{{Rsnum
|rsid=854560
|Gene=PON1
|Chromosome=7
|position=95316772
|Orientation=plus
|ReferenceAllele=T
|MissenseAllele=G
|GMAF=0.2052
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;T)
|geno3=(T;T)
|Gene_s=PON1
}}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|OA=1
}} 

*'''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|9661650}} Frequency of [[rs854560]](A) allele, and of [[rs854560]](A,A) genotype, appears to increase incidence of diabetic retinopathy.

{{PMID|11788650}} [[rs854560]](A;A) genotype predicts higher insulin resistance, bodyweight, triglyceride levels, and blood pressure, and therefore cardiovascular risk.

{{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|OA=1
}} 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|19321847|OA=1
}} No association between [[rs854560]] and amyotrophic lateral sclerosis was seen in this large meta-analysis.

{{omim
|desc=PARAOXONASE ACTIVITY, ELEVATED
|id=168820
|rsnum=854560
|variant=0002
}}

{{PMID Auto
|PMID=19778663
|Title=Paraoxonase variants relate to 10-year risk in coronary artery disease: impact of a high-density lipoprotein-bound antioxidant in secondary prevention
}}

{{PMID Auto
|PMID=20406466
|Title=Genetic variants associated with fasting blood lipids in the U.S. population: Third National Health and Nutrition Examination Survey
|OA=1
}}

{{PMID Auto
|PMID=20947215
|Title=Paraoxonase-1 polymorphisms in Alzheimer's disease, Parkinson's disease, and AD-PD spectrum diseases
|OA=1
}}
{{PMID Auto
|PMID=21223581
|Title=Association analysis of PON2 genetic variants with serum paraoxonase activity and systemic lupus erythematosus
|OA=1
}}

{{PMID Auto
|PMID=22133529
|Title=Paraoxonase 1 genetic polymorphisms and susceptibility to breast cancer: A meta-analysis
}}

{{ClinVar
|rsid=854560
|Reversed=0
|FwdREF=A
|FwdALT=C,G,N,T
|REF=A
|ALT=C,G,N,T
|RSPOS=94946084
|CHROM=7
|GMAF=0.2047
|dbSNPBuildID=86
|SSR=0
|SAO=1
|VP=0x05037800000015051e110100
|GENEINFO=PON1:5444
|GENE_NAME=PON1
|GENE_ID=5444
|WGT=0
|VC=SNV
|CLNALLE=4
|CLNHGVS=NC_000007.13:g.94946084A>T
|CLNSRC=OMIM Allelic Variant
|CLNORIGIN=1
|CLNSRCID=168820.0002
|CLNSIG=255
|CLNCUI=C2674665
|CLNDBN=Coronary artery disease, susceptibility to; Microvascular complications of diabetes 5
|Disease=Coronary artery disease; Microvascular complications of diabetes 5
|CLNACC=RCV000014742.1; RCV000014743.1
|Tags=PM;TPA;PMC;S3D;SLO;VLD;G5;HD;GNO;KGPhase1;KGPilot123;KGPROD;OTHERKG;LSD;OM
|CAF=0.7948; 0.2052
|CLNDSDB=MedGen; MedGen:OMIM
|CLNDSDBID=C1840169; C2674665:612633
|COMMON=1
}}

{{PMID Auto
|PMID=18203168
|Title=Folate and one-carbon metabolism gene polymorphisms and their associations with oral facial clefts.
|OA=1
}}

{{PMID Auto
|PMID=18513389
|Title=New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.
|OA=1
}}

{{PMID Auto
|PMID=18603647
|Title=Functional genetic polymorphisms and female reproductive disorders: Part I: Polycystic ovary syndrome and ovarian response.
|OA=1
}}

{{PMID Auto
|PMID=18618303
|Title=A common haplotype within the PON1 promoter region is associated with sporadic ALS.
|OA=1
}}

{{PMID Auto
|PMID=18936436
|Title=Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994.
|OA=1
}}

