|(A;A)||2||~2x higher risk of of coronary heart disease reported in some studies, but lower risk seen in other studies|
|(A;G)||0.65x lower risk of ovarian cancer; higher risk of coronary heart disease in some studies; somewhat reduced PON catalytic efficiency|
|(G;G)||1.3||Mixed; conflicting results reported related to stroke and CAD|
rs662, also known as Q192R, is a SNP in the PON1 gene. It codes for amino acid 192 of the paraoxonase (PON) protein. Variants of this SNP affect PON catalytic efficiency and are correlated with Heart disease and trait-anxiety scores. The normal form, rs662(A), encodes a glutamine (Q), while the variant, rs662(G), encodes an arginine (R). The general hypothesis is that the glutamine-containing PON1 protein has higher enzymatic activity, leading to lower risk for heart disease.[PMID 8675673]. However, there are publications that clearly report the opposite.
Studies finding greater heart disease risk associated with the Q192 (glutamine) form include:
- [PMID 19778663]: 2009 study involving 10 year follow up study of 800 patients reporting a hazard ratio of 1.71 (CI:1.0 - 2.8, p=0.03) per Q allele
- [PMID 18349088]: 2009 study of ~1400 patients undergoing coronary angiography at the Cleveland Clinic concludes that QQ192 patients have the lowest PON1 activity and have both an increased risk of all-cause mortality (HR 2.05; CI: 1.32-3.18) and of major adverse cardiac events (HR 1.48, CI: 1.09-2.03, p = .01). See also this Table
- [PMID 21170047]: 2011 study of with coronary artery disease patients receiving a stent and taking clopidogrel concluded that QQ192 homozygous individuals had the highest risk for stent thrombosis (OR 3.6; p = 0.0003) and that their PON1 plasma activity, active metabolite plasma concentration and platelet inhibition were all lower compared to RR homozygotes.
Studies finding greater heart disease risk associated with the R192 (arginine) form include:
- [PMID 20856122]: 2010 meta-analysis of 22 eligible studies (totaling 7384 cases/11,074 controls) yields a summary odds ratio for ischemic stroke of 1.10 per G allele (CI: 1.04-1.17)
- [PMID 23625196]: 2013 report on ~200 Saudis concludes that the RR genotype was associated with CAD risk (OR 2.2, CI: 1.4-7.4, p < 0.01)
- [PMID 9215303]: Perhaps the most striking finding with such an association was reported in Japanese patients with non-insulin dependent diabetes mellitus (NIDDM). NIDDM patients with either one or two rs662(G) alleles had a 9 fold higher risk of coronary heart disease compared with rs662(A;A) NIDDM patients.
[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 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 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
|Disease||Coronary artery disease Coronary artery spasm 2 Enzyme activity finding|
|CLNDBN||Coronary artery disease, susceptibility to Coronary artery spasm 2, susceptibility to Enzyme activity finding|
|CLNSRC||OMIM Allelic Variant UniProtKB (protein)|
|CLNACC||RCV000014739.2, RCV000014740.2, RCV000133464.2,|
[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.
[PMID 30128909] Significant association between paraoxonase 1 rs662 polymorphism and coronary heart disease : A meta-analysis in the Chinese population.
[PMID 30173430] [Correlation of the single nucleotide polymorphism rs662 of PON1 with the risk of male infertility].
[PMID 30903418] PON1 is a disease modifier gene in amyotrophic lateral sclerosis: association of the Q192R polymorphism with bulbar onset and reduced survival.