Chromosome | 7 |
Position | 94937445 |
Gene | PON1 |
CT | 42.9 | 42.9% |
CC | 32.9 | 32.9% |
TT | 24.3 | 24.3% |
Breakdown:
The T allele is associated with:
- TT = 2.3X higher risk of coronary heart disease
- TT = Increased risk of vascular dementia (Ref)
- TT = Increased risk of kidney disease
- TT = Ischemic heart disease (Ref).
- TT = Kidney disease (Ref).
- TT or TC associated with Male infertility (Ref).
- T is usually associated with decreased blood levels of PON1 (Ref, Ref) and lower PON1 activity (Ref), which explains why CT or CC have a 43% lower risk of breast cancer in one study (Ref).
- TT breaks down oxidized LDL better (Ref, Ref), whereas CC detoxes most organophosphate (including chlorpyrifos oxon , diazoxon, sarin, and soman) pesticides better (Ref) (Ref, Ref).
- T is 2X more efficient at breaking down oxidized lipids (such as oxLDL) (Ref )
- The T encodes a glutamine (“Q”), C encodes an arginine (“R”) (Ref).
The C allele is associated with:
- Prenatally pesticide-exposed children carrying the C allele had higher abdominal circumference, body fat content, BMI, blood pressure, leptin and IGF-1 at school age than unexposed children. The effects were related to the prenatal exposure level. For children with TT , none of the variables was affected by prenatal pesticide exposure. Only exposed children with the C allele developed adverse heart disease risk profiles thought to be associated with the C allele. (Ref)
- CC = Increased risk of Alzheimers Disease (Ref)
- CC = Increased anxiety (Ref).
- C; Heart disease. A weak association between the C allele and increased heart disease risk has been confirmed in most case-control studies, and is supported by meta-analyses (Ref, Ref, Ref, Ref). In combination with low serum HDL and the CC markedly increased the risk of heart disease (Ref).
- Increased diabetes risk (CC) (Ref). Type 2 diabetics with either one or two C alleles had a 9 fold higher risk of heart disease compared with TT (Ref).
- The C allele results in eight times more efficient enzyme activity than T concerning some organophosphates) (Ref).
- C lowered arylesterase activity in people with Autism, but not in healthy people (Ref).
Research articles:
[PMID 18708400] 274 ovarian epithelial carcinoma cases and 452 controls. rs662 odds ratio 0.65 (CI: 0.44-0.95; p for allele-dose effect = 0.03) for ovarian cancer for women carrying the rs662(A) allele compared with women with the (G;G) genotype
[PMID 19263529] rs1799864(G), rs3025058(A) and rs662(G) were associated with increased risk, and rs1800775(A) with reduced risk of recurrent venous thromboembolism
[PMID 15060281)] In a study of 461 participants in the HERITAGE cohort (172 African-American, 289 Caucasian), the combination of rs662 with rs854560 was found to significantly contribute to trait-anxiety scores. The high trait-anxiety group included “significantly more subjects homozygous to the Alzheimer’s disease- predictive PON192 variant.” The authors also cite another paper, [PMID 12525679], which found that this SNP affects PON’s catalytic efficiency. From the context, it appears that it is the “R” variant, or rs662(G), which corresponds to the higher trait-anxiety scores and reduced catalytic efficiency, though this is less explicitly stated than one might hope.
[PMID 19321847] No association between rs662 and amyotrophic lateral sclerosis was seen in this large meta-analysis.
