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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.

Figure 1A-C

Superoxide dismutase (SOD) activity (mU/g hemoglobin (Hb)) in participants with various CYP2E1 genotypes (A) PstI, (B) RsaI, and (C) DraI (solid bars = wild type, open bars = heterozygous, hatched bars = variant) paired with NQO1 genotypes (WT = wild type, Het = heterozygous, and Var = variant), and various blood lipid profiles. Design for each panel: upper left quadrant is normolipidemia, upper right quadrant is hypertriglyceridemia, lower left quadrant is hypercholesterolemia, and lower right quadrant is combined hyperlipidemia. DraIdenotes the allele with a polymorphic site recognized by this restriction enzyme localized in intron 6 at position T7632 A (rs6413432). PstI indicates the allele with a point mutation recognized by PstI in the 5′-flanking region at G1293C (rs3813867) and RsaIindicates the allele with a point mutation recognized by RsaI in the 5′-flanking region at C1053T (rs2031920). Error bars ± SE. *P < 0.05.
Superoxide dismutase (SOD) activity (mU/g hemoglobin (Hb)) in participants with various CYP2E1 genotypes (A) PstI, (B) RsaI, and (C) DraI (solid bars = wild type, open bars = heterozygous, hatched bars = variant) paired with NQO1 genotypes (WT = wild type, Het = heterozygous, and Var = variant), and various blood lipid profiles. Design for each panel: upper left quadrant is normolipidemia, upper right quadrant is hypertriglyceridemia, lower left quadrant is hypercholesterolemia, and lower right quadrant is combined hyperlipidemia. DraIdenotes the allele with a polymorphic site recognized by this restriction enzyme localized in intron 6 at position T7632 A (rs6413432). PstI indicates the allele with a point mutation recognized by PstI in the 5′-flanking region at G1293C (rs3813867) and RsaIindicates the allele with a point mutation recognized by RsaI in the 5′-flanking region at C1053T (rs2031920). Error bars ± SE. *P < 0.05.

Figure 2A-C

Malondialdehyde (MDA) level (μΜ) in participants with various CYP2E1 genotypes (A) PstI, (B) RsaI, and (C) DraI (solid bars = wild type, open bars = heterozygous, hatched bars = variant) paired with NQO1 genotypes (WT wild type, Het heterozygous, and Var variant), and various blood lipid profiles. Design for each panel : upper left quadrant is normolipidemia, upper right quadrant is hypertriglyceridemia, lower left quadrant is hypercholesterolemia, and lower right quadrant is combined hyperlipidemia. DraI denotes the allele with a polymorphic site recognized by this restriction enzyme localized in intron 6 at position T7632A (rs6413432). PstI indicates the allele with a point mutation recognized by PstI in the 5′-flanking region at G1293C (rs3813867) and RsaI indicates the allele with a point mutation recognized by RscaI inthe 5′-flanking region at C1053T (rs2031920). Error bars ± SE.*P<0.05.
Malondialdehyde (MDA) level (μΜ) in participants with various CYP2E1 genotypes (A) PstI, (B) RsaI, and (C) DraI (solid bars = wild type, open bars = heterozygous, hatched bars = variant) paired with NQO1 genotypes (WT wild type, Het heterozygous, and Var variant), and various blood lipid profiles. Design for each panel : upper left quadrant is normolipidemia, upper right quadrant is hypertriglyceridemia, lower left quadrant is hypercholesterolemia, and lower right quadrant is combined hyperlipidemia. DraI denotes the allele with a polymorphic site recognized by this restriction enzyme localized in intron 6 at position T7632A (rs6413432). PstI indicates the allele with a point mutation recognized by PstI in the 5′-flanking region at G1293C (rs3813867) and RsaI indicates the allele with a point mutation recognized by RscaI inthe 5′-flanking region at C1053T (rs2031920). Error bars ± SE.*P<0.05.

