|(A;A)||2||higher risk for heart disease, diabetic retinopathy|
|(A;T)||2||higher risk for heart disease, diabetic retinopathy|
|(T;T)||1.8||0.5x lower risk of ovarian cancer|
The snp is suspected of being somewhat confused as an ambiguous flip, because the ReferenceAllele of T has a HapMap freq of 15% in CEU. Also notable is that dbSNP shows RefSNP Alleles: A/C/G/T, and other bits that don't quite fit. While the text below is still of use, it is likely that some of the conclusions are reversed.
rs854560, also known as L55M, is a SNP in the PON1 gene. It codes for amino acid 55 (or 54, depending on the numbering) of the paraoxonase (PON) protein. Variants of this SNP affect levels of PON protein and mRNA and are correlated with Heart disease, aspects of Diabetes including diabetic retinopathy, and trait-anxiety scores.
The apparently more favorable form, rs854560(T), encodes a methionine and lead to elevated levels of paraoxonase, which is generally a good thing. The variant, rs854560(A), encodes an leucine, leading to less paraoxonase activity. [PMID 9011577]
- Note: These alleles are typically reported in the context of the mRNA sense orientation, where the (A) encodes the methionine, and the (T) encodes the leucine. rs854560 as published in dbSNP is from the opposite strand and thus the allele designation is reversed compared to the literature.
[PMID 16926679] rs854560(A) associated with increased common carotid artery intima-media thickness compared to rs854560(T) (p value for trend 0.03), suggesting that variation in the PON1 gene contributes to early atherosclerosis in children with familial hypercholesterolemia.
[PMID 18708400] 274 ovarian epithelial carcinoma cases and 452 controls. rs854560 odds ratio 0.53 (CI: 0.35-0.79; p for allele-dose effect = 0.01) for women carrying the rs854560(T) allele compared with women with the (A;A) genotype
[PMID 17416287] rs854560(A;A) homozygotes experienced a significant increase, while rs854560(T) carriers experienced a non-significant decrease in HDL-Lp-PLA(2) activity (p = 0.030 between groups), upon fluvastatin treatment for 6 months; this may have implications for the treatment of hypercholesterolemia.
[PMID 15060281)] In a study of 461 participants in the HERITAGE cohort (172 African-American, 289 Caucasian), the combination of rs854560 (L55M or PON55) with rs662 (Q192R or PON192) were found to significantly contribute to trait-anxiety scores. The authors also cite another paper, [PMID 12525679], which found that the atypical version of this SNP reduces PON protein and mRNA levels. Which genotypes correlate with increased trait-anxiety scores and/or reduced PON levels is unclear. This paper states that the typical "L" version is TTG, and the "M" substitution is ATG. This may help clear up the ambiguous flip if neighboring base pair information were available from the other sources as well.
[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 20406466] Genetic variants associated with fasting blood lipids in the U.S. population: Third National Health and Nutrition Examination Survey
[PMID 20947215] Paraoxonase-1 polymorphisms in Alzheimer's disease, Parkinson's disease, and AD-PD spectrum diseases
[PMID 21223581] Association analysis of PON2 genetic variants with serum paraoxonase activity and systemic lupus erythematosus
[PMID 22133529] Paraoxonase 1 genetic polymorphisms and susceptibility to breast cancer: A meta-analysis
|Risk||rs854560(C;C) rs854560(G;G) rs854560(N;N) Rs854560(T;T)|
|Alt||rs854560(C;C) rs854560(G;G) rs854560(N;N) Rs854560(T;T)|
|Disease||Coronary artery disease Microvascular complications of diabetes 5 Enzyme activity finding|
|CLNDBN||Coronary artery disease, susceptibility to Microvascular complications of diabetes 5 Enzyme activity finding|
|CLNSRC||OMIM Allelic Variant UniProtKB (protein)|
|CLNACC||RCV000014742.2, RCV000014743.2, RCV000133465.2,|
[PMID 18203168] Folate and one-carbon metabolism gene polymorphisms and their associations with oral facial clefts.
[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 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 19263529] Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach.
[PMID 20018076] Tests for candidate-gene interaction for longitudinal quantitative traits measured in a large cohort.
[PMID 20056567] Childhood brain tumors, residential insecticide exposure, and pesticide metabolism genes.
[PMID 20381198] Lack of association of PON polymorphisms with sporadic ALS in an Italian population.
[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 21543280] Relation between methylmercury exposure and plasma paraoxonase activity in inuit adults from Nunavik.
[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 22798153] Homocysteinylated protein levels in internal mammary artery (IMA) fragments and its genotype-dependence. S-homocysteine-induced methylation modifications in IMA and aortic fragments
[PMID 23356507] Association between paraoxonase gene and stroke in the Han Chinese population
[PMID 24448003] Methylmercury exposure, PON1 gene variants and serum paraoxonase activity in Eastern James Bay Cree adults
[PMID 24477584] Genetic association of IDE, POU2F1, PON1, IL1α and IL1β with type 2 diabetes in Pakistani population
[PMID 22704918] Association of a protective paraoxonase 1 (PON1) polymorphism in Parkinson's disease.
[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 24100645] Association of paraoxonase gene polymorphisms with diabetic nephropathy and retinopathy
[PMID 24972570] PON1 Q192R polymorphism (rs662) is associated with childhood embryonal tumors
[PMID 25902778] Impact of inflammation, gene variants, and cigarette smoking on coronary artery disease risk