[PMID 19651761] The paraoxonase (PON1) Q192R polymorphism is not associated with poor health status or depression in the ELSA or INCHIANTI studies
[PMID 19357718] Genetic polymorphisms of paraoxonase-1 are associated with chronic kidney disease in Japanese women
[PMID 19778663] Paraoxonase variants relate to 10-year risk in coronary artery disease: impact of a high-density lipoprotein-bound antioxidant in secondary prevention
[PMID 20947215] Paraoxonase-1 polymorphisms in Alzheimer’s disease, Parkinson’s disease, and AD-PD spectrum diseases
[PMID 21122033] Leukoaraiosis is associated with genes regulating blood-brain barrier homeostasis in ischaemic stroke patients
[PMID 21223581] Association analysis of PON2 genetic variants with serum paraoxonase activity and systemic lupus erythematosus
[PMID 20488557] Decreased serum arylesterase activity in autism spectrum disorders
[PMID 21567207] Tetra primer ARMS-PCR relates folate/homocysteine pathway genes and ACE gene polymorphism with coronary artery disease
[PMID 22133529] Paraoxonase 1 genetic polymorphisms and susceptibility to breast cancer: A meta-analysis
[PMID 22187169] A New PCR Method: One Primer Amplification of PCR-CTPP Products
[PMID 22206979] Genetic variants in antioxidant genes are associated with sperm DNA damage and risk of male infertility in a Chinese population
[PMID 22615820] Paraoxonase 1 Polymorphism and Prenatal Pesticide Exposure Associated with Adverse Cardiovascular Risk Profiles at School Age
[PMID 18034366] Lack of replication of genetic associations with human longevity.
[PMID 18194558] A hierarchical and modular approach to the discovery of robust associations in genome-wide association studies from pooled DNA samples.
[PMID 18203168] Folate and one-carbon metabolism gene polymorphisms and their associations with oral facial clefts.
[PMID 18282109] Adaptations to climate in candidate genes for common metabolic disorders.
[PMID 18513389] New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.
[PMID 18034366] Lack of replication of genetic associations with human longevity.
[PMID 18194558] A hierarchical and modular approach to the discovery of robust associations in genome-wide association studies from pooled DNA samples.
[PMID 18203168] Folate and one-carbon metabolism gene polymorphisms and their associations with oral facial clefts.
[PMID 18282109] Adaptations to climate in candidate genes for common metabolic disorders.
[PMID 18513389] New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.
[PMID 18603647] Functional genetic polymorphisms and female reproductive disorders: Part I: Polycystic ovary syndrome and ovarian response.
[PMID 18618303] A common haplotype within the PON1 promoter region is associated with sporadic ALS.
[PMID 18682580] Oxidative response gene polymorphisms and risk of adult brain tumors.
[PMID 18787196] Segment-specific genetic effects on carotid intima-media thickness: the Northern Manhattan study.
[PMID 18936436] Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994.
[PMID 19041386] Genetic-epidemiological evidence on genes associated with HDL cholesterol levels: a systematic in-depth review.
[PMID 19104460] Interaction between PON1 and population density in amyotrophic lateral sclerosis.
[PMID 19131662] A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations: association of lymphotoxin-alpha in nonhypertensive patients.
[PMID 19276285] Associations between single nucleotide polymorphisms in double-stranded DNA repair pathway genes and familial breast cancer.
[PMID 19587357] A systematic meta-analysis of genetic association studies for diabetic retinopathy.
[PMID 20031584] Genetics of atherothrombotic and lacunar stroke.
[PMID 20056567] Childhood brain tumors, residential insecticide exposure, and pesticide metabolism genes.
[PMID 20140262] Maternal and fetal genetic associations of PTGER3 and PON1 with preterm birth.
[PMID 20381198] Lack of association of PON polymorphisms with sporadic ALS in an Italian population.
[PMID 20616999] Usefulness of Mendelian randomization in observational epidemiology.
[PMID 20856122] Paraoxonase 1 polymorphisms and ischemic stroke risk: A systematic review and meta-analysis.
[PMID 21231776] C-reactive protein levels are associated with paraoxonase polymorphism L55M in patients undergoing cardiac SPECT imaging.
[PMID 21438666] Association of PON1 and APOA5 gene polymorphisms in a cohort of Indian patients having coronary artery disease with and without type 2 diabetes.
[PMID 21543280] Relation between methylmercury exposure and plasma paraoxonase activity in inuit adults from Nunavik.
[PMID 21685174] Paraoxonase-1 Q192R polymorphism and antiplatelet effects of clopidogrel in patients undergoing elective coronary stent placement.
[PMID 22520065] Influence of the paraoxonase-1 Q192R genetic variant on clopidogrel responsiveness and recurrent cardiovascular events: a systematic review and meta-analysis.