{{PMID Auto
|PMID=19041386
|Title=Genetic-epidemiological evidence on genes associated with HDL cholesterol levels: a systematic in-depth review.
|OA=1
}}

{{PMID Auto
|PMID=19104460
|Title=Interaction between PON1 and population density in amyotrophic lateral sclerosis.
}}

{{PMID Auto
|PMID=19131662
|Title=A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations: association of lymphotoxin-alpha in nonhypertensive patients.
|OA=1
}}

{{PMID Auto
|PMID=19263529
|Title=Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach.
|OA=1
}}

{{PMID Auto
|PMID=20018076
|Title=Tests for candidate-gene interaction for longitudinal quantitative traits measured in a large cohort.
|OA=1
}}

{{PMID Auto
|PMID=20056567
|Title=Childhood brain tumors, residential insecticide exposure, and pesticide metabolism genes.
|OA=1
}}

{{PMID Auto
|PMID=20381198
|Title=Lack of association of PON polymorphisms with sporadic ALS in an Italian population.
}}

{{PMID Auto
|PMID=20856122
|Title=Paraoxonase 1 polymorphisms and ischemic stroke risk: A systematic review and meta-analysis.
|OA=1
}}

{{PMID Auto
|PMID=21231776
|Title=C-reactive protein levels are associated with paraoxonase polymorphism L55M in patients undergoing cardiac SPECT imaging.
}}

{{PMID Auto
|PMID=21543280
|Title=Relation between methylmercury exposure and plasma paraoxonase activity in inuit adults from Nunavik.
|OA=1
}}

{{PMID Auto
|PMID=22976839
|Title=NQO1 rs1800566 (C609T), PON1 rs662 (Q192R), and PON1 rs854560 (L55M) polymorphisms segregate the risk of childhood acute leukemias according to age range distribution
}}
{{GET Evidence
|gene=PON1
|aa_change=Leu55Met
|aa_change_short=L55M
|impact=not reviewed
|qualified_impact=Insufficiently evaluated not reviewed
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs854560
|overall_frequency_n=3284
|overall_frequency_d=10758
|overall_frequency=0.305261
|n_genomes=20
|n_genomes_annotated=0
|n_haplomes=25
|n_articles=11
|n_articles_annotated=11
|in_omim=Y
|nblosum100=-3
|autoscore=2
|webscore=N
}}

{{PMID Auto
|PMID=23167629
|Title=Common genetic variants in the myeloperoxidase and paraoxonase genes and the related cancer risk: a review
}}

{{PMID Auto
|PMID=22798153
|Title=Homocysteinylated protein levels in internal mammary artery (IMA) fragments and its genotype-dependence. S-homocysteine-induced methylation modifications in IMA and aortic fragments
}}

{{PMID Auto
|PMID=23356507
|Title=Association between paraoxonase gene and stroke in the Han Chinese population
|OA=1
}}

{{PMID Auto
|PMID=24448003
|Title=Methylmercury exposure, PON1 gene variants and serum paraoxonase activity in Eastern James Bay Cree adults
}}

{{PMID Auto
|PMID=24477584
|Title=Genetic association of IDE, POU2F1, PON1, IL1α and IL1β with type 2 diabetes in Pakistani population
}}
{{PMID Auto
|PMID=22704918
|Title=Association of a protective paraoxonase 1 (PON1) polymorphism in Parkinson's disease.
}}

{{PMID Auto
|PMID=22877234
|Title=Polymorphisms in genes involved in oxidative stress response in patients with sudden sensorineural hearing loss and Meniere's disease in a Japanese population.
|OA=1
}}

{{PMID Auto
|PMID=22884547
|Title=Association analysis of PON polymorphisms in sporadic ALS in a Chinese population.
}}

{{PMID Auto
|PMID=24100645
|Title=Association of paraoxonase gene polymorphisms with diabetic nephropathy and retinopathy
}}

{{PMID Auto
|PMID=24972570
|Title=PON1 Q192R polymorphism (rs662) is associated with childhood embryonal tumors
}}
{{on chip | HumanOmni1Quad}}