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Role of CYP2E1 and NQO1 polymorphisms in oxidative stress derived cancer in Thais with and without dyslipidemia

Pharrunrat Tanaviyutpakdee
Pharrunrat Tanaviyutpakdee
, 
Krongtong Yoovathaworn
Krongtong Yoovathaworn
, 
Jintana Sirivarasai
Jintana Sirivarasai
, 
Suwannee Chanprasertyothin
Suwannee Chanprasertyothin
, 
Pachara Panpunuan
Pachara Panpunuan
, 
Krittaya Petchpoung
Krittaya Petchpoung
, 
Aninthita Tatsaneeyapant
Aninthita Tatsaneeyapant
, 
Thunyachai Sura
Thunyachai Sura
, 
Sming Kaojarern
Sming Kaojarern
 and 
Piyamit Sritara
Piyamit Sritara
   | Jan 31, 2017
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Article Category: Original article
Published Online: Jan 31, 2017
Page range: 601 - 611
DOI: https://doi.org/10.5372/1905-7415.0904.430
Keywords
© 2015 Pharrunrat Tanaviyutpakdee, Krongtong Yoovathaworn, Jintana Sirivarasai, Suwannee Chanprasertyothin, Pachara Panpunuan, Krittaya Petchpoung, Aninthita Tatsaneeyapant, Thunyachai Sura, Sming Kaojarern, Piyamit Sritara
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Background

Hyperlipidemia can induce the endogenous production of reactive oxygen species (ROS), which may cause carcinogenesis. Cytochrome P450 (CYP) 2E1 activity, induced by various factors including polyunsaturated fatty acids, effects the incidence of cancers, whereas NQO1, a flavoprotein, may protect against ROS.

Objectives

To investigate the effect of CYP2E1 and NQO1 polymorphism on oxidative stress status in Thais with and without dyslipidemia.

Methods

We included 1380 apparently healthy employees of the Electricity Generating Authority of Thailand in this study. We determined their CYP2E1 and NQO1 genotypes and related these to blood lipid profiles, and circulating levels of antioxidant enzymes, malondialdehyde (MDA), and reduced glutathione (GSH). Lifestyle-related factors were determined from questionnaires.

Results

All tested genotype frequencies were in Hardy-Weinberg equilibrium. The heterozygous and variant genotype distribution and allele frequency of CYP2E1 *5B were less common than CYP2E1 *6. Heterozygous NQO1 was the most prevalent form. The frequency of the mutated allele CYP2E1 *5B was 0.16, CYP2E1 *6 was 0.22, and NQO1 *2 was 0.43. Significant differences were observed for blood cholesterol, triglyceride, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol between normolipidemic participants, and those with hypercholesterolemia, hypertriglyceridemia, and combined hyperlipidemia. Participants in the hyperlipidemic subgroup who bore any variant alleles of genes had higher plasma MDA and GSH levels, and superoxide dismutase and glutathione peroxidase activity, but lower catalase activity when compared with normolipidemic participants bearing wild-type alleles.

Conclusions

Variations in genetic disposition and dyslipidemia can modify oxidative stress status. Relatively more free radicals may be generated in individuals in subgroups with hyperlipidemia bearing any variant alleles.

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Language:
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