Rs854560

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.


 * 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.

Frequency of rs854560(A) allele, and of rs854560(A,A) genotype, appears to increase incidence of diabetic retinopathy.

rs854560(A;A) genotype predicts higher insulin resistance, bodyweight, triglyceride levels, and blood pressure, and therefore cardiovascular risk.

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.

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

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.

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,, 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.

No association between rs854560 and amyotrophic lateral sclerosis was seen in this large meta-analysis.