Odds ratios for oxidative stress markers according to CYP2E1 and NQO1 polymorphism and lipid profile

Number (%)Oxidative stress markerOdds ratio (95% CI)

Sex, smoking, and alcohol consumption were adjusted for odds ratio, GSH = reduced glutathione, GPx = glutathione peroxidase, SOD, superoxide dismutase, CAT = catalase, and MDA = malondialdehyde.

P
CYP2E1:PstIReference1.0
Wild-typeGSH0.996 (0.997-1.02)0.66
n= 984 (71.3)CAT0.73 (0.28-1.91)0.52
• HeterozygousSOD0.58 (0.33-1.03)0.06
n= 351 (25.4)GPx2.53 (1.29-4.96)0.007
MDA1.24 (0.79-1.97)0.35
• VariantGSH1.00 (0.96-1.05)0.94
n = 45 (3.3)CAT6.49 (0.86-48.8)0.07
SOD0.38 (0.09-1.54)0.17
GPx3.33 (0.65-17.15)0.15
MDA0.81 (0.27-2.46)0.72
CYP2E1:RsaIReference1.0
• Wild-typeGSH0.997 (0.98-1.02)0.73
n= 979 (70.9)CAT0.60 (0.23-1.56)0.29
• HeterozygousSOD0.59 (0.33-1.05)0.07
n= 353 (25.6)GPx2.58 (1.31-5.05)0.006
MDA1.27 (0.80-2.01)0.31
• VariantGSH1.01 (0.97-1.05)0.61
n = 48 (3.5)CAT7.22 (1.05-48.8)0.004
SOD0.19 (0.05ndash;0.77)0.20
GPx2.34 (048-114)0.24
MDA1.21 (043-3.52)0.71
CYP2E1:DraIReference1.0
• Wild-typeGSH0.99 (0.97-1.01)0.26
n= 839 (60.8)CAT0.68 (0.28-1.65)0.40
• HeterozygousSOD0.64 (0.38-1.09)0.10
n= 464 (33.6)GPx1.79 (0.96-3.33)0.07
MDA0.99 (0.79-1.97)0.97
• VariantGSH0.99 (0.95-1.03)0.58
n = 77 (5.6)CAT2.32 (042-13.0)0.34
SOD0.78 (0.26-2.28)0.64
GPx1.92 (0.53 −6.90)0.32
MDA1.08 (045-2.59)0.86
NQO1 *2Reference1.0
• Wild-typeGSH1.02 (0.998-1.04)0.08
n=438 (31.7)CAT1.45 (0.57-3.66)0.44
• HeterozygousSOD1.31 (0.75-2.28)0.35
n=690 (50.0)GPx0.90 (0.47-1.72)0.74
MDA0.89 (0.56-1.40)0.61
• VariantGSH1.02 (0.99-1.04)0.19
n=252 (18.3)CAT0.75 (0.22-2.53)0.65
SOD1.09 (0.53-2.25)0.81
GPx1.98 (0.84-4.64)0.12
MDA1.15 (0.64-2.05)0.65
Cholesterol<200 mg/dLReference1.0
n= 320 (23.2)
Cholesterol≥200 mg/dLGSH1.01 (0.99-1.03)0.42
n= 1060 (76.8)CAT0.68 (0.26-1.79)0.43
SOD0.85 (0.48-1.50)0.57
GPx0.59 (0.30-1.17)0.13
MDA1.85 (1.14-2.98)0.01
Triglyceride < 150 mg/dLReference1.0
n= 874 (63.3)
TriglycerideGSH0.99 (0.98-1.01)0.56
≥200 mg/dLCAT0.42 (0.18-1.01)0.05
n= 506 (36.7)SOD1.13 (0.68-1.89)0.64
GPx1.05 (0.57-1.93)0.87
MDA2.54 (1.66-3.89)<0.01

Demographic characteristics and distribution of the metabolic enzyme gene polymorphisms of the study population

CharacteristicsLipid profile
Normolipidemia (n = 236)Hypercholesterolemia (n = 638)Hypertriglyceridemia (n = 84)Combined hyperlipidemia (n = 422)P

P generated using a general-linear model: multivariate test, χ2 test for genotype and lifestyle features

Age (years)

Data = mean ± SD or n (%)

