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

Korytina, G. F.; Akhmadishina, L. Z.; Cilousova, O. S.; Загидуллин, Ш. З.; Victorova, T. V.

doi:10.1134/s1022795409070138

Cited by 11 publications

(10 citation statements)

References 24 publications

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“…SNPs in classical NFE2L2 targets such as glutathione S-transferase (GST) genes, NAD(P)H quinone oxidoreductase (NQO1), glutamate-cysteine ligase catalytic subunit (GCLC), and heme oxygenase-1 (HMOX1) have previously been shown to be associated with COPD (7,18,20,21,29,33,44,55,56,65,69). In contrast, other studies failed to find association of these genes with COPD-related phenotypes (23,24,57,67,68).…”

Section: Discussionmentioning

confidence: 83%

NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease

Sandford

Malhotra

Boezen

et al. 2012

Physiological Genomics

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An oxidant-antioxidant imbalance in the lung contributes to the development of chronic obstructive pulmonary disease (COPD) that is caused by a complex interaction of genetic and environmental risk factors. Nuclear erythroid 2-related factor 2 (NFE2L2 or NRF2) is a critical molecule in the lung's defense mechanism against oxidants. We investigated whether polymorphisms in the NFE2L2 pathway affected the rate of decline of lung function in smokers from the Lung Health Study (LHS)(n ϭ 547) and in a replication set, the Vlagtwedde-Vlaardingen cohort (n ϭ 533). We selected polymorphisms in NFE2L2 in genes that positively or negatively regulate NFE2L2 transcriptional activity and in genes that are regulated by NFE2L2. Polymorphisms in 11 genes were significantly associated with rate of lung function decline in the LHS. One of these polymorphisms, rs11085735 in the KEAP1 gene, was previously shown to be associated with the level of lung function in the Vlagtwedde-Vlaardingen cohort but not with decline of lung function. Of the 23 associated polymorphisms in the LHS, only rs634534 in the FOSL1 gene showed a significant association in the Vlagtwedde-Vlaardingen cohort with rate of lung function decline, but the direction of the association was not consistent with that in the LHS. In summary, despite finding several nominally significant polymorphisms in the LHS, none of these associations were replicated in the Vlagtwedde-Vlaardingen cohort, indicating lack of effect of polymorphisms in the NFE2L2 pathway on the rate of decline of lung function. genetic polymorphism; nuclear erythroid 2-related factor 2; forced expiratory volume in one second CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) is the result of a complex interaction of genetic and environmental risk factors (51) and is characterized by irreversible airflow obstruction that results from chronic inflammation and tissue remodeling. Although the main environmental risk factor for COPD is cigarette smoking, longitudinal studies show that only a minority of long-term cigarette smokers develops airflow limitation (15), suggesting that additional environmental and/or genetic factors are important. Family and twin studies have demonstrated that genetic factors play a key role in the etiology of COPD (41, 49). Furthermore, genome-wide association studies of lung function (19,46,50,58,63), COPD (8, 47), and emphysema (32) have identified several putative loci underlying these traits.Several lines of evidence suggest that oxidant-antioxidant imbalance in the lung plays a major role in the pathogenesis of COPD. A measure of oxidative stress in the blood (thiobarbituric acid-reactive substances) was shown to correlate inversely with lung function in a population study (53). In addition, reactive oxygen species released by circulating neutrophils play a role in the development of airflow limitation (38). Furthermore, antioxidant nutrients have been associated with preservation of lung function (28, 42).Nuclear erythroid 2-related factor 2 (NFE2L2 or NRF2) is a basic leucine z...

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Section: Discussionmentioning

confidence: 83%

NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease

Sandford

Malhotra

Boezen

et al. 2012

Physiological Genomics

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“…It has been suggested that GSTP1 105Val has a higher catalytic efficiency to the metabolism of carcinogenic aromatic epoxides ( 18 ). In a study on Turkish and Japanese populations, 105Ile was connected with COPD, while in the research on Indian, Tunisian and Russian populations, 105Val allele represented a significant risk factor for COPD ( 18 , 32 , 35 – 37 ). However, numerous studies did not confirm the role of this polymorphism in COPD pathogenesis, which is in concordance with the results of our study ( 24 , 28 , 30 ).…”

Section: Discussionmentioning

confidence: 97%

Association of Functional Variants of Phase I and II Genes with Chronic Obstructive Pulmonary Disease in a Serbian Population / Udruženost Funkcionalnih Varijanti Gena Faze I I Ii Sa Hroničnom Opstruktivnom Bolešću Pluća U Srpskoj Populaciji

