Lipoprotein(a) and the significance of the association between platelet glycoprotein IIIa polymorphisms and the risk of premature myocardial infarction

Joven, Jorge; Simó, José M; Vilella, Elisabet; Camps, Jordi; Febrer, Gabriel de; Camprubí, Mercedes; Richart, C; Bardajı́, Alfredo; Casao, E.; Pocovı́, Miguel; Civeira, Fernando

doi:10.1016/s0021-9150(98)00076-8

Cited by 35 publications

(20 citation statements)

References 35 publications

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“…The association between PlA2 carriage and MI in male subjects was observed to be consistent with the primary analysis ( n = 8,686; OR 1.145, 95% CI 1.018–1.288; p = 0.024) [72], [84]–[86], [97], [99], [114], [115], [120], [123], [127]. Only two studies provided data for female subjects, resulting in no significant association observed in these ( n = 5,237; OR 0.961, 95% CI 0.703–1.312; p = 0.801) [86], [120].…”

Section: Resultssupporting

confidence: 80%

“…These data are all displayed in Table 3. Subgroup analysis of crude data using only healthy controls found an increased association between PlA2 carriage and MI compared to the primary analysis ( n = 29,907; OR 1.098, 95% CI 1.033–1.166; p = 0.003) [71]–[73], [81]–[84], [86]–[91], [96], [98], [99], [102]–[104], [107], [108], [110]–[113], [115]–[117], [119]–[125], [127], [128], whereas analysis of raw data using controls with known coronary artery disease found no significant association ( n = 11,819; 95% CI 0.941–1.114; p = 0.583) (Figure 5) [80], [85], [87], [88], [92]–[94], [96], [100], [105], [106], [108], [114], [118], [126]–[128].…”

Section: Resultsmentioning

confidence: 82%

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The PlA1/A2 Polymorphism of Glycoprotein IIIa as a Risk Factor for Myocardial Infarction: A Meta-Analysis

2014

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BackgroundThe PlA2 polymorphism of glycoprotein IIIa (GPIIIa) has been previously identified as being associated with myocardial infarction (MI), but whether this represents a true association is entirely unclear due to differences in findings from different studies. We performed a meta-analysis to evaluate whether this polymorphism is a risk factor for MI.MethodsElectronic databases (MEDLINE and EMBASE) were searched for all articles evaluating genetic polymorphisms of GPIIIa. For studies where acute coronary events were recorded in association with genetic analysis, pooled odds ratios (ORs) were calculated using fixed-effects and random-effects models. The primary outcome measure was MI, and a secondary analysis was also performed for acute coronary syndromes (ACS) more generally.Findings57 studies were eligible for statistical analysis and included 17,911 cases and 24,584 controls. Carriage of the PlA2 allele was significantly associated with MI (n = 40,692; OR 1.077, 95% CI 1.024–1.132; p = 0.004) but with significant publication bias (p = 0.040). The degree of association with MI increased with decreasing age of subjects (≤45 years old: n = 9,547; OR 1.205, 95% CI 1.067–1.360; p = 0.003) and with adjustment of data for conventional cardiovascular risk factors (n = 12,001; OR 1.240, 95% CI 1.117–1.376; p<0.001). There was a low probability of publication bias for these subgroup analyses (all p<0.05).ConclusionsThe presence of significant publication bias makes it unclear whether the association between carriage of the PlA2 allele and MI is true for the total population studied. However for younger subjects, the relative absence of conventional cardiovascular risk factors results in a significant association between carriage of the PlA2 allele and MI.

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Section: Resultssupporting

confidence: 80%

Section: Resultsmentioning

confidence: 82%

The PlA1/A2 Polymorphism of Glycoprotein IIIa as a Risk Factor for Myocardial Infarction: A Meta-Analysis

2014

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“…It is also notable that ITGB3 Leu33Pro, which has been previously associated with CVD phenotypes (Carter et al 1997Joven et al 1998Mikkelsson et al 2000Mikkelsson et al , 2001Pastinen et al 1998;Wagner et al 1998;Weiss et al 1996), was not among the strongest associations for serotonin or Lp(a) levels, by either method. This suggests that the Pl A2 allele may be a marker for an associated haplotype (or an allele on that haplotype), but is unlikely to be the sole causative SNP for the association with serotonin level in the Hutterites.…”

Section: Discussionmentioning

confidence: 81%

“…In addition to being associated with high serotonin level in our study (Weiss et al 2004b), the protein encoded by the Pl A2 allele has been associated with markers of platelet activation, such as increased and more stable interactions with fibrinogen (Feng et al 1999;Goodall et al 1999;Sajid et al 2002;Undas et al 2001;Vijayan et al 2000), enhanced ability of platelets to aggregate and generate thrombin (Carter et al1997(Carter et al , 1998Joven et al 1998;Mikkelsson et al 2000Mikkelsson et al , 2001Pastinen et al 1998;Wagner et al 1998;Weiss et al 1996), and enhanced cell migration (Sajid et al 2002). Further, the Pl A2 allele has been associated with cardiovascular phenotypes such as coronary thrombosis and atherosclerosis (Mikkelsson et al 2000(Mikkelsson et al , 2001Weiss et al 1996), stroke (Carter et al 1998;Wagner et al 1998), myocardial infarction (Carter et al 1997;Pastinen et al 1998) and high plasma lipoprotein(a) [Lp(a)] concentration (Joven et al 1998), although these associations were not present in all samples studied [for a negative study of Lp(a), see Batalla et al 1999, and for other examples of negative studies, see the meta-analysis by Zhu et al 2000]. …”