51.6±4.751.0±4451.9±4.851.9±4.30.08
Weight (kg)

Data = mean ± SD or n (%)

67.1 ±11.564.5 ± 10.869.3 ± 10.969.6 ±10.60.46
Height (cm)

Data = mean ± SD or n (%)

164.4 ±8.2163.3 ±7.6164.3 ±7.7164.8 ±7.50.16
BMI (kg/m2)

Data = mean ± SD or n (%)

24.8 ±3.4824.1 ±3.2325.6±3.38

hypercholesterolemia or hypertriglyceridemia compare with normolipidemia

25.6 ±3.41<.001

hypercholesterolemia or hypertriglyceridemia compare with normolipidemia

Cholesterol (mg/dL)

Data = mean ± SD or n (%)

179.0 ±19.12242.6 ±28.93

hypercholesterolemia or hypertriglyceridemia compare with normolipidemia

180.1 ±18.29253.1 ±35.80

combined hyperlipidemia compared with normolipidemia

<.001

hypercholesterolemia or hypertriglyceridemia compare with normolipidemia

,0.02

combined hyperlipidemia compared with normolipidemia

Triglyceride (mg/dL)

Data = mean ± SD or n (%)

93.3 ±32.4098.9 ±30.08224.5 ± 95.70

hypercholesterolemia or hypertriglyceridemia compare with normolipidemia

233.7 ±105.32

combined hyperlipidemia compared with normolipidemia

<0.001

hypercholesterolemia or hypertriglyceridemia compare with normolipidemia

combined hyperlipidemia compared with normolipidemia

LDL-C (mg/dL)

Data = mean ± SD or n (%)

113.9±1547164.6 ± 30.13

hypercholesterolemia or hypertriglyceridemia compare with normolipidemia

95.8± 19.12159.4 ±3642

combined hyperlipidemia compared with normolipidemia

<.001

hypercholesterolemia or hypertriglyceridemia compare with normolipidemia

, 0.003

combined hyperlipidemia compared with normolipidemia

HDL-C (mg/dL)

Data = mean ± SD or n (%)

50.9 ±10.3156.6±11.56

hypercholesterolemia or hypertriglyceridemia compare with normolipidemia

43.2 ±9.9347.3 ±9.71<0.001

hypercholesterolemia or hypertriglyceridemia compare with normolipidemia

CYP2E1:CYP2E1 *5B (RsaI/PstI)
 No. of c1c1 (WT)175/176 (≈74)450/453 (≈71)54/55 (=65)300/300 (71)<0.001

significant difference between group of lipid profiles

 No.of c1c2 (Het)50/50 (21)167/165 (=26)26/26 (31)110/110 (26)0.20,0.25
 No.of c2c2 (Var)11/10 (≈4)21/20 (=3)4/3 (=4)12/12 (3)0.39,0.29
CYP2EI*6 (DraI)
 No. of DD (WT)148 (63)380 (60)48 (57)263 (62)<0.001

significant difference between group of lipid profiles

 No. of DC (Het)74 (31)224 (35)30 (36)136 (32)0.07
 No. of CC (Var)14 (6)34 (5)6 (7)23 (6)0.50
 NQO1 NQO1 *2
 No. of CC (WT)71 (30)210 (33)30 (36)127 (30)0.10
 No of CT (Het)116 (49)318 (50)41 (48)215 (51)<0.001

significant difference between group of lipid profiles

 No. of TT (Var)49 (21)110 (17)13 (16)80 (19)0.41
Sex
 Male170 (72)419 (66)63 (75)331 (78)<0.001

significant difference between group of lipid profiles

 Female66 (28)219 (34)21 (25)91 (22)0.21
Smoking33 (14)64 (10)11 (13)82 (19)<0.001

significant difference between group of lipid profiles

Nonsmoking203 (86)574 (90)73 (87)340 (81)0.001
Alcohol drinking115 (49)304 (48)43 (51)248 (59)<0.001

significant difference between group of lipid profiles

Alcohol abstinence121 (51)334 (52)41 (49)174 (41)0.02*
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