Limits...
Association of four genetic polymorphisms of AGER and its circulating forms with coronary artery disease: a meta-analysis.

Peng F, Hu D, Jia N, Li X, Li Y, Chu S, Zhu D, Shen W, Lin J, Niu W - PLoS ONE (2013)

Bottom Line: For example, under dominant model, having -429C allele increased the odds of developing CAD in diabetic patients by 1.22-fold (95% confidence interval (95% CI) 0.99-1.51; P = 0.06; I (2) = 6.7%) compared with that of overall estimate of 1.15-fold (95% CI: 0.97-1.36; P = 0.111; I (2) = 18.0%).Circulating sRAGE levels were non-significantly lower in CAD patients than in controls, whereas this reduction was totally and significantly reversed in CAD patients with diabetes mellitus (weighted mean difference: 185.71 pg/ml; 95% CI: 106.82 to 264.61 pg/ml).Practically, circulating esRAGE might be a powerful negative predictor for the development of CAD.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

ABSTRACT

Background: Considerable efforts have been devoted to evaluating the association of the receptor for advanced glycation end-products (gene AGER and protein: RAGE) genetic variants to coronary artery disease (CAD); the results, however, are often irreproducible. To generate more information, we sought to explore four common polymorphisms of AGER and its circulating forms associated with the risk of CAD via a meta-analysis.

Methodology/principal findings: Articles were identified by searching PubMed, EMBASE, Wanfang and CNKI databases before March 2013. Qualified articles had case-control designs and investigated AGER four polymorphisms (T-429C, T-374A, Gly82Ser, G1704A) or circulating soluble RAGE (sRAGE) or endogenous secretory RAGE (esRAGE) levels associated with CAD. Twenty-seven articles involving 39 independent groups fulfilled the predefined criteria. Overall, no significance was observed for all examined polymorphisms under allelic and dominant models. When restricting groups to CAD patients with diabetes mellitus or renal disease, deviations of risk estimates from the unity were stronger than overall estimates for all polymorphisms except for G1704A due to limited available studies. For example, under dominant model, having -429C allele increased the odds of developing CAD in diabetic patients by 1.22-fold (95% confidence interval (95% CI) 0.99-1.51; P = 0.06; I (2) = 6.7%) compared with that of overall estimate of 1.15-fold (95% CI: 0.97-1.36; P = 0.111; I (2) = 18.0%). Circulating sRAGE levels were non-significantly lower in CAD patients than in controls, whereas this reduction was totally and significantly reversed in CAD patients with diabetes mellitus (weighted mean difference: 185.71 pg/ml; 95% CI: 106.82 to 264.61 pg/ml). Circulating esRAGE levels were remarkably lower in CAD patients, as well as in subgroups with or without diabetes mellitus and without renal disease.

Conclusions: Our findings demonstrated that association of AGER genetic polymorphisms with CAD was potentiated in patients with diabetes mellitus or renal disease. Practically, circulating esRAGE might be a powerful negative predictor for the development of CAD.

Show MeSH

Related in: MedlinePlus

Overall estimates of AGER gene four polymorphisms examined for CAD under allelic model.The summary odds ratio (OR) is shown by the middle of a solid diamond whose left and right extremes represent the corresponding 95% confidence interval (95% CI). Horizontal axis represents ORs, which were calculated against controls for each study.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3722145&req=5

pone-0070834-g002: Overall estimates of AGER gene four polymorphisms examined for CAD under allelic model.The summary odds ratio (OR) is shown by the middle of a solid diamond whose left and right extremes represent the corresponding 95% confidence interval (95% CI). Horizontal axis represents ORs, which were calculated against controls for each study.

Mentions: The fact that only three groups were available for G1704A precluded further subgroup analyses. Pooling all qualified groups detected no statistical significance for AGER gene four polymorphisms in association with CAD under allelic and dominant models (Figure 2 and Tables 3–5). Further restricting groups to CAD patients with diabetes mellitus found that deviations of risk estimates from the unity were stronger than the overall estimates, except for Gly82Ser under allelic model. For example, under dominant model, having -429C allele increased the odds of developing CAD in diabetic patients by 1.22-fold (95% CI: 0.99–1.51) compared with that of overall estimate of 1.15-fold (95% CI: 0.97–1.36). Contrastingly, the risk magnitude was alleviated for T-429C, T-374A, and Gly82Ser in CAD patients without diabetes mellitus. Moreover, in CAD patients without renal disease, deviations of risk estimates from the unity was enhanced, albeit non-significant, than the overall estimates, especially for Gly82Ser (allelic model: OR = 1.26; 95% CI: 0.92–1.74 and dominant model: OR = 1.28; 95% CI: 0.83–1.96). Significant heterogeneity was observed for T-374A (allelic model only) and Gly82Ser. There was high probability of publication bias for T-374A and Gly82Ser in CAD patients without diabetes mellitus. Further evidence of selective publication indicated that there were respectively three, two, and two missing groups required to make the funnel plot symmetrical for T-429C, T-374A and G1704A (Figure 3).