Section: Introductionmentioning

confidence: 69%

Variation in ITGB3 has sex-specific associations with plasma lipoprotein(a) and whole blood serotonin levels in a population-based sample

Weiss

Abney

Parry³

et al. 2005

Hum Genet

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A recent genome-scan identified the Leu33Pro polymorphism in the beta3 integrin (ITGB3) gene as a quantitative trait locus for whole blood serotonin level in a large Hutterite pedigree. Because both the Leu33Pro polymorphism and the serotonin system have been implicated in cardiovascular disease (CVD) risk and treatment response, we studied additional variation in ITGB3 and its relationship to intermediate phenotypes associated with CVD in the same population. We examined associations between 15 single nucleotide polymorphisms (SNPs) across ITGB3 and five CVD-related traits in the Hutterites: plasma levels of high density lipoprotein-cholesterol (HDL-c), triglycerides (TG), low density lipoprotein-cholesterol (LDL-c), and lipoprotein(a) [Lp(a)] and blood pressure or hypertension. Seven of these SNPs in ITGB3 were associated with whole blood serotonin. Among the intermediate CVD-related phenotypes, only Lp(a) was associated with multiple ITGB3 SNPs, five of which were also associated with serotonin. A sex-stratified analysis revealed that the association between ITGB3 and Lp(a) is present only in females, whereas the association between ITGB3 and serotonin is concentrated in males. Our results suggest that variation in ITGB3 in addition to Leu33Pro could contribute to susceptibility to CVD and serotonin in a sex-specific manner.

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“…In spite of conflicting and inconsistent evidence whether Lp(a) may be pro-aggregatory per se, some reports suggest novel alternative mechanisms by which Lp(a) might contribute to atherothrombosis [23]. Some epidemiological surveys point that clustering of this lipoprotein with several other recognised risk factors, including fibrinogen, homocysteine, platelet glycoprotein polymorphisms or other lipoproteins, increases the risk of vascular events [35].…”

Section: Other Plasma Lipoproteinsmentioning

confidence: 99%

Blood Platelet Reactivity and its Pharmacological Modulation in (People with) Diabetes Mellitus

Watała

2005

CPD

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Blood platelets play a crucial role in physiological haemostasis and in pathology of prothrombotic states, including atherosclerosis. In this paper, we review major factors underlying altered platelet reactivity, with special attention paid to abnormalities in platelet function in people with diabetes mellitus (DM). The overall picture of platelet abnormalities in DM, including altered adhesion and aggregation, is hypersensitivity of diabetic platelets to agonists. "Primed" diabetic platelets respond more frequently even to subthreshold stimuli, sooner become exhausted, consumed and finally hyposensitive, thus contributing to accelerated thrombopoiesis and release of 'fresh' hyperreactive platelets. In diabetes disturbed carbohydrate and lipid metabolism may lead to physicochemical changes in cell membrane dynamics, and consequently result in altered exposure of surface membrane receptors. These phenomena, together with increased fibrinogen binding, prostanoid metabolism, phosphoinositide turnover and calcium mobilisation often present in diabetic patients, contribute to enhanced risk of small vessel occlusions and accelerated development of atherothrombotic disease of coronary, cerebral and other vessels in diabetes. As platelet hypersensitivity in DM makes a major contribution to enhanced risk of thromboembolic macroangiopathy, and consequently enhanced morbidity and mortality, it validates use of antiplatelet agents in diabetic individuals. Platelet hyperreactivity may be cured with various antiplatelet drugs to a considerably large extent notwithstanding, evidence gathered from clinical and experimental surveys shows that this approach may not always be equally efficient in people with diabetes. Observations from clinical studies rather support the use of multifactorial strategy under such circumstances, like a combined therapy of aspirin plus either purinoreceptor blocker or GPIIb-IIIa antagonist.

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Lipoprotein(a) and the significance of the association between platelet glycoprotein IIIa polymorphisms and the risk of premature myocardial infarction

Cited by 35 publications

References 35 publications

The PlA1/A2 Polymorphism of Glycoprotein IIIa as a Risk Factor for Myocardial Infarction: A Meta-Analysis

The PlA1/A2 Polymorphism of Glycoprotein IIIa as a Risk Factor for Myocardial Infarction: A Meta-Analysis

Variation in ITGB3 has sex-specific associations with plasma lipoprotein(a) and whole blood serotonin levels in a population-based sample

Blood Platelet Reactivity and its Pharmacological Modulation in (People with) Diabetes Mellitus

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