The rs12526453 Polymorphism in an Intron of the PHACTR1 Gene and Its Association with 5-Year Mortality of Patients with Myocardial Infarction.

PLoS One 2015 18;10(6):e0129820. Epub 2015 Jun 18.

Department of Cardiology, Medical University of Bialystok, Bialystok, Poland.

Objective: The rs12526453 (C/G) is a single nucleotide polymorphism in an intron of the PHACTR1 gene (phosphatase and actin regulator 1). The C allele is associated with increased risk of coronary artery disease in an unknown mechanism. We investigated its association with long-term overall mortality in patients with ST-elevation myocardial infarction (STEMI) treated invasively.

Methods: Two independent groups of patients with STEMI were analyzed: a derivation group (n= 638) and a validation one (n=348). Genotyping was performed with the TaqMan method. The analyzed end-point was total long term mortality. Additionally, transcriptomic analysis was performed in mononuclear blood leukocytes from rs12526453 CC monozygotes or G allele carriers.

Results: In the study group (mean age 62.3 ± 11.9 years; 24.9% of females, n=159), percentages of CC, CG, and GG genotypes were 45.3% (n=289), 44.7% (n=285), and 10% (n=64), respectively. In the 5-year follow-up 105 patients died (16.46%). CC homozygotes had significantly lower mortality compared to other genotypes: 13.1% (n=38) vs. 18.3% in G-allele carriers (n=67), (p=0.017, Cox`s F test). In the validation group 47 patients died within 3 years (13.5%). We confirmed lower mortality of CC homozygotes: 10.1 % (n=18) vs. 16.95% in G-allele carriers (n=29), (p=0.031, Cox`s F test). Transcriptomic analysis revealed a markedly higher expression of NLRP-2 in CC homozygotes.

Conclusions: The rs12526453 CC homozygotes (previously associated with increased risk of myocardial infarction) showed, in 2 independent samples, better long-term survival. The finding of such high effect size, after appropriate validation, could potentially be translated into clinical practice.

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0129820PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472810PMC
April 2016
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