rs662

Chromosome 7
Position 94937445
Gene PON1

CT

42.942.9%

CC

32.932.9%

TT

24.324.3%

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.
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)
Can work both ways ↑↓
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)