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Association between the Advanced Glycosylation End Product-Specific Receptor Gene and Cardiovascular Death in Older Men.

Biros E, Moran CS, Norman PE, Hankey GJ, Yeap BB, Almeida OP, Flicker L, White R, Jones R, Golledge J - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Australia.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier analysis illustrating probability of death in relation to AGER rs1035798:C>T genotypes.The minor (T) allele of rs1035798:C>T was associated with an increased probability of CV death under a dominant (A; P = 0.04) and recessive (B; P = 0.03) model of inheritance. The T-allele had no association with the probability of non-CV death under a dominant (C; P = 0.95) and recessive (D; P = 0.87) model of inheritance.
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pone.0134475.g001: Kaplan-Meier analysis illustrating probability of death in relation to AGER rs1035798:C>T genotypes.The minor (T) allele of rs1035798:C>T was associated with an increased probability of CV death under a dominant (A; P = 0.04) and recessive (B; P = 0.03) model of inheritance. The T-allele had no association with the probability of non-CV death under a dominant (C; P = 0.95) and recessive (D; P = 0.87) model of inheritance.

Mentions: The association of rs1035798:C>T with CV death was further examined using Kaplan-Meier analysis. The results are shown in Fig 1. An increased probability of CV death in relation to rs1035798:C>T minor (T) allele was seen under a dominant (P = 0.04; Fig 1A) and recessive (P = 0.03; Fig 1B) model of inheritance. The minor T-allele of rs1035798:C>T had no association with the probability of non-CV death (P>0.05; Fig 1C and 1D).


Association between the Advanced Glycosylation End Product-Specific Receptor Gene and Cardiovascular Death in Older Men.

Biros E, Moran CS, Norman PE, Hankey GJ, Yeap BB, Almeida OP, Flicker L, White R, Jones R, Golledge J - PLoS ONE (2015)

Kaplan-Meier analysis illustrating probability of death in relation to AGER rs1035798:C>T genotypes.The minor (T) allele of rs1035798:C>T was associated with an increased probability of CV death under a dominant (A; P = 0.04) and recessive (B; P = 0.03) model of inheritance. The T-allele had no association with the probability of non-CV death under a dominant (C; P = 0.95) and recessive (D; P = 0.87) model of inheritance.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4520603&req=5

pone.0134475.g001: Kaplan-Meier analysis illustrating probability of death in relation to AGER rs1035798:C>T genotypes.The minor (T) allele of rs1035798:C>T was associated with an increased probability of CV death under a dominant (A; P = 0.04) and recessive (B; P = 0.03) model of inheritance. The T-allele had no association with the probability of non-CV death under a dominant (C; P = 0.95) and recessive (D; P = 0.87) model of inheritance.
Mentions: The association of rs1035798:C>T with CV death was further examined using Kaplan-Meier analysis. The results are shown in Fig 1. An increased probability of CV death in relation to rs1035798:C>T minor (T) allele was seen under a dominant (P = 0.04; Fig 1A) and recessive (P = 0.03; Fig 1B) model of inheritance. The minor T-allele of rs1035798:C>T had no association with the probability of non-CV death (P>0.05; Fig 1C and 1D).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Australia.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus