RH allele (ee/ee) in combination with the Le(a-b-) phenotype, representing homozygosity for recessive allele le, was the risk factor for the development of psoriasis.