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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

Differential expression of HMGB1 and ARG1 in carotid atheroma biopsies of patients with and without symptoms of cerebral embolization.Increased expression of HMGB1 (A; *P = 0.02) but not ARG1 (B; P = 0.82) within carotid atheroma biopsies of symptomatic compared to asymptomatic patients. Data expressed as median and interquartile range with maximum and minimum data points (whiskers) for relative expression.
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pone.0134475.g003: Differential expression of HMGB1 and ARG1 in carotid atheroma biopsies of patients with and without symptoms of cerebral embolization.Increased expression of HMGB1 (A; *P = 0.02) but not ARG1 (B; P = 0.82) within carotid atheroma biopsies of symptomatic compared to asymptomatic patients. Data expressed as median and interquartile range with maximum and minimum data points (whiskers) for relative expression.

Mentions: A gene expression analysis was performed using carotid atheroma biopsies obtained from a group of 18 subjects comprised of 11 and 7 patients with and without recent symptoms of cerebral embolization, respectively (Table 1). Symptomatic patients presented with TIA (N = 7) and ischemic stroke (N = 4). Symptomatic and asymptomatic patients were similar in all of their baseline characteristics (Table 1). 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 (Fig 2). Additionally, we assessed the expression of the HMGB1 gene and found that median relative expression of HMGB1 transcript was ~3-fold upregulated within carotid biopsies of symptomatic compared to asymptomatic patients (P = 0.02; Fig 3A). Finally, median relative expression of the ARG1 transcript was similar within carotid biopsies of symptomatic and asymptomatic patients (P = 0.82; Fig 3B).


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)

Differential expression of HMGB1 and ARG1 in carotid atheroma biopsies of patients with and without symptoms of cerebral embolization.Increased expression of HMGB1 (A; *P = 0.02) but not ARG1 (B; P = 0.82) within carotid atheroma biopsies of symptomatic compared to asymptomatic patients. Data expressed as median and interquartile range with maximum and minimum data points (whiskers) for relative expression.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0134475.g003: Differential expression of HMGB1 and ARG1 in carotid atheroma biopsies of patients with and without symptoms of cerebral embolization.Increased expression of HMGB1 (A; *P = 0.02) but not ARG1 (B; P = 0.82) within carotid atheroma biopsies of symptomatic compared to asymptomatic patients. Data expressed as median and interquartile range with maximum and minimum data points (whiskers) for relative expression.
Mentions: A gene expression analysis was performed using carotid atheroma biopsies obtained from a group of 18 subjects comprised of 11 and 7 patients with and without recent symptoms of cerebral embolization, respectively (Table 1). Symptomatic patients presented with TIA (N = 7) and ischemic stroke (N = 4). Symptomatic and asymptomatic patients were similar in all of their baseline characteristics (Table 1). 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 (Fig 2). Additionally, we assessed the expression of the HMGB1 gene and found that median relative expression of HMGB1 transcript was ~3-fold upregulated within carotid biopsies of symptomatic compared to asymptomatic patients (P = 0.02; Fig 3A). Finally, median relative expression of the ARG1 transcript was similar within carotid biopsies of symptomatic and asymptomatic patients (P = 0.82; Fig 3B).

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