BACKGROUNDMany studies have suggested that cigarette smoking and polymorphisms of resistin and glutathione peroxidase-1 (GPx-1) genes are closely correlated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, few reports have investigated these associations with respect to NAFLD susceptibility. We, therefore, examined the distribution of polymorphisms in GPx-1 and resistin genes in NAFLD patients and healthy controls and analyzed the relationship between these polymorphisms and smoking status.

METHODSNine hundred NAFLD patients and 900 healthy controls were selected, and the genetic polymorphisms of resistin gene promoter-420C/G and GPx-1 gene Pro198Leu were analyzed by polymorphism-polymerase chain reaction (PCR) in DNA extracted from peripheral blood leukocytes. Interactions between the two mutants and the gene-environment interaction with cigarette smoking were also analyzed.

RESULTSGenotype frequencies of -420C/G (GG) and Pro198Leu (LL) were significantly higher in NAFLD cases (49.56% and 50.11%, respectively) compared with healthy controls (23.67% and 24.22%, respectively) (P = 0.0069; P = 0.0072). Moreover, the risk of NAFLD with -420C/G (GG) was significantly higher than in controls (odds ratio [OR] =3.1685, 95% confidence interval (CI) =1.9366-5.2073). Individuals carrying Pro198Leu (LL) had a high risk of NAFLD (OR = 3.1424, 95% CI = 1.7951-5.2367). Combined analysis of the polymorphisms showed that the -420C/G (GG)/Pro198Leu (LL) genotype was significantly more common in the NAFLD group than in the control group (39.44% vs. 12.78%, respectively, P = 0.0054), while individuals with -420C/G (GG)/Pro198Leu (LL) had a high risk of NAFLD (OR = 5.0357, 95% CI = 3.1852-7.8106). Moreover, the cigarette smoking rate in the NAFLD group was significantly higher than in the control group (OR = 1.8990, P = 0.0083 in the smoking index (SI) ≤400 subgroup; OR = 5.0937, P = 0.0051 in the SI >400 subgroup), and statistical analysis suggested a positive interaction between cigarette smoking and -420C/G (GG) (γ = 5.6018 in the SI ≤400 subgroup; γ = 4.4770 in the SI >400 subgroup) and Pro198Leu (LL) (γ = 5.7715 in the SI ≤400 subgroup; γ = 4.5985 in the SI >400 subgroup) in increasing the risk of NAFLD.

CONCLUSIONNAFLD risk factors include -420C/G (GG), Pro198Leu (LL) and cigarette smoking, and these three factors have a significant additive effect on NAFLD risk.

Female ; Genetic Predisposition to Disease ; genetics ; Glutathione Peroxidase ; genetics ; Humans ; Male ; Non-alcoholic Fatty Liver Disease ; metabolism ; Polymorphism, Single Nucleotide ; genetics ; Promoter Regions, Genetic ; genetics ; Resistin ; genetics ; Smoking ; genetics

BACKGROUNDGenetic mechanisms contribute to blood pressure regulation. This study investigated whether glutathione peroxidase (GPx-3) tag single nucleotide polymorphisms (SNPs) are associated with hypertension in the rural areas of Fuxin county, Liaoning province, China.

METHODSIndigenous Fuxin Han people participated, 523 unrelated hypertensives and 547 controls were recruited. All tag SNPs of GPx-3 gene were selected. We estimated SNP allele frequency in DNA pools with pyrosequencing.

RESULTSBefore Bonferroni correction, C allele frequency for rs8177417 was significantly higher in hypertensives than those in controls (23.4% vs. 19.3%, P = 0.014); T allele frequency for rs3828599 was significantly lower in hypertensives than those in controls (35.6% vs. 40.8%, P = 0.009). However, when a Bonferroni correction for multiple testing was applied, only the polymorphisms rs3828599 of GPx-3 gene was associated with hypertension (P = 0.045, OR: 0.833, 95%CI: 0.695 - 0.998).

CONCLUSIONThe polymorphism of rs3828599 of GPx-3 gene might be associated with hypertension in rural Han Chinese from Fuxin, Liaoning.

