Lipoprotein(a), polymorphisms in the LPA gene, and incident venous thromboembolism among 21 483 women

Danik, Jacqueline Suk; Buring, Julie E.; Chasman, Daniel I.; Zee, Robert Y.L.; Ridker, Paul M.; Glynn, Robert J.

doi:10.1111/jth.12056

Cited by 35 publications

(19 citation statements)

References 16 publications

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“…12,16,17 Lp(a) has been implicated in both atherogenesis and thrombosis. [18][19][20][21][22][23][24][25] Our study also demonstrated that the plasma Lp(a) levels were significantly elevated according to the quartiles of the Gensini scores in CAD patients. The alleles of 2 SNPs in the LPA gene, rs10455872 and rs3798220, have been shown to be associated with high plasma levels of Lp(a) and CAD in Europeans.…”

Section: Discussionsupporting

confidence: 71%

Functional Variant in the SLC22A3-LPAL2-LPA Gene Cluster Contributes to the Severity of Coronary Artery Disease

Wang¹,

Chen²,

Zeng³

et al. 2016

ATVB

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Objective— Recent genome-wide association studies have identified that genetic variants in the SLC22A3-LPAL2-LPA gene cluster influence plasma lipoprotein(a) [Lp(a)] concentration. However, the association between this gene cluster and the severity of coronary artery disease (CAD), especially the potential underlying mechanism, remains unclear. The purpose of this study was to investigate the association between variation in the SLC22A3-LPAL2-LPA gene cluster and CAD. Approach and Results— We performed 2-stage case–control studies in a Chinese Han population. The variant genotypes were examined for their association with both Lp(a) level and severity of CAD. Putative mechanisms were also evaluated. One single nucleotide polymorphism, rs3088442, in the SLC22A3-LPAL2-LPA gene cluster was significantly associated with both plasma Lp(a) levels and CAD severity. The gene dosage of the risk allele at rs3088442 indicated a robust association with left main trunk disease ( P =0.046), number of vascular lesions ( P =4.5×10 –3 ), and Gensini scores ( P =0.012) in patients with CAD. Reporter gene analysis indicated that the rs3088442 G allele might suppress miR-147a binding to the 3′ untranslated region of SLC22A3 , resulting in altered SLC22A3 and LPA gene expression ( P =0.015 and 9.2×10 –6 , respectively), possibly explaining the increased plasma Lp(a) levels and risk of CAD. Conclusions— The genotype of rs3088442 within the SLC22A3-LPAL2-LPA gene cluster may contribute to regulation of plasma Lp(a) levels and possibly to the severity of CAD in a Chinese Han population.

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Section: Discussionsupporting

confidence: 71%

Functional Variant in the SLC22A3-LPAL2-LPA Gene Cluster Contributes to the Severity of Coronary Artery Disease

Wang¹,

Chen²,

Zeng³

et al. 2016

ATVB

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“…When applied to assessment of associations between genetically elevated Lp(a) levels and different forms of venous thrombosis, however, the results have been uniformly negative (129)(130)(131). These findings quite definitely rule out a role for elevated Lp(a) in the etiology of venous thrombosis.…”

Section: Arterial Thrombosismentioning

confidence: 93%

“…More recently, however, genetic approaches have provided strong evidence against a role for Lp(a) in venous thrombosis (129)(130)(131). Because certain SNPs, such as rs3798220 (Ile4399→Met) and rs10455872 (intronic A/G polymorphism), are strongly associated with plasma Lp(a) concentrations, they can serve as surrogate markers for Lp(a) concentrations while also facilitating measurement in very large prospective cohorts where measurement of Lp(a) concentrations would be either cost-prohibitive or otherwise impossible.…”

Section: Venous Thrombosis and Thromboembolismmentioning

confidence: 99%

Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease?

Boffa

Koschinsky

2016

Journal of Lipid Research

205

125

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“…Although there have been discrepant results reported in the past, 3 recent, large, studies each also assessing LPA genotype at SNPs strongly associated with Lp(a) levels have concluded that no relationship between elevated Lp(a) and venous thromboembolism exists. [47][48][49] One study argued that this is evidence against a role for Lp(a) in the thrombotic complications of atherosclerosis. 47 There are, however, notable differences between the thrombi in arterial and venous compartments, with arterial thrombi being more platelet-rich, fibrin-poor, and