Stanković¹,

Nikolić²,

Tomović³

et al. 2015

Journal of Medical Biochemistry

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SummaryBackgroundChronic obstructive pulmonary disease (COPD) is a complex disorder characterized by increased oxidative stress. Functional genetic variants of phase I and II genes are implicated in oxidants–antioxidants imbalance and may be involved in COPD development. In this study, we aimed to investigate the role of cytochrome P450 (CYP), glutathione S-transferase (GST) and microsomal epoxide hydrolase (mEH) functional variants in the pathogenesis of COPD in a Serbian population.MethodsThe genotypes of 122 COPD patients and 100 controls with normal lung function were determined for CYP1A1 *1A/*2A, CYP2E1 *1A/*5B, GSTM1 null, GSTT1 null GSTP1 Ile105Val, mEH Tyr113His and mEH His139Arg gene variants.ResultsResults obtained showed that GSTM1 null variant was significantly more represented in COPD patients than in controls (61.5% vs. 47.0%; OR=1.80; p=0.042). Also, a significant difference was observed for combinations of GSTM1 null and GSTP1 105Val/(Val) (38.5% vs. 24.0%; OR=1.98; p=0.029), as well as for CYP1A1 *1A/*2A, GSTM1 null and mEH 113His/(His) genotypes (7.4% vs. 1.0%; OR=7.88; p=0.025).ConclusionsThese are the first data concerning the analysis of the variants of phase I and II genes in the pathogenesis of COPD in a Serbian population. Results obtained in this study open up the possibility for thorough analyses of the role of genetic factors in COPD on larger cohorts. Also, they implicate the importance of previously described genetic associations with COPD in our population, as well as reveal a new one, not reported so far.

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“…Отсутствие или ослабление ферментативной активности повышает восприимчивость организма к вредным воздействиям и, как следствие, к увеличению риска развития ряда заболеваний. Существуют многочисленные исследования, показывающие связь полиморфных вариантов генов GSTM1, GSTT1 и GSTP1 с онкологическими заболеваниями, болезнями легких и верхних дыхательных путей, диабетом 2 типа [5][6][7][8][9][10]. Частота аллелей и генотипов генов семейства GSTs изучена во многих мировых и российских популяциях [3][4][5][6][7][11][12][13][14][15][16][17].…”

Section: материалы и методыunclassified

“…Существуют многочисленные исследования, показывающие связь полиморфных вариантов генов GSTM1, GSTT1 и GSTP1 с онкологическими заболеваниями, болезнями легких и верхних дыхательных путей, диабетом 2 типа [5][6][7][8][9][10]. Частота аллелей и генотипов генов семейства GSTs изучена во многих мировых и российских популяциях [3][4][5][6][7][11][12][13][14][15][16][17]. Однако до сих пор не полностью охвачены исследованиями популяции Сибири, открытым также остается вопрос о распределении полиморфных вариантов среди потомков межэтнических браков, учитывая всё возрастающую частоту последних.…”

Section: материалы и методыunclassified

Distribution of polymorphic variants of genes for xenobiotic biotransformation GSTM1, GSTT1 and GSTP1 in populations of native inhabitants and Russians of Eastern Siberia

Tabikhanova¹,

Osipova²,

Воронина³

et al. 2020

Nauchno-Prakticheskii Zhurnal «Medicinskaia Genetika»

