• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.803-809
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• 2015

Background: Colorectal cancer (CRC) is a leading cause of cancer-related death. Oxidative DNA damage may contribute to cancer risk and the antioxidant paraoxonase is one endogenous free radical scavenger in the human body which could therefore exert an influeence. Purpose: Aim of this study was to determine the role of serum arylesterase (ARE) and paraoxonase 1(PON1) activities in CRC patients and to find any association between (PON1) Q192R and L55M gene polymorphisms in CRC patients. Also the serum ARE and PON1 activities in CRC patients will be investigated before and after surgery Materials and Methods: This study involved a total of 50 patients with newly diagnosed CRC and 80 healthy controls. PON1 and ARE activities were determined using an enzymatic spectrophotometric method. PON1 Q192R and L55M gene polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based restriction fragment analysis. The restriction enzyme AlwI was used to examine the Q192R polymorphism and Hsp92II for the L55M polymorphism. Results: Significant differences in the PON1 Q192R polymorphism were found between patients and controls. The Q allele was more frequent in the patient group than in controls, while the R allele was more frequent in the controls. Significant differences were found in the L55M polymorphism. Additionally, there were significant differences in L and M allele frequencies (p=0.001). The serum activities of PON1 and ARE were low in QQ and MM genotype. Conclusions: serum PON1 and ARE activities were significantly lower in CRC patients compared to healthy subjects. The R allele may protect against colorectal cancer.

• 한국환경성돌연변이발암원학회지
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• 제21권1호
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• pp.9-13
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• 2001

Essential hypertension is considered to be a multifactorial disease that is influenced not only by environmental factors but also by genetic factors. Genes involved in lipoprotein synthesis, modification and metabolism are candidates for essential hypertension. The purpose of this study was to estimate gene frequencies of paraoxonase/arylesterase (PON1) gene in Korean population and investigate the relationship between genotypes of this gene and essential hypertension or cardiovascular risk factors. In order to estimate the genotype frequencies, Alw I RFLP of PON1 gene was used as genetic marker. There were no significant differences in allele and genotype frequencies between normotensives and essential hypertensives, respectively. However, Alw I RELP of PON1 gene were significantly associated with plasma HDL-cholesterol level in Korean population (one-way ANOVA test, p=0.008). Therefore, our result suggest that this RFLP of PON1 gene may be protective marker on cardiovascular disease in Korean population.

• Journal of Preventive Medicine and Public Health
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• 제38권3호
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• pp.345-350
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• 2005

Objectives : Polycyclic aromatic hydrocarbons (PAHs), which are risk factors for lung cancer, have been reported to induce oxidative DNA damage. The paraoxonase (PON) plays a significant role in the detoxification of a variety of organophosphorous compounds, with paraoxonase-1 (PON1) being one of the endogenous free-radical scavenging systems in the human body. The aim of this case-control study was to investigate the effects of PAH exposure, oxidative stress and the Q192R polymorphism of PON1 genes, and their interactions in the carcinogenesis of lung cancer. Methods : One hundred and seventy seven lung cancer patients and 177 age- and sex-matched controls were enrolled in this study. Each subject was asked to complete a questionnaire concerning their smoking habits and environmental exposure to PAHs. The Q192R genotypes of the PON1 gene was examined, and the concentrations of urinary 1-hydroxypyrene (1-OHP), 2-naphthol and 8-hydroxydeoxyguanosine (8-OH-dG) measured. Results : Cigarette smoking was found to be a significant risk factor for lung cancer. The urinary 8-OH-dG level was higher in the patients, whereas the urinary 1-OHP and 2-naphthol levels were higher in the controls. There was a significant correlation between the urinary levels of 8-OHdG and 1-OHP in both the cases and controls. The PON1 polymorphism was associated with an increased risk of lung cancer. Individuals carrying the Q/Q genotype of the PON1 gene were found to be at higher risk of developing lung cancer. There was a significant correlation between the urinary levels of 8-OH-dG and 1-OHP in those with the PON1 Q/Q genotype. Conclusions : These results lead to the conclusion that PAHs would induce oxidative DNA damage, especially in individuals with the PON1 Q/Q genotype. Therefore, people with the PON1 Q/Q genotype would be more susceptible to lung cancer than those with the R/R or Q/R genotypes of the PON1 gene.

