Polymorphic variants of the genes for enzymes of the antioxidant system, apoptosis and inflammation as potential predictors of myocardial infarction
Myocardial infarction (MI) is a multifactorial polygenic disease that develops as a result of a complex interaction of numerous genetic factors and the external environment. Accordingly, the contribution of each of them separately is usually not large and may significantly depend on the state of oth...
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Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2024-11-01
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| Series: | Вавиловский журнал генетики и селекции |
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| Online Access: | https://vavilov.elpub.ru/jour/article/view/4352 |
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| author | T. R. Nasibullin V. V. Erdman Y. R. Timasheva I. A. Tuktarova A. A. Petinseva G. F. Korytina |
| author_facet | T. R. Nasibullin V. V. Erdman Y. R. Timasheva I. A. Tuktarova A. A. Petinseva G. F. Korytina |
| author_sort | T. R. Nasibullin |
| collection | DOAJ |
| description | Myocardial infarction (MI) is a multifactorial polygenic disease that develops as a result of a complex interaction of numerous genetic factors and the external environment. Accordingly, the contribution of each of them separately is usually not large and may significantly depend on the state of other accompanying factors. The purpose of the study was to search for informative predictors of MI risk based on polygenic analysis of polymorphic variants of (1) the antioxidant defense enzyme genes PON1 (rs662), PON2 (rs7493), CAT (rs1001179), MSRA (rs10098474) and GSTP1 (rs1695); (2) the apoptosis genes CASP8 (rs3834129), TP53 (rs1042522) and BCL2 (rs12454712); and (3) the inflammation genes CRP (rs1205), CX3CR1 (rs3732378), IL6 (rs1800795) and CCL2 (rs1024611). 591 DNA samples were used in the study (280 patients with the onset at 30 to 60 years, with an average age of 46.02 ± 6.17, and 311 control subjects aged 30 to 62, with an average age of 44.65 ± 7.07). All the participants were male and Tatars by ethnicity. The logistic regression analysis with various models demonstrated associations with MI of polymorphic variants of the genes CX3CR1 (rs3732378) (overdominant model – G/G + A/A vs A/G P = 0.0002, OR = 1.9), MSRA (rs10098474) (dominant model – T/T vs T/C + C/C P = 0.015, OR = 1.51), CCL2 (rs1024611) (recessive model – P = 0.0007 – A/A + A/G vs G/G OR = 2.63), BCL2 (rs12454712) (log-additive model – *C allele, P = 0.005, OR = 1.38). Using the Monte Carlo method and Markov chains (APSampler), combinations of alleles/ genotypes of the studied polymorphic loci associated with a high risk of MI were obtained, which, in addition to those identified during single-locus analysis, contained polymorphic variants of the genes CASP8, TP53, CAT, PON2, CRP, IL6, GSTP1. Among the combinations obtained, a pairwise analysis of possible non-linear interactions between the identified combinations of alleles/genotypes was carried out, which showed synergistic interactions of the polymorphic variants CX3CR1*A/G and CASP8*I/I, MSRA*C and CRP*C, CAT*C/T and MSRA*C, CAT*C/T and CX3CR1*A contributing to the development of MI. Based on the results obtained using multivariate logistic regression analysis, a predictive model was built to assess the risk of developing MI, the predictive ability of which reached the value AUC = 0.71 (AUC – area under the curve in ROC analysis). |
| format | Article |
| id | doaj-art-a65b18f7b3924ec79ce0c37c26763a02 |
| institution | Kabale University |
| issn | 2500-3259 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj-art-a65b18f7b3924ec79ce0c37c26763a022025-02-01T09:58:13ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592024-11-0128779280010.18699/vjgb-24-871514Polymorphic variants of the genes for enzymes of the antioxidant system, apoptosis and inflammation as potential predictors of myocardial infarctionT. R. Nasibullin0V. V. Erdman1Y. R. Timasheva2I. A. Tuktarova3A. A. Petinseva4G. F. Korytina5Institute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Centre of the Russian Academy of SciencesInstitute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Centre of the Russian Academy of SciencesInstitute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Centre of the