Aged ; Female ; Gene Frequency ; genetics ; Genetic Predisposition to Disease ; genetics ; Glutathione Peroxidase ; genetics ; Humans ; Hypertension ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics

OBJECTIVETo construct a Gpx1 and klk1 recombinant vector containing the kidney-specific promoter Ksp-cadherin.

METHODSHuman Gpx1, Klk1 and Ksp-cadherin cDNAs were amplified with PCR and inserted in a stepwise manner into the expressive vector pIRES-EGFP to construct the recombinant vector Ksp-cadherin-Gpx1-Klk1. The constructed vector was verified with restriction enzyme digestion and sequence analysis.

RESULTS AND CONCLUSIONThe recombinant expression vector Ksp-cadherin-Gpx1-Klk1 was constructed and identified successfully, which provides a potent tool for preparing transgenic animals to investigate gene therapy for ischemia-reperfusion injury in kidney transplantation.

Cadherins ; genetics ; Cloning, Molecular ; Genetic Therapy ; methods ; Genetic Vectors ; genetics ; Glutathione Peroxidase ; genetics ; Humans ; Kallikreins ; genetics ; Kidney ; metabolism ; Promoter Regions, Genetic ; genetics

OBJECTIVETo study the association between the single nucleotide polymorphisms (SNPs) of the 5'-untranslated region (5'-UTR) of phospholipid hydroperoxide glutathione peroxidase (GPx4 or PHGPx) gene and oligo- or asthenozoospermic male infertility.

METHODSThe 5'-UTR region of the GPx4 gene was amplified from infertile men and controls using the polymerase chain reaction and was analyzed for polymorphisms by direct sequencing.

RESULTSA total of 9 SNPs were present in the cohort, however there were no significant differences in these 9 SNPs between the case and control groups. According to the results of linkage disequilibrium analysis and haplotype construction, one haplotype (rs757229-rs757230-rs4588110-rs3746165-rs3746166: C-G-G-T-A) was present only in the control men, and significant difference was detected(P< 0.01).

CONCLUSIONThe SNPs of 5'-UTR region of the GPx4 gene might not be associated with oligo- or asthenozoospermic male infertility. However, the haplotype (rs757229-rs757230-rs4588110- rs3746165-rs3746166: C-G-G-T-A) might be a protective haplotype.

5' Untranslated Regions ; genetics ; Adult ; Alleles ; Gene Frequency ; Genotype ; Glutathione Peroxidase ; genetics ; Humans ; Infertility, Male ; genetics ; Linkage Disequilibrium ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; Young Adult

OBJECTIVETo construct a RNA interference lentiviral vector for human glutathione peroxidase 2 (GPX2) gene and observe the effect of GPX2 knockdown on cell apoptosis.

METHODSThe sequence of the small interfering RNA (siRNA) for GPX2 interference was inserted into the pSicoR vector. HepG2 cells were infected by the packaged si-GPX2 lentivirus and the expression of GPX2 in the infected cells was detected by both RT-PCR and Western blotting. Changes of cell apoptosis following the infection were analyzed by flow cytometry.

RESULTSThe lentiviral particles pSicoR-GPX2 were successfully packaged. The expression of GPX2 in the infected cells was obviously down-regulated at both RNA and protein levels. GPX2 knockdown caused increased apoptosis rate, increased Bax expression and lowered Bcl-2 expression in HepG2 cells.

CONCLUSIONWe have successfully constructed the lentiviral vector for RNA interference of human GPX2 gene.

Apoptosis ; Down-Regulation ; Genetic Vectors ; Glutathione Peroxidase ; genetics ; Hep G2 Cells ; Humans ; Lentivirus ; RNA Interference ; RNA, Small Interfering

OBJECTIVEThis study examined whether the two polymorphisms of GPX1 (198Pro--> Leu) and TXNRD2 (370Lys-->Arg) contributed alone or in combination, to the risk of gastric cancer development.

METHODSA total of 361 patients with gastric cancer and 363 cancer-free controls were recruited and their genotypes of the two polymorphisms were determined by polymerase chain reaction-based restrictive fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence interval (CI) were computed using unconditional logistic regression model.