[PMID 22976839] NQO1 rs1800566 (C609T), PON1 rs662 (Q192R), and PON1 rs854560 (L55M) polymorphisms segregate the risk of childhood acute leukemias according to age range distribution
[PMID 23167629] Common genetic variants in the myeloperoxidase and paraoxonase genes and the related cancer risk: a review
[PMID 23391848] OLR1 , PON1 and MTHFR Gene Polymorphisms, Conventional Risk Factors and the Severity of Coronary Atherosclerosis in a Chinese Han Population
[PMID 23356507] Association between paraoxonase gene and stroke in the Han Chinese population
[PMID 23651475] Polymorphisms in xenobiotic metabolizing genes (EPHX1, NQO1 and PON1) in lymphoma susceptibility: a case control study
[PMID 24206655] Association of a polymorphism in PON-1 gene with steroid-induced osteonecrosis of femoral head in Chinese Han population
[PMID 23903878] Prenatal methylmercury exposure and genetic predisposition to cognitive deficit at age 8 years
[PMID 24448003] Methylmercury exposure, PON1 gene variants and serum paraoxonase activity in Eastern James Bay Cree adults
[PMID 22877234] Polymorphisms in genes involved in oxidative stress response in patients with sudden sensorineural hearing loss and Meniere’s disease in a Japanese population.
[PMID 22884547] Association analysis of PON polymorphisms in sporadic ALS in a Chinese population.
[PMID 23625196] The Q192R polymorphism of the paraoxonase 1 gene is a risk factor for coronary artery disease in Saudi subjects.
[PMID 24833785] Investigation of a PON1 gene polymorphism (rs662 polymorphism) as predictor of subclinical atherosclerosis in patients with rheumatoid arthritis
[PMID 24100645] Association of paraoxonase gene polymorphisms with diabetic nephropathy and retinopathy
[PMID 24903972] Genetic predisposition to calcific aortic stenosis and mitral annular calcification
[PMID 24918121] Association between PON1 rs662 polymorphism and coronary artery disease
[PMID 24965284] Synergistic Epistasis of Paraoxonase 1 (rs662 and rs85460) and Apolipoprotein E4 Genes in Pathogenesis of Alzheimer’s Disease and Vascular Dementia
[PMID 24972570] PON1 Q192R polymorphism (rs662) is associated with childhood embryonal tumors
[PMID 24981930] Relationships between PON1 Q192R polymorphism and clinical outcome of antiplatelet treatment after percutaneous coronary intervention: a meta-analysis
[PMID 25500007] Q192R Polymorphism of Paraoxonase 1 Gene Associated with Insulin Resistance in Mexican Children
[PMID 25741997] Interactions between Paraoxonase 1 Genetic Polymorphisms and Smoking and Their Effects on Oxidative Stress and Lung Cancer Risk in a Korean Population
[PMID 25746376] Interaction effects between Paraoxonase 1 variants and cigarette smoking on risk of coronary heart disease in a Singaporean Chinese population
[PMID 25935173] Genetic polymorphisms in paraoxonase 1 and G protein-coupled receptor 77, and the risk of glucose-6-phosphate dehydrogenase deficiency in a Saudi population
[PMID 26091975] Paraoxonase-1 and oxidized lipoprotein lipids. The Cardiovascular Risk in Young Finns Study
[PMID 26632904] Association of Paraoxonase 1 Gene Polymorphisms With the Risk of Hepatitis B Virus-related Liver Diseases in a Guangxi Population: A Case-control Study.
[PMID 26870959] Association of PON1, P2Y12 and COX1 with Recurrent Ischemic Events in Patients with Extracranial or Intracranial Stenting.
[PMID 28027289] Paraoxonase-1 (PON1) rs662 Polymorphism and Its Association with Serum Lipid Levels and Longevity in the Bama Zhuang Population.
EXPRESSION CONTROL
Mitigate things that decrease PON1:
- Omega-6s such as linolenic acid and arachidonic acid decrease PON1 (Ref).
- Low grade inflammation will decrease PON1, so you should fix general inflammation (Ref).
