[Association study of the Val158Met polymorphism of the catechol-O-methyltransferase gene and alcoholism and heroin dependence: the role of a family history].

The aim of this study was to investigate the association the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene and predisposition to alcoholism and heroin dependence. The authors genotyped DNA samples from 964 Russian males (395 alcoholics, 243 heroin addicts and 326 healthy controls). The association between the Val158Met COMT polymorphism and alcoholism was found in males with high density of family history (two or more blood relatives with alcoholism within the family). In this group, the frequency of a L (Met) allele was significantly higher in comparison with controls (p=0,001), patients without family history (p=0,034) and patients with the mild density of family history (p=0,0005). The frequency of the HH (ValVal) genotype was reduced as well compared to the controls (p=0,003). In the group of heroin addicts with the mild density of family history, there was a trend to lower frequency of the HH genotype (p=0,058) compared to patients without family history. The results suggest that the functional Val158Met COMT polymorphism is one of the significant markers of genetic predisposition to addiction diseases.

[Identification of mutations in the arylsulfatase B gene in Russian mucopolysaccharidosis type VI patients]. / Identifikatsiia mutatsii v gene arilsul'fatazy B u Rossiiskikh bol'nykh s mukopolisakharidozom tipa VI.

Molecular genetic analysis of the gene for arylsulfatase B (ASB) was conducted in ten Russian patients with type VI mucopolysaccharidosis (MPS VI) of different severity. Eight exons from the translated region of the ASB gene of each patient were amplified and sequenced using the nonradioactive method. Fourteen mutant alleles were identified in the sample studied by means of DNA analysis; 13 of them had not been described before. All patients except for one, who was an offspring of a consanguineous marriage, were genetic compounds with respect to the mutations found. Polymorphic sites A/G 1072 and A/G 1126, which were earlier revealed in exon 5 of the ASB gene, were found in five out of ten patients studied. The spectrum of mutant alleles of the ASB gene was highly specific and agreed with the characteristics of the population genetic load.

[Program for diagnosis and prevention of inherited metabolic diseases of cellular organelles]. / Prgramma diagnostiki i profilaktiki nasledstvennykh boleznei obmena kletochnykh organell.

A programme for diagnosis and prevention of lysosomal, peroxisomal, and mitochondrial [respiratory chain diseases (RCD)] diseases was developed on clinical, biochemical, and molecular approaches. The authors made postnatal diagnosis was made in 674 patients from 516 families and prenatal diagnosis in 124 fetuses in 94 families at risk. DNA analysis of mutant alleles in the mucopolysaccharidoses (MPS) I, II, and VI revealed 14, 13, and 4 new mutant alleles in IDS, ASB, IDUA genes, respectively. The pressure of a mutation process played a major role in the distribution of mutant alleles leading to MPS I and VI, but along with this factor genetic drift and migration undoubtedly influenced the observed spectrum of IDUA alleles in Russia. A clinical phenotype of patients with different MPS was analyzed on the basis of uniform registration of 167 symptoms and signs in 249 patients. Special statistical approaches were developed to characterize early manifestations of different MPS and "unique" signs and symptoms for many of them and "phenotypic distances" between them. The similar problems were solved for RCD through uniform registration of 110 symptoms and signs in 54 patients with different syndromes: pathognomonic symptoms for the whole RCD and "unique" symptoms for syndromes were defined.

[A PCR-system of analyzing polymorphic markers in gamma-A and gamma-G globin genes and gene for human blood coagulation factor IX with an internal control of the completeness of restriction hydrolysis]. / PTsR-sistemy analiza polimorfnykh markerov v gamma-A i gamma-G globinovykh genakh i gene faktora koaguliatsii krovi IX cheloveka s vnutrennim kontrolem polnoty restriktsionnogo gidroliza.

New systems are proposed for the PCR analysis of HindIII polymorphic sites in the gamma A and gamma G globin genes and of TaqI polymorphic site in the human factor IX gene of blood population. DNA fragments amplified according to the systems described contain constant restriction site of the appropriate endonuclease, in addition to the polymorphic one, which significantly improves the reliability of the RELP analysis. The systems proposed are highly specific and may be used for DNA diagnosis of beta-thalassemia and haemophilia B.