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Актуальность. Изучение полиморфизма генов системы биотрансформации ксенобиотиков, ассоциированных с рядом многофакторных заболеваний - важное направление современных медико-генетических исследований. Цель и задачи - выявить этнические особенности распределения полиморфных вариантов генов GSTM1, GSTT1 и GSTP1 среди бурят, телеутов и русских Восточной Сибири. Материалы и методы. Изучены выборки восточных (N=139) и западных (N=284) бурят, метисов западных бурят с русскими (N=47), телеутов (N=115) и русских Восточной Сибири (N=122). Выявление генотипов GSTM1 0/0 и GSTT1 0/0 проводилось методом мультиплексной полимеразной цепной реакции в режиме реального времени, генотипирование GSTP1 проводили в режиме реального времени с использованием TaqMan-зондов. Результаты. Встречаемость генотипа GSTM1 0/0 среди восточных и западных бурят составляет 37,7% и 57,7% соответственно (51,4% в суммарной выборке бурят), среди русских - 42,6%. Статистически значимо меньшая частота показана у телеутов - 17,4%. Частота GSTТ1 0/0 у восточных и западных бурят равна 40,8% и 27,6% соответственно, у русских статистически значимо меньше - 18%, у телеутов - 24,8%. Для метисов показаны промежуточные значения частот GSTM1 0/0 и GSTТ1 0/0. Аллель GSTP1 1405G встречается среди восточных и западных бурят с частотой 27,7% и 19,2% соответственно, у русских - 31,8%, телеутов - 24,8%. Различие русских с западными бурятами статистически значимо. Частота аллеля GSTP1 2285T среди восточных (4,9%), западных (1,8%) бурят и телеутов (2,2%) меньше, чем среди русских (8,3%). Отличие русских от западных бурят и телеутов, является статистически значимым. Выводы. В суммарной выборке бурят показаны повышенные частоты генотипов GSTM1 0/0 и GSTТ1 0/0, ассоциированых, по данным литературы, с некоторыми многофакторными заболеваниями по сравнению с телеутами и русскими. В обеих выборках бурят статистически значимо повышена частота комбинированного генотипа, приводящего к отсутствию активности ферментов. В то же время у телеутов частота индивидов с генотипической комбинацией GSTM1 +GSTТ1 +, ответственной за нормальную ферментативную активность, статистически значимо выше. Частоты аллелей 1405G и 2285T гена GSTP1 среди бурят и телеутов понижены по сравнению с русскими. Метисация способствует изменению частоты аллелей. Статистически значимые различия в частотах вариантов GSTM1, GSTТ1 и GSTP1 внутри бурятского этноса могут свидетельствовать о его генетической неоднородности. Relevance. The study of the gene polymorphism of the system biotransformation of xenobiotics, which are associated with a number of multifactorial diseases, is an important area of modern medical genetic research. The aim and tasks are to reveal ethnic features in the distribution of polymorphic variants of genes GSTM1, GSTT1 and GSTP1 among Buryats, Teleuts and Russians of Eastern Siberia. Materials and methods. The samples of Eastern (N=139) and Western (N=284) Buryats, métis Western Buryats with Russians (N=47), Teleuts (N=115) and Russians of East Siberia (N=122) are studied. Detection of GSTM1 0/0 and GSTT1 0/0 was carried out through multiplex real-time PCR. Genotyping of GSTP1 was performed using TaqMan real-time PCR. Results. The occurrence of GSTM1 0/0 among Eastern and Western Buryats is 37.7% and 57.7% respectively (51.4% for the total sample of Buryats), among Russians - 42.6%. Significantly lower frequency is shown in Teleuts-17.4%. The frequency of GSTT1 0/0 in Eastern and Western Buryats is 40.8% and 27.6% respectively. It is significantly lower in Russians - 18%, in Teleuts - 24.8%. Mestis shows intermediate frequencies of GSTM1 0/0 and GSTТ1 0/0. GSTP1 1405G is found among Eastern and Western Buryats with 27.7% and 19.2% frequency, respectively, in Russians - 31.8%, Teleuts - 24.8%. The difference of Russians with Western Buryats is statistically significant. The frequencies of GSTP1 2285T among Eastern (4.9%), Western (1.8%) Buryats and Teleuts (2.2%) are lower than frequency among Russians (8.3%). The difference between Russians and Western Buryats with Teleuts is statistically significant. Summary. There are increased frequencies of GSTM1 0/0 and GSTT1 0/0 in the total cohort of Buryats in comparison with Teleuts and Russians. According to the literature data, these genotypes are associated with multi-factorial diseases. In both samples of Buryats, there is a statistically significantly increased frequency of the combined genotype resulting in the absence of enzyme activity. At the same time, there is a statistically significantly increased frequency of individuals with a genotypic combination GSTM1 +GSTT1 + responsible for normal enzymatic activity in the sample of Teleuts. There are reduced frequencies of risk-alleles GSTP1 1405G and 2285T among Buryats and Teleuts in comparison with Russians. Metisation changes the frequency of risk alleles. Significant differences in the frequencies of GSTM1, GSTT1 and GSTP1 within the Buryat ethnic group may indicate its genetic heterogeneity.

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

Cited by 11 publications

References 24 publications

NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease

NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease

Association of Functional Variants of Phase I and II Genes with Chronic Obstructive Pulmonary Disease in a Serbian Population / Udruženost Funkcionalnih Varijanti Gena Faze I I Ii Sa Hroničnom Opstruktivnom Bolešću Pluća U Srpskoj Populaciji

Distribution of polymorphic variants of genes for xenobiotic biotransformation GSTM1, GSTT1 and GSTP1 in populations of native inhabitants and Russians of Eastern Siberia

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