- PON1 in human blood is inactivated by oxidized LDL and preserved by antioxidants (Ref), so taking care of oxidative stress in general is a good idea.
Activating PPAR gamma increases the synthesis and release of PON1 from the liver (Ref).
Ways to optimise PON1 function:
- Vitamin E
- Mediterranean Diet (Ref),
- Extra Virgin Olive Oil (Ref),
- Fish oil/DHA (Ref, Ref),
- Broccoli sprouts/Sulforaphane (Ref),
- Allyl isothiocyanate (found in mustard, radish, wasabi) (Ref)
- Curcumin (Ref),
- EGCG (Ref),
- Aspirin (Ref)
- Quercetin (Ref),
- Pomegranate (Ref),
- Resveratrol (Ref),
- Berberine (Ref)
- Glutathione (Ref),
- Statins (Ref)
- Other: Sumac (R), Atorvastatin (Ref),
Compounds that Decrease PON1 activity ↓
Carbon Tetrachloride | Decreases abundance , Decreases reaction | (R) , (R) |
Soman | Decreases activity , Decreases reaction | (R) , (R) | |
Copper Sulfate | Decreases activity , Decreases reaction | (R) , (R) | |
Dichlorvos | Decreases activity , Decreases reaction | (R) , (R) | |
Organophosphorus Compounds | Decreases expression | (R) |
Sarin | Decreases activity , Decreases reaction | (R) , (R) | |
Cyclohexyl methylphosphonofluoridate | Decreases response to substance | (R) | |
Polyethylene Glycols | Decreases activity , Decreases reaction | (R) , (R) |
Iron | Decreases expression , Decreases reaction | (R) , (R) | |
Trans-10,cis-12-conjugated linoleic acid | Decreases activity , Decreases reaction | (R) , (R) |
Palmitoleic acid | Decreases activity , Decreases reaction | (R) , (R) |
Hydroxymercuribenzoates | Decreases activity , Decreases reaction | (R) | |
1,2-dioleoyl-sn-glycero-3-phosphoglycerol | Decreases activity , Decreases reaction | (R) , (R) | |
Pesticides | Decreases activity | (R) |
Anthra(1,9-cd)pyrazol-6(2H)-one | Decreases expression , Decreases reaction | (R) , (R) | |
Tetrachlorodibenzodioxin | Decreases expression | (R) | |
Rutin | Decreases expression , Decreases reaction | (R) , (R) | |
Plant Extracts | Decreases activity , Decreases reaction | (R) , (R) | |
Vitamin E | Decreases activity , Decreases reaction | (R) , (R) | |
Chenodeoxycholic Acid | Decreases expression , Decreases reaction | (R) , (R) |
Methyl Parathion | Decreases activity , Decreases expression | (R) , (R) |
Selenium | Decreases activity , Decreases reaction | (R) , (R) | |
1,2-oleoylphosphatidylcholine | Decreases activity , Decreases reaction | (R) , (R) |
Perfluorooctanoic acid | Decreases expression | (R) |
Methylmercury Compounds | Decreases activity | (R) ( R) |
Butylated Hydroxytoluene | Decreases expression , Decreases reaction | (R) | |
Tabun | Decreases response to substance | (R) |
Tempol | Decreases activity , Decreases reaction | (R) , (R) | |
Glutathione | Decreases abundance , Decreases reaction | (R) , (R) |
Cholesterol | Decreases chemical synthesis | (R) | |
Erucic acid | Decreases activity , Decreases reaction | (R) , (R) |
VX | Decreases response to substance | (R) | |
Environmental Pollutants | Decreases activity | (R) |
4-hydroxymercuribenzoate | Decreases activity | (R) |
Taurocholic Acid | Decreases expression | (R) |
Vorinostat | Decreases expression | (R) | |
1,4-bis(2-(3,5-dichloropyridyloxy))benzene | Decreases expression | (R) | |
Ampicillin | Decreases activity | (R) | |
Cholic Acid | Decreases expression | (R) | |
Ciprofloxacin | Decreases activity | (R) | |
Clofibrate | Decreases expression | (R) | |
Clofibric Acid | Decreases expression | (R) | |
Estrogen | Decreases expression | (R) |