RESULTSGPX1 and TXNRD2 polymorphisms individually were not associated with the risk of gastric cancer. Gene-gene interaction of GPX1 and TXNRD2 polymorphisms decreased the risk of gastric cancer. Carrying the protective genotype might decrease the risk at 62% (OR = 0.38, 95% CI = 0.26-0.55, P < 0.001) as compared with the risk genotype.

CONCLUSIONThe GPX1 198 Pro/Pro and TXNRD2 370Arg/Arg genotypes might be associated with the genetic susceptibility of gastric cancer.

Alleles ; Case-Control Studies ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Glutathione Peroxidase ; genetics ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Stomach Neoplasms ; genetics ; Thioredoxin Reductase 2 ; genetics

BACKGROUND/AIMS: Many patients with acute paraquat (PQ) intoxication die even at low PQ concentrations, whereas others with similar concentrations recover. Therefore, it is possible that individual differences in antioxidant capacity are responsible for the variable clinical outcome in patients with acute PQ intoxication. METHODS: We investigated whether there was a relationship between the genetic polymorphisms of SOD (V16A), catalase (C262T), and GPX1 (C593T) in 62 patients with acute PQ intoxication and the clinical outcomes of these patients. RESULTS: The frequency of the Mn-SOD V/V, V/A, and A/A genotypes were 56.3, 43.5, and 0% in survivors and 86.9, 13.1, and 0% in non-survivors (p > 0.05). The GPX1 C/C, C/T, and T/T genotypes were present in 100, 0, and 0% of all subjects. The catalase C/C, C/T, and T/T genotypes were present in 100, 0, and 0% of survivors, and in 82.6, 17.4, and 0% of non-survivors. Neither erythrocyte SOD activity nor catalase activity were significantly different between survivors and non-survivors. CONCLUSIONS: No association was found between clinical outcome of acute PQ intoxication and the genetic polymorphism of GPX1 (C593T) or the genetic polymorphisms or enzyme activity of superoxide dismutase (V16A) or catalase (C262T).
Acute Disease ; Adult ; Aged ; Catalase/*genetics ; Female ; Genotype ; Glutathione Peroxidase/genetics ; Humans ; Male ; Middle Aged ; Paraquat/*poisoning ; Poisoning/mortality ; *Polymorphism, Genetic ; Superoxide Dismutase/*genetics

BACKGROUND/OBJECTIVES: Glutathione s-transferase (GST) is involved in the formation of a multigene family comprising phase II detoxification enzymes, involved in the detoxification of reactive oxygen species. This study evaluated whether daily supplementation with kale juice could modulate levels of plasma antioxidant vitamins and oxidative stress-related parameters. We further examined whether this modulation was affected by combined GSTM1 and T1 polymorphisms. SUBJECTS/METHODS: Totally, 84 subclinical hypertensive patients having systolic blood pressure (BP) over 130 mmHg or diastolic BP over 85 mmHg, received 300 mL of kale juice daily for 6 weeks. Blood samples were drawn before start of study and after completion of 6 weeks. RESULTS: After supplementation, we observed significant decrease in DNA damage and increase in erythrocyte catalase activity in all genotypes. Plasma level of vitamin C was significantly increased in the wild/null and double null genotypes. The plasma levels of β-carotene, erythrocyte glutathione peroxidase activity, and nitric oxide were increased only in the wild/null genotype after kale juice supplementation. CONCLUSIONS: The effect of kale juice was significantly greater in the GSTM1 null genotype and wild/null genotype groups, suggesting possibility of personalized nutritional prescriptions based on personal genetics.
Ascorbic Acid ; Blood Pressure ; Brassica* ; Catalase ; DNA Damage ; Erythrocytes ; Genetics ; Genotype ; Glutathione Peroxidase ; Glutathione Transferase* ; Glutathione* ; Humans ; Hypertension ; Metabolic Detoxication, Phase II ; Multigene Family ; Nitric Oxide ; Oxidative Stress ; Plasma ; Prescriptions ; Reactive Oxygen Species ; Vitamins*

OBJECTIVETo investigate the association between single nucleotide polymorphisms (SNPs) in glutathione peroxidase 1 (GPX-1) gene, rs3448, rs1050450, rs1800668, and rs1987628, and the susceptibility to noise-induced hearing loss (NIHL) among Chinese Han population.