Association of four genetic polymorphisms of AGER and its circulating forms with coronary artery disease: a meta-analysis.

Peng F, Hu D, Jia N, Li X, Li Y, Chu S, Zhu D, Shen W, Lin J, Niu W - PLoS ONE (2013)

Overall estimates of AGER gene four polymorphisms examined for CAD under allelic model.The summary odds ratio (OR) is shown by the middle of a solid diamond whose left and right extremes represent the corresponding 95% confidence interval (95% CI). Horizontal axis represents ORs, which were calculated against controls for each study.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3722145&req=5

pone-0070834-g002: Overall estimates of AGER gene four polymorphisms examined for CAD under allelic model.The summary odds ratio (OR) is shown by the middle of a solid diamond whose left and right extremes represent the corresponding 95% confidence interval (95% CI). Horizontal axis represents ORs, which were calculated against controls for each study.
Mentions: The fact that only three groups were available for G1704A precluded further subgroup analyses. Pooling all qualified groups detected no statistical significance for AGER gene four polymorphisms in association with CAD under allelic and dominant models (Figure 2 and Tables 3–5). Further restricting groups to CAD patients with diabetes mellitus found that deviations of risk estimates from the unity were stronger than the overall estimates, except for Gly82Ser under allelic model. For example, under dominant model, having -429C allele increased the odds of developing CAD in diabetic patients by 1.22-fold (95% CI: 0.99–1.51) compared with that of overall estimate of 1.15-fold (95% CI: 0.97–1.36). Contrastingly, the risk magnitude was alleviated for T-429C, T-374A, and Gly82Ser in CAD patients without diabetes mellitus. Moreover, in CAD patients without renal disease, deviations of risk estimates from the unity was enhanced, albeit non-significant, than the overall estimates, especially for Gly82Ser (allelic model: OR = 1.26; 95% CI: 0.92–1.74 and dominant model: OR = 1.28; 95% CI: 0.83–1.96). Significant heterogeneity was observed for T-374A (allelic model only) and Gly82Ser. There was high probability of publication bias for T-374A and Gly82Ser in CAD patients without diabetes mellitus. Further evidence of selective publication indicated that there were respectively three, two, and two missing groups required to make the funnel plot symmetrical for T-429C, T-374A and G1704A (Figure 3).

Bottom Line: For example, under dominant model, having -429C allele increased the odds of developing CAD in diabetic patients by 1.22-fold (95% confidence interval (95% CI) 0.99-1.51; P = 0.06; I (2) = 6.7%) compared with that of overall estimate of 1.15-fold (95% CI: 0.97-1.36; P = 0.111; I (2) = 18.0%).Circulating sRAGE levels were non-significantly lower in CAD patients than in controls, whereas this reduction was totally and significantly reversed in CAD patients with diabetes mellitus (weighted mean difference: 185.71 pg/ml; 95% CI: 106.82 to 264.61 pg/ml).Practically, circulating esRAGE might be a powerful negative predictor for the development of CAD.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

ABSTRACT

Background: Considerable efforts have been devoted to evaluating the association of the receptor for advanced glycation end-products (gene AGER and protein: RAGE) genetic variants to coronary artery disease (CAD); the results, however, are often irreproducible. To generate more information, we sought to explore four common polymorphisms of AGER and its circulating forms associated with the risk of CAD via a meta-analysis.

Methodology/principal findings: Articles were identified by searching PubMed, EMBASE, Wanfang and CNKI databases before March 2013. Qualified articles had case-control designs and investigated AGER four polymorphisms (T-429C, T-374A, Gly82Ser, G1704A) or circulating soluble RAGE (sRAGE) or endogenous secretory RAGE (esRAGE) levels associated with CAD. Twenty-seven articles involving 39 independent groups fulfilled the predefined criteria. Overall, no significance was observed for all examined polymorphisms under allelic and dominant models. When restricting groups to CAD patients with diabetes mellitus or renal disease, deviations of risk estimates from the unity were stronger than overall estimates for all polymorphisms except for G1704A due to limited available studies. For example, under dominant model, having -429C allele increased the odds of developing CAD in diabetic patients by 1.22-fold (95% confidence interval (95% CI) 0.99-1.51; P = 0.06; I (2) = 6.7%) compared with that of overall estimate of 1.15-fold (95% CI: 0.97-1.36; P = 0.111; I (2) = 18.0%). Circulating sRAGE levels were non-significantly lower in CAD patients than in controls, whereas this reduction was totally and significantly reversed in CAD patients with diabetes mellitus (weighted mean difference: 185.71 pg/ml; 95% CI: 106.82 to 264.61 pg/ml). Circulating esRAGE levels were remarkably lower in CAD patients, as well as in subgroups with or without diabetes mellitus and without renal disease.

Conclusions: Our findings demonstrated that association of AGER genetic polymorphisms with CAD was potentiated in patients with diabetes mellitus or renal disease. Practically, circulating esRAGE might be a powerful negative predictor for the development of CAD.

Show MeSH
Related in: MedlinePlus