Mercury | Decreases activity | (R) |
Propylthiouracil | Decreases activity | (R) | |
Silicon Dioxide | Decreases expression | (R) |
Clindamycin phosphate | Decreases activity | (R) |
Hydrazine | Decreases expression | (R) | |
Naphthalene | Decreases expression | (R) | |
Panobinostat | Decreases expression | (R) | |
Rosiglitazone | Decreases expression | (R) | |
Soot | Decreases expression | (R R) | |
Sodium Selenite | Decreases expression | (R) | |
Reactive Oxygen Species | Decreases activity | (R) | |
Phenytoin | Decreases expression | (R) | |
Fumonisin B1 | Decreases expression | (R) | |
Furan | Decreases expression | (R) | |
2,5,2′,5′-tetrachlorobiphenyl | Decreases expression | (R) | |
Titanium dioxide | Decreases expression | (R) | |
Phenylmercuric Acetate | Decreases expression | (R) | |
Ozone | Decreases expression | (R) | |
Nandrolone decanoate | Decreases activity | (R) | |
2,3-pentanedione | Decreases expression | (R) | |
Ochratoxin A | Decreases expression | (R) | |
Nicotine | Decreases activity | (R) | |
Trichostatin A | Decreases expression | (R) | |
Methotrexate | Decreases expression | (R) | |
Endosulfan | Decreases expression | (R) | |
Edetic Acid | Decreases activity | (R) | |
Dietary Fats, Unsaturated | Decreases expression | (R) | |
Cyclosporine | Decreases expression | (R) | |
1,2-dithiol-3-thione | Decreases expression | (R) | |
Sodium arsenite | Decreases expression | (R) | |
Bisphenol A | Decreases expression | (R) | |
Ciprofibrate | Decreases expression | (R) | |
BIRB 796 | Decreases expression | (R) | |
Bexarotene | Decreases expression | (R) | |
Allyl sulfide | Decreases expression | (R) | |
Tamoxifen | Decreases expression | (R) |
Increase activity ↑
Paraoxon | Increases metabolic processing , Increases reaction | (R) , (R) |
3,4,5,3′,4′-pentachlorobiphenyl | Increases expression | (R) | |
Cholesterol, HDL | Increases activity | (R) | |
Insecticides | Increases mutagenesis | (R) | |
Calcium | Increases stability | (R) | |
Oleic Acid | Increases stability | (R) | |
Phenyl acetate | Increases hydrolysis | (R) |
Chlorpyrifos | Increases activity | (R) | |
Cadmium | Increases metabolic processing , Increases reaction | (R) , (R) |
Aspirin | Increases activity | (R) | |
Diethylnitrosamine | Increases expression | (R) | |
CLA | Increases activity | (R) |
Calcium Chloride | Increases hydrolysis , Increases reaction | (R) , (R) |
Atorvastatin Calcium | Increases activity | (R), ( R) |
Dieldrin | Increases expression | (R) |
Benzo(a)pyrene | Increases expression | (R) |
Acrolein | Increases metabolic processing | (R) |
4-nitrophenyl acetate | Increases hydrolysis | (R) | |
Oxygen | Increases reaction | (R) | |
Nitroaspirin | Increases activity | (R) | |
Parathion | Increases metabolic processing | (R) |
Dexamethasone | Increases expression | (R) | |
Plant Preparations | Increases activity | (R) |
Salicylates | Increases activity | (R) |
Sodium bichromate | Increases expression | (R) | |
2,4,5,2′,4′,5′-hexachlorobiphenyl | Increases expression | (R) | |
2-oxo-clopidogrel | Increases hydrolysis | (R) | |
4-nitrophenol | Increases chemical synthesis | (R) | |
Acetylcysteine | Increases activity | (R) | |
Cisplatin | Increases expression | (R) | |
Coumarins | Increases hydrolysis | (R) | |
Cyclophosphamide | Increases activity | (R) | |
Fatty Acids, Monounsaturated | Increases activity | (R) | |
Fenofibrate | Increases expression | (R) | |
Lactones | Increases hydrolysis | (R) | |
Metformin | Increases response to substance | (R) | |
