Polymorphism of the genes for antioxidant defense enzymes and their association with the development of chronic obstructive pulmonary disease in the population of Bashkortostan

In this study, frequencies of the polymorphic variants of the genes encoding antioxidant enzymes, GSTM1, GSTT1, GSTP1, CAT, GPX1, NQO1, SOD1, and SOD3 were examined in three ethnic groups of healthy subjects from the Republic of Bashkortostan (Russians, Tatars, and Bashkirs). An association of these markers with the development of chronic obstructive pulmonary disease (COPD) was tested. Interethnic differences relative to the distribution of the polymorphic variants of the GSTP1 locus Ile105Val and the NQO1 locus 609C/T were revealed. Relative to the genotype distribution at the Ile105Val locus of the GSTP1 gene, ethnic group of Bashkirs was found to be statistically significantly different from Tatars (χ² = 8.819; d.f. = 2; P = 0.012). Relative to the genotype frequency distribution pattern at the NQO1 locus 609C/T, the group of Bashkirs differed from Russians (χ² = 8.913; d.f. = 2; P = 0.012). An association of genotype Val/Val of the GSTP1 Ile105Val locus with the risk of COPD in Russians (χ² = 5.25; P = 0.022; P _cor = 0.044; OR = 4.09), and of the GSTP1 haplotype *D in Tatars, was demonstrated (χ² = 11.575; P = 0.0014; P _cor = 0.0042; OR = 3.178). Genotype TT of the CAT ?262C/T locus marked resistance to the COPD development in Russians (χ² = 6.82; P = 0.0098; P _cor = 0.0196; OR = 0.31; 95%CI, 0.119 to 0.77). The risk for COPD in the ethnic group of Tatars was associated with the CAT haplotype (?262)C/(1167)T (χ² = 6.038; P = 0.0147; P _cor = 0.044; OR = 1.71). Analysis of the NQO1 haplotypes at the 465C/T and 609C/T loci showed that haplotype 465C/609T was associated with COPD in Russians (χ² = 4.571; P = 0.0328; P _cor = 0.01; OR = 1.799). It was demonstrated that Gly allele of the Arg213Gly polymorphic locus of the SOD3 gene marked the risk for COPD in the ethnic group of Tatars (OR = 2.23; 95%CI, 1.22 to 4.1). Thus, GSTP1, CAT, NQO1, and SOD3 polymorphisms play an important role in the development of COPD among the population of Bashkortostan.     

Frequencies of <Emphasis Type="Italic">CYP1B1</Emphasis> and <Emphasis Type="Italic">CYP2F1</Emphasis> polymorphic variants in three ethnic groups of Bashkortostan and in patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a multifactorial respiratory disorder. Members of the cytochrome P450 family catalyze oxidative metabolism of exogenous chemicals and activate their substrates into reactive intermediates that may initiate lung injury. The frequencies of CYP1B1 and CYP2F1 polymorphic markers were determined in healthy people from Bashkortostan and tested for association with COPD. Using PCR-RFLP, the polymorphic markers Leu432Val (CYP1B1) and c.14-15insC (CYP2F1) were studied in healthy Russians (N = 191), Tatars (N = 198), and Bashkirs (N = 78) and in Russian (N = 169) and Tatar (N = 137) COPD patients. The CYP2F1 genotype frequency distribution proved to differ between the three ethnic groups (χ 2 = 21.29, d.f. = 4, P = 0.0001), Tatars having a higher frequency of the c.14-15insC/c.14-15insC genotype (6.38%). The highest frequency (39.74%) of the heterozygous genotype was observed in Bashkirs. The frequency of the insertion-free CYP2F1 variant in Tatars with extremely severe COPD and onset after 55 years of age was significantly higher (87.5%) than in patients of the same age group with moderate or severe COPD (87.50% vs. 75.53%, χ 2 = 3.964, d.f. = 1, P = 0.046; OR = 2.268). The allele and genotype frequency distributions of the CYP1B1 Leu432Val polymorphism were similar in the Russian, Tatar, and Bashkir ethnic groups. Leu432Val of CYP1B1 was not associated with COPD.     

Synthesis of Four Stereoisomers of Carbocyclic 5′-NOR D4A and Evaluation of Their Triphosphates as Substrates for DNA Polymerases

Abstract

A method was developed for synthesis of the four stereoisomeric enantiomerically pure 5′-nor carbocyclic nucleosides 4b, ent-4b, 10 and ent-10 starting from the common enantiomerically pure allylic monoacetate 1. Nucleoside analogues were converted to the corresponding triphosphate derivatives 6, ent-6, 12, and ent-12. The substrate properties of the latters towards different DNA polymerases were evaluated.     