• Asian-Australasian Journal of Animal Sciences
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• 제21권8호
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• pp.1097-1102
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• 2008

Paraoxonase-1 (PON1), like lipoprotein lipase (LPL), plays a key role in the metabolism and physiology of mammalian growth. The objectives of this study were to estimate the allele and genotype frequencies at the PON1/EcoRV and PON1/AluI loci in three genetic groups of beef cattle and to determine associations between these polymorphisms and growth and carcass traits. Genotyping was performed on 30 Angus, 32 Hereford and 26 Simmental. The association analysis was carried out using the GLM procedure of SAS 9.1 and the least squares means of the genotypes were compared by the Tukey's test. Animals with AG genotype at the PON1/EcoRV locus had higher weight at the time of entry into the fattening corrals ($329.97{\pm}6.08kg$) and close to the time of slaughter ($577.56{\pm}8.32kg$) and net meat weight ($275.89{\pm}4.05kg$) and fitted tenderness ($3.10{\pm}0.19kg$) (p<0.05). Animals with AA genotype at the PON1/AluI locus had higher weight at the time of entry ($333.37{\pm}8.93kg$) and slaughter ($576.82{\pm}13.18kg$) and net meat weight ($275.49{\pm}6.43kg$) and average daily gain ($0.68{\pm}0.02kg/d$) (p<0.05). The meat color score was also significantly higher (p<0.05). Between genotypes and breeds, there were significant differences observed except for TBW, REMG, MBS, REA and MCS. As a metabolism gene, genotypes of the SNPs of PON1 gene might be reflecting BFT directly, such as $A_eA_eG_aG_a$ genotype in this experiment.

• Tuberculosis and Respiratory Diseases
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• 제58권5호
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• pp.490-497
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• 2005

연구배경 : Paraoxonase는 산소유리기 제거효소의 하나로서, 유기인제 화합물의 독소제거에 있어서 중요한 역할을 한다. 본 연구에서는 한국인 남성에서 PON1 Q192R 유전자 다형성이 흡연과 관련하여 폐암발생에 미치는 영향을 조사하였다. 대상 및 방법 : 연구대상자는 조직 병리학적으로 폐암으로 새롭게 진단받은 남성 환자 335명과, 이들과 3세 이내에서 연령을 짝지은 동수의 대조군으로 하였다. 직접면접조사를 통하여 인적사항과 직업력 그리고 흡연력, 음주력 등을 조사하였다. TaqMan 실시간 중합 효소 연쇄반응을 이용하여 PON1 유전자 다형성을 확인하고, 폐암과 흡연 그리고 PON1 유전자 다형성 유형 사이의 상호 관련성을 통계적으로 분석하였다. 결 과 : 흡연과 PON1 유전자 Q/Q형이 폐암 발생 위험도를 유의하게 증가시켰다. 흡연자에서 PON1 Q/Q형인 사람이 Q/R 혹은 R/R형인 사람에 비하여 폐암에 대한 교차비(95% 신뢰구간)가 2.56(1.52 - 4.31)으로 폐암발생 위험도가 통계적으로 유의하게 증가하였다. 비흡연자이며 PON1 Q/R 혹은 R/R형인 사람을 비교군으로 하였을 때, 비흡연자이며 PON1 Q/Q형인 군, 흡연자이며 Q/R 혹은 R/R형인 군, 흡연자이며 Q/Q형군으로 이행할수록 대응비는 모든 세포유형에서 유의하게 증가하였다. 특히 흡연자이며 Q/Q형인 사람은 비흡연자이며 PON1 Q/R 혹은 R/R형인 사람에 비하여, 편평세포암종은 53.77(6.55 - 441.14)배, 선암종은 6.25(1.38 - 28.32)배, 소세포암종은 59.94(4.66 - 770.39) 배 더 잘 생기는 것으로 나타났다. 결 론 : 흡연과 PON1 Q/Q형은 폐암의 위험인자이며, 흡연과 PON1 Q/Q형은 조직학적 유형에 관계없이 폐암발생 위험도를 서로 상승적으로 증가시키는 것으로 판단된다.

