rs662

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.. However, there are publications that clearly report the opposite. Studies finding greater heart disease risk associated with the Q192 (glutamine) form include: * : 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 * : 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 * : 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: * : 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) * : 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) * : 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. 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 rs1799864(G), rs3025058(A) and rs662(G) were associated with increased risk, and rs1800775(A) with reduced risk of recurrent venous thromboembolism 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, , 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. No association between rs662 and amyotrophic lateral sclerosis was seen in this large meta-analysis.

T;T

see discussion at rs662

C;C

see discussion at rs662