Association of cytokines genes (ILL, IL1RN, TNF, LTA, IL6, IL8, IL0) polymorphic markers with chronic obstructive pulmonary disease

The purpose of this study was to investigate the possible roles of the cytokines genes in the development of chronic obstructive pulmonary disease (COPD). Polymorphisms in the genes encoding IL1B, IL1RN, TNFA, LTA, IL6, IL8 H IL10 were investigated in COPD patients (N = 319) and healthy individuals (N = 403) living in Ufa, the Republic of Bashkortostan. We observed that IL1RN*2/IL1RN*2 genotype of ILRN gene was associated with susceptibility for COPD (9.8% vs. 4.67%; chi(2)= 5.45, df= 1, P = 0.02; OR = 2.21). Analysis of the LTA gene polymorphic locus A252G showed that in patients with COPD, the frequency of the GG genotype was significantly higher than that in the control group (7.84% vs. 3.72%; chi(2) = 5.00, df= 1, P = 0.025). The increase of this genotype was significant in case of stage IV of COPD (11.18% vs. 4.79%; chi(2) = 3.075, df= 1, P = 0.07). Frequency of genotype combination TNFA-308 G/G and LTA252 A/A significantly decreased in COPD group (38.55% vs. 46.93% in control group; chi(2) = 8.82, df= 1, P = 0.0039). The frequency of GG genotype of the IL6 gene was higher in the patients with stage IV of COPD (43.75% vs. 31.54%, chi(2) = 4.14, P = 0.041). Our results indicate that the genotype frequency of the T(-511)C, T3953C of IL1B, G(-308)A of TNFA, G(-1 74)C of IL6, A(-251)C of IL8 and C(-627)A of ILl0 genes polymorphisms was similar in COPD and healthy control groups.     

Larvae of related Diptera species from thermally contrasting habitats exhibit continuous up-regulation of heat shock proteins and high thermotolerance

A population of Stratiomys japonica, a species belonging to the family Stratiomyidae (Diptera), common name ‘soldier flies’, occurs in a hot volcanic spring, which is apparently among the most inhospitable environments for animals because of chemical and thermal conditions. Larvae of this species, which naturally often experience temperatures more than 40 °C, have constitutively high concentrations of the normally inducible heat-shock protein Hsp70, but very low level of corresponding mRNA. Larvae of three other species of the same family, Stratiomys singularior, Nemotelus bipunctatus and Oxycera pardalina, are confined to different type semi-aquatic habitats with contrasting thermal regime. However, all of them shared the same pattern of Hsp70 expression. Interestingly, heat-shock treatment of S. japonica larvae activates heat-shock factor and significantly induces Hsp70 synthesis, whereas larvae of O. pardalina, a species from constant cold environment, produce significantly less Hsp70 in response to heat shock. Adults of the four species also exhibit lower, but detectable levels of Hsp70 without heat shock. Larvae of all species studied have very high tolerance to temperature stress in comparison with other Diptera species investigated, probably representing an inherent adaptive feature of all Stratiomyidae enabling successful colonization of highly variable and extreme habitats.     

Polymorphic markers of the CYP1B1 (4326C > G), CYP2F1 (c.14_15insC), CYP2J2 (-76G > T), and CYP2S1 (13106C > T and 13255A > G) genes and genetic predisposition to chronic respiratory diseases induced by smoking and occupational factors

The contribution of the polymorphic markers of cytochrome P450 genes to respiratory diseases caused by smoking and occupational factors has been assessed. For this purpose, PCR-RFLP analysis of the CYP1B1 (rs1056836, 4326C > G), CYP2F1 (rs11399890, c.14_15insC), CYP2J2 (rs890293, -76G > T), and CYP2S1 (rs34971233, 13106C > T and rs338583, 13255A > G) gene polymorphisms has been performed. The analysis has shown that the polymorphic variants of the CYP1B1 (rs1056836, 4326C > G) and CYP2F1 (rs11399890, c. 14_15insC) genes may contribute to the development of occupational chronic bronchitis. The proportion of CYP1B1* 1*3 heterozygotes in the group of patients with occupational chronic bronchitis is considerably greater than in the group of healthy workers (69.16% versus 53.29%; chi2 = 5.94, P = 0.02, P(cor) = 0.04, OR = 1.97, the 95% CI is 1.13-3.42). Patients with occupational chronic bronchitis and healthy workers significantly differed from each other in the frequency distribution of the genotypes ofthe CYP2F1 (rs11399890, c.14_15insC) polymorphic marker (chi2 = 6.18, d.f = 2, P = 0.05). The frequency of the wild type/ins heterozygous genotype for the CYP2F1 gene is higher in healthy workers (36.08%) than in patients (22.22%) (chi2 = 5.48, P = 0.02, P(cor) = 0.04, OR = 0.51, the 95% CI is 0.28-0.90). No association has been found between the CYP2J2 (rs890293, -76G > T) or CYP2S1 (rs34971233, 13106C > T, P466L and rs338583, 13255A > G) gene polymorphisms and respiratory diseases.