• 대한한방내과학회지
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• 제31권4호
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• pp.752-762
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• 2010

Objective : In the present study, we investigated genetic distribution of eight single nucleotide polymorphisms of PON1 between Dampness and Phlegm and non Dampness and Phlegm pattern identification(PI) among Korean stroke patients. Materials and Methods : One hundred forty stroke subject without Dampness and Phlegm and fifty eight stroke subjects with Dampness and Phlegm were participated in this study. After informed consents, eight single nucleotide polymorphisms(SNPs) in PON1 of each subjects were identified by DNA sequencing and primer extension method and statistical analysis was performed to determine the significant difference between Dampness and Phlegm and non Dampness and Phlegm groups. Results : Among anthropometric characteristics and blood parameters, waist circumference and total cholesterol were significantly higher in Dampness and Phlegm. Among 8 SNPs of PON1, frequency of M allele and subjects with M allele in L55M SNP were significantly higher in Dampness and Phlegm group (p=0.0032 and p=0.0053, respectively) but subjects with T allele in C-2033T SNP were lower in Dampness and Phlegm group(p=0.0302). Effect of L55M and C-2033T on Dampness and Phlegm were 3.07% and 1.75%, respectively. Conclusion : Our results suggest that L55M SNP in exon and C-2033T in promoter region of PON1 maybe affect to Dampness and Phlegm pattern identification. However, further study should be carried out to find out the detailed mechanism how L55M and C-2033T can affect Dampness and Phlegm stroke patients.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4457-4463
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• 2015

Common genetic variation Q192R in the paraoxonase 1 (PON1) gene has been considered to be implicated in the development of many cancers. Nevertheless, results from the related studies were inconsistent. To elucidate the association, we performed a meta-analysis for 8,112 cases and 10,037 controls from 32 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association by STATA 12.0 software. Overall, we revealed that the PON1-192R allele was associated with a reduced risk of the overall cancers. Moreover, in the stratified analysis by cancer types (breast cancer, prostate cancer, brain cancer etc.), the results showed that PON1-192R allele was associated with a decreased risk in breast cancer (R vs Q: OR=0.605, 95% CI=0.378-0.967, $P_{heterogeneity}=0.000$; RR vs QQ: OR=0.494, 95% CI=0.275-0.888, $P_{heterogeneity}=0.002$; RQ vs QQ: OR=0.465, 95% CI=0.259-0.835, $P_{heterogeneity}=0.000$; and RR+RQ vs QQ: OR=0.485, 95% CI=0.274-0.857, $P_{heterogeneity}=0.000$), and associated with prostate cancer in homozygote (RR vs QQ: OR=0.475, 95% CI=0.251-0.897, $P_{heterogeneity}=0.001$) and recessive models (RR vs RQ+QQ: OR=0.379, 95% CI=0.169-0.853, $P_{heterogeneity}=0.000$), while an increased risk was identified in lymphoma (R vs Q: OR=1.537, 95% CI=1.246-1.896, $P_{heterogeneity}=0.944$; RR vs QQ: OR=2.987, 95% CI=1.861-4.795, $P_{heterogeneity}=0.350$; RR+RQ vs QQ: OR=1.354, 95% CI=1.021-1.796, $P_{heterogeneity}=0.824$; and RR vs RQ+QQ: OR=2.934, 95% CI=1.869-4.605, $P_{heterogeneity}=0.433$), and an increased risk in prostate cancer under heterozygote comparison (RQ vs QQ: OR=1.782, 95% CI=1.077-2.950, $P_{heterogeneity}=0.000$) and dominant models (RR+RQ vs QQ: OR=1.281, 95% CI=1.044-1.573, $P_{heterogeneity}=0.056$). When subgroup analysis that performed by the control source (hospital based or population based), a decreased risk of the overall cancers was revealed by homozygote (RR vs QQ: OR=0.601, 95% CI=0.366-0.987, $P_{heterogeneity}=0.000$) and dominant models (RR vs RQ+QQ: OR= 0.611, 95% CI=0.384-0.973, $P_{heterogeneity}=0.000$) in hospital based group. Stratifying by ethnicity, a significantly reduced risk of the overall cancers under allele contrast model (R vs Q: OR=0.788, 95% CI=0.626-0.993, $P_{heterogeneity}=0.000$) was uncovered in Caucasian. In summary, these findings suggested that PON1 Q192R polymorphism was associated with a reduced risk of the overall cancers, nevertheless, it might increase cancer susceptibility of prostate and lymphoma risk. Large well-designed epidemiological studies will be continued on this issue of interest.