Russian Academy of SciencesInstitute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Centre of the Russian Academy of SciencesInstitute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences; Ufa University of Science and TechnologyInstitute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Centre of the Russian Academy of SciencesMyocardial infarction (MI) is a multifactorial polygenic disease that develops as a result of a complex interaction of numerous genetic factors and the external environment. Accordingly, the contribution of each of them separately is usually not large and may significantly depend on the state of other accompanying factors. The purpose of the study was to search for informative predictors of MI risk based on polygenic analysis of polymorphic variants of (1) the antioxidant defense enzyme genes PON1 (rs662), PON2 (rs7493), CAT (rs1001179), MSRA (rs10098474) and GSTP1 (rs1695); (2) the apoptosis genes CASP8 (rs3834129), TP53 (rs1042522) and BCL2 (rs12454712); and (3) the inflammation genes CRP (rs1205), CX3CR1 (rs3732378), IL6 (rs1800795) and CCL2 (rs1024611). 591 DNA samples were used in the study (280 patients with the onset at 30 to 60 years, with an average age of 46.02 ± 6.17, and 311 control subjects aged 30 to 62, with an average age of 44.65 ± 7.07). All the participants were male and Tatars by ethnicity. The logistic regression analysis with various models demonstrated associations with MI of polymorphic variants of the genes CX3CR1 (rs3732378) (overdominant model – G/G + A/A vs A/G P = 0.0002, OR = 1.9), MSRA (rs10098474) (dominant model – T/T vs T/C + C/C P = 0.015, OR = 1.51), CCL2 (rs1024611) (recessive model – P = 0.0007 – A/A + A/G vs G/G OR = 2.63), BCL2 (rs12454712) (log-additive model – *C allele, P = 0.005, OR = 1.38). Using the Monte Carlo method and Markov chains (APSampler), combinations of alleles/ genotypes of the studied polymorphic loci associated with a high risk of MI were obtained, which, in addition to those identified during single-locus analysis, contained polymorphic variants of the genes CASP8, TP53, CAT, PON2, CRP, IL6, GSTP1. Among the combinations obtained, a pairwise analysis of possible non-linear interactions between the identified combinations of alleles/genotypes was carried out, which showed synergistic interactions of the polymorphic variants CX3CR1*A/G and CASP8*I/I, MSRA*C and CRP*C, CAT*C/T and MSRA*C, CAT*C/T and CX3CR1*A contributing to the development of MI. Based on the results obtained using multivariate logistic regression analysis, a predictive model was built to assess the risk of developing MI, the predictive ability of which reached the value AUC = 0.71 (AUC – area under the curve in ROC analysis).https://vavilov.elpub.ru/jour/article/view/4352myocardial infarctionoxidative stressapoptosisinflammation |
| spellingShingle | T. R. Nasibullin V. V. Erdman Y. R. Timasheva I. A. Tuktarova A. A. Petinseva G. F. Korytina Polymorphic variants of the genes for enzymes of the antioxidant system, apoptosis and inflammation as potential predictors of myocardial infarction Вавиловский журнал генетики и селекции myocardial infarction oxidative stress apoptosis inflammation |
| title | Polymorphic variants of the genes for enzymes of the antioxidant system, apoptosis and inflammation as potential predictors of myocardial infarction |
| title_full | Polymorphic variants of the genes for enzymes of the antioxidant system, apoptosis and inflammation as potential predictors of myocardial infarction |
| title_fullStr | Polymorphic variants of the genes for enzymes of the antioxidant system, apoptosis and inflammation as potential predictors of myocardial infarction |
| title_full_unstemmed | Polymorphic variants of the genes for enzymes of the antioxidant system, apoptosis and inflammation as potential predictors of myocardial infarction |
| title_short | Polymorphic variants of the genes for enzymes of the antioxidant system, apoptosis and inflammation as potential predictors of myocardial infarction |
| title_sort | polymorphic variants of the genes for enzymes of the antioxidant system apoptosis and inflammation as potential predictors of myocardial infarction |
| topic | myocardial infarction oxidative stress apoptosis inflammation |
| url | https://vavilov.elpub.ru/jour/article/view/4352 |
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