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Impact of Genetic and Epigenetic Factors on the Oxidative Stress in Cardiovascular Disease

  • Shiva Krishna Katkam
  • Bobbala Indumathi
  • Shaik Mohammad Naushad
  • Vijay Kumar Kutala
Chapter

Abstract

Cardiovascular disease (CVD) is one of the most common causes of deaths globally. Oxidative stress is documented to be one of the potential risk factors for CVD. This review focuses on genetic and epigenetic factors contributing toward CVD risk. Certain genetic variants in oxidants, i.e., NADPH oxidase p22Phox rs4673, eNOS (-786 T>C, 894 G>T, and 27bp VNTR), MPO (-463 and -129 GA-genotypes), XO 69901 A>C, COX2 (rs5277 and rs20417), and ALOX15 (rs2619112 and rs7217186), were reported to increase CVD risk. Similarly, genetic variants in antioxidants, i.e., SOD1 (rs9974610, rs10432782, rs1041740), SOD2 (V16A, C24T), GPX1 Pro198Leu, NQO1 C609T, PON1 Q192R, and TXNIP (rs7212 and rs7211), were also shown to exhibit positive association with CVD risk. Apart from oxidants and antioxidants, folate and xenobiotic metabolic pathways were also investigated due to their direct influence on synthesis, methylation, and repair of DNA. Among the functional variants of folate pathway, GCPII H475Y, MTHFR C677T, and MTRR A66G were reported to increase CVD risk, thus influencing S-adenosylmethionine/S-adenosyl homocysteine ratio. Two genetic variants, i.e., cSHMT C1420T and TYMS 5’-UTR 28bp tandem repeat, were shown to confer protection by inducing the futile folate cycle and by increasing the flux of folate toward remethylation of homocysteine, respectively. Among the xenobiotic variants, CYP1A1 CAC and TAC haplotypes and GSTT1 and GSTM1 null variants contribute toward CVD risk by inducing quinone and semiquinone synthesis and by preventing conjugation of glutathione, respectively. These two process trigger mutagenicity. CYP1A1 TAC haplotype and CYP4F2 rs2108622 confer protection against CVD. Hypermethylation of ER-alpha, ER-beta, p15(INK4b), FOXP3, and DDAH2 was associated with CVD risk, which is attributed to altered ER-signaling, increased oxidative stress, and impaired synthesis of Treg cells. Factor VII hypermethylation confers protection against CVD. In a nut shell, interplay of genetic and epigenetic factors in oxidant–antioxidant system modulates susceptibility to CVD.

Keywords

Cardiovascular diseases Oxidants Folate pathway Xenobiotic pathway Epigenetics Methylation 

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Shiva Krishna Katkam
    • 1
  • Bobbala Indumathi
    • 1
  • Shaik Mohammad Naushad
    • 2
  • Vijay Kumar Kutala
    • 1
  1. 1.Department of Clinical Pharmacology & TherapeuticsNizam’s Institute of Medical Sciences HyderabadHyderabadIndia
  2. 2.Biochemical Genetics & Pharmacogenomics LabSandor Life Sciences Pvt Ltd, HyderabadHyderabadIndia

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