Association between the Advanced Glycosylation End Product-Specific Receptor Gene and Cardiovascular Death in Older MenReport as inadecuate




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Advanced glycosylation end product-specific receptor AGER signaling has been implicated in atherosclerosis. The aim of this study was to evaluate whether a common genetic variation in the AGER gene is associated with cardiovascular CV death. We included 1304 older men who were genotyped for rs1035798:C>T, which is a single nucleotide polymorphism SNP mapped to the third intron of AGER. Cox proportional hazard analysis was used to estimate the association of rs1035798:C>T with CV death. In addition we analyzed total RNA extracted from carotid atherosclerosis biopsies of 18 patients that did or did not have recent symptoms of cerebral embolization by quantitative real-time reverse transcription PCR qRT-PCR. The minor T-allele of rs1035798:C>T was found to be associated with CV death under dominant HR = 1.43, 95% CI: 1.01–2.02, P = 0.04 and recessive HR = 2.05, 95% CI: 1.11–3.81, P = 0.02 models of inheritance even after adjustment for traditional cardiovascular risk factors. No association was found between rs1035798:C>T and non-CV death. qRT-PCR results suggested that median relative expression of AGER isoform 1 and isoform 6 transcripts were approximately 6- P = 0.01 and 2-fold P = 0.02 greater, respectively, within carotid biopsies of symptomatic compared to asymptomatic patients. These data suggest that the minor T allele of rs1035798:C>T represents an independent susceptibility factor for CV death. The expression of AGER isoforms is different in atheroma from patients with recent symptoms. Further studies are needed to investigate if rs1035798:C>T influences the alternative splicing of AGER.



Author: Erik Biros, Corey S. Moran, Paul E. Norman, Graeme J. Hankey, Bu B. Yeap, Osvaldo P. Almeida, Leon Flicker, Richard White, Rhondd

Source: http://plos.srce.hr/



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