METHODSA case-control study was conducted to investigate the threshold shift of the left ear at 3000 Hz among the workers of Chinese Han population who were exposed to the same level of sound pressure. Two hundred and one (10%) of the subjects with the highest level of threshold shift were recruited in susceptible group, while 202 of (10%) of the subjects with the lowest level of threshold shift were recruited in tolerant group. Targeted occupational health survey and questionnaire survey were performed among these people. For each individual, genome DNA was extracted from 5 ml of fasting peripheral venous blood. Four SNPs (GPX-1 rs3448, rs1050450, rs1800668, and rs1987628) were genotyped by the TaqMan SNP genotyping kit. The main effects of SNPs and the association between NIHL susceptibility and SNPs were analyzed by logistic regression.

RESULTSThe C allele of rs1987628 was a risk factor for NIHL, with an odds ratio (OR) of 2.531 (95%CI: 1.878-3.411) as compared with the T allele. The CC genotype of rs1987628 was more associated with NIHL than the TT genotype (OR = 3.500, 95% CI: 1.984-6.174; adjusted OR = 3.544, 95% CI: 1.974 ∼ 6.364).

CONCLUSIONAmong Chinese Han population, GPX-1 SNP rs1987628 may be associated with the susceptibility to NIHL.

Adult ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Glutathione Peroxidase ; genetics ; Hearing Loss, Noise-Induced ; genetics ; Humans ; Male ; Polymorphism, Single Nucleotide ; Young Adult

OBJECTIVETo assess the association of blood selenium and polymorphism of glutathione peroxidase-1 (GPx-1) genes in patients with Keshan Disease (KD) and provide genetic evidence for KD susceptibility.

METHODSThe levels of whole blood selenium and the activity of GPx-1 were measured with spectrophotometric and enzymatic method among 71 KD patients and 290 controls (including 78 internal controls and 212 external controls). The genotype of GPx-1 at 198 site was analyzed by sequencing and PCR-RFLP. The functions of two GPx-1 variants were studied by rat neonatal cardiomyocytes transfection and expression plasmid.

RESULTSBlood level of selenium in KD patients was (0.8 ± 0.2) µmol/L, the internal controls' was (0.9 ± 0.2) µmol/L, and the external controls' was (1.2 ± 0.2) µmol/L (F = 4.888, P < 0.001).GPx-1 activity of KD patients was (73.0 ± 12.6) × 10(-10)U/RBC, internal controls' was (80.9 ± 9.2) × 10(-10)U/RBC, and external controls' was (115.8 ± 21.1) × 10(-10)U/RBC (F = 5.324, P < 0.001). Those of KD patients were significantly lower than controls. The polymorphism (Pro198Leu) of GPx-1 were identified; the frequency of Pro198Leu of KD patients was 21.1%, the frequency of controls was 10.7% (χ(2) = 5.588, P = 0.018). The level of blood selenium in variant subgroup (Pro198Leu or Leu198Leu) was (0.9 ± 0.2) µmol/L, and its in non-variant subgroup was (1.1 ± 0.3) µmol/L (t = 3.183, P < 0.01); The GPx-1 activity in variant subgroup was (86.1 ± 23.0) × 10(-10)U/RBC, and its in non-variant subgroup was (101.8 ± 25.9) × 10(-10)U/RBC (t = 5.784, P < 0.01). Further analysis revealed a synergistic-multiplicative interaction between presence of GPx-1 codon198 alleles and low blood selenium level. Over-expression of GPx-1 (198Leu) in rat cardiomyocytes caused 30% lower enzyme activity and less response to increasing concentrations of selenium than with over-expression of GPx-1 (198Pro).

CONCLUSIONLow blood selenium in carriers with the 198Leu-susceptible genotype of GPx-1 is associated with low GPx-1 activity, synergistic-multiplicative interaction was found between these two factors. And these two factors may increase the risk of KD.

Adult ; Animals ; Animals, Newborn ; Cardiomyopathies ; genetics ; Case-Control Studies ; Enterovirus Infections ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Glutathione Peroxidase ; genetics ; metabolism ; Humans ; Male ; Middle Aged ; Myocytes, Cardiac ; Polymorphism, Single Nucleotide ; Rats ; Selenium ; blood ; Transfection