Methimazole | Increases activity | (R) | |
N-nitrosomorpholine | Increases expression | (R) | |
Obidoxime Chloride | Increases hydrolysis | (R) | |
Olive Oil | Increases activity | (R) | |
Omacor | Increases expression | (R) | |
Phenylacetates | Increases metabolic processing | (R) | |
Plant Oils | Increases activity | (R) | |
Polychlorinated Biphenyls | Increases expression | (R) | |
Polycyclic Hydrocarbons, Aromatic | Increases response to substance | (R) | |
Progesterone | Increases expression | (R) | |
Rifampin | Increases expression | (R) | |
S-(N,N-diethylaminoethyl) isobutyl methylphosphothiolate | Increases hydrolysis | (R) | |
Thiobarbituric Acid Reactive Substances | Increases abundance | (R) | |
Benzo(k)fluoranthene | Increases expression | (R) | |
Bifenthrin | Increases expression | (R) | |
Chromic chloride | Increases expression | (R) | |
Decabromobiphenyl ether | Increases expression | (R) | |
Decan-4-olide | Increases hydrolysis | (R) | |
Entinostat | Increases expression | (R) | |
Flavone | Increases expression | (R) | |
Lipopolysaccharide, E coli O55-B5 | Increases expression | (R) | |
Methylmercuric chloride | Increases expression | (R) | |
Naringenin | Increases expression | (R) | |
Orlistat | Increases activity | (R) (R) | |
Propionaldehyde | Increases expression | (R) | |
1,2-dilauroylphosphatidylcholine | Increases activity | (R) |
Copper | Increases metabolic processing | (R) | |
Phenylacetic acid | Increases hydrolysis | (R) | |
Simvastatin | Increases expression | (R) | |
Resveratrol | Increases expression | (R) |
Oximes | Increases hydrolysis , Increases reaction | (R) , (R) | |
Hydrogen Peroxide | Increases hydrolysis | (R) |
Quercetin | Increases expression | (R) |
Ethyl 4-nitrophenyl methylphosphonate | Increases hydrolysis , Increases reaction | (R) , (R) | |
Selenic Acid | Increases expression | (R) | |
4-nitrophenyl 2-propylmethylphosphonate | Increases hydrolysis , Increases reaction | (R) , (R) | |
Linoleic Acid | Increases hydrolysis | (R) | |
Cumene hydroperoxide | Increases oxidation | (R) | |
2-hydroxyquinoline | Increases hydrolysis | (R) |
Isoflurophate | Increases hydrolysis | (R) | |
Methylcholanthrene | Increases expression | (R) |
Pitavastatin | Increases expression | (R) | Substances of Biological Interest |
Ferrous sulfate | Increases hydrolysis | (R) | |
Fluvastatin | Increases hydrolysis | (R) | |
Pyruvaldehyde | Increases hydrolysis | (R) | |
4-hydroxy-2-nonenal | Increases hydrolysis | (R) | |
Arachidonic Acid | Increases hydrolysis | (R) | |
Nickel | Increases metabolic processing | (R) | |
Mevalonic Acid | Increases expression | (R) | |
Lead | Increases metabolic processing | (R) | |
Hypochlorous Acid | Increases reaction | (R) | |
7-ketocholesterol | Increases expression | (R) | |
Pirinixic acid | Increases activity | (R) | |
Sulfhydryl Compounds | Increases reaction | (R) | |
Zinc | Increases metabolic processing | (R) |
Farnesyl pyrophosphate | Increases expression | (R) | |
1,2-dipalmitoylphosphatidylglycerol | Increases reaction | (R) | |
Lysophosphatidylglycerol | Increases hydrolysis | (R) | |
Lysophosphatidylinositol | Increases hydrolysis | (R) | |
Homocysteine | Increases abundance | (R) |
Manganese | Increases metabolic processing | (R) |
Malondialdehyde | Increases abundance | (R) |
Geranylgeranyl pyrophosphate | Increases expression | (R) |
Plicamycin | Increases expression | (R) |
Squalene | Increases expression | (R) | |
Methionine | Increases abundance | (R) |