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Cardiovasc Toxicol. 2019 Jul 22. doi: 10.1007/s12012-019-09544-7. [Epub ahead of print]

Association of Genetic Variations in NRF2, NQO1, HMOX1, and MT with Severity of Coronary Artery Disease and Related Risk Factors.

Author information

1
Biomedical Sciences Program, Graduate School, Khon Kaen University, Khon Kaen, 40002, Thailand.
2
Cardiovascular Research Group, Khon Kaen University, Khon Kaen, 40002, Thailand.
3
School of Medical Technology, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand.
4
Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
5
Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
6
Queen Sirikit Heart Center of the Northeast Hospital, Khon Kaen University, Khon Kaen, 40002, Thailand.
7
Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand. schatr@kku.ac.th.
8
Cardiovascular Research Group, Khon Kaen University, Khon Kaen, 40002, Thailand. schatr@kku.ac.th.

Abstract

NRF2 is a transcription factor which, during oxidative stress, activates transcription of its target antioxidant genes. Polymorphisms in NRF2 and its target antioxidant genes: HMOX-1, NQO1, and MT, have been associated with cardiovascular diseases (CVDs) and diabetes in various ethnic groups, however, with variable results. The aim of this study was to investigate the association of NRF2, HMOX-1, NQO1, and MT gene polymorphisms with CVD risk factors in Thais. The study was conducted in two groups: group with high-risk for coronary artery disease (CAD) and health check-up group. Polymorphisms in NRF2 (rs6721961), NQO1 (rs1800566), MT1A (rs11640851), and HMOX-1 (rs2071746) were genotyped. Expressions of NRF2, HMOX-1, and NQO1 were also determined. In high-risk group, NRF2 rs6721961-TT was associated with CAD [OR (95% CI) 5.07 (1.42-18.10)] and severity of coronary atherosclerosis [Gensini score > 32, OR (95% CI) 4.31 (1.67-11.09)]; rs6721961 GT and TT revealed significant association with lower mRNA expression than GG (p = 0.021). NQO1 rs1800566 also revealed association with CAD, only in female. Combined effect of NQO1-rs1800566, HMOX1-rs2071746, and MT1A-rs11640851 was evaluated on the risks of DM and hypertension. With a combination of risk alleles as genetic risk score (GRS), the highest GRS (score 6) increased risk for hypertension, comparing with GRS 0-2 [OR (95% CI) 1.89 (1.02-3.49)]; group with score 5-6 revealed association with risk of DM [OR (95% CI) 1.481 (1.08-2.04)]. In conclusion, NRF2 rs6721961 associated with CAD and severity of coronary atherosclerosis. NQO1 rs1800566 also associated with CAD, only in female. Combined polymorphisms of three NRF2-regulated genes increased risk of DM and hypertension.

KEYWORDS:

Cardiovascular disease (CVD); Diabetes mellitus; Heme oxygenase-1 (HMOX1); Metallothionein (MT); NAD(P)H: quinone oxidoreductase 1 (NQO1); Nuclear factor (erythroid-derived 2)-like 2 (NRF2)

PMID:
31332605
DOI:
10.1007/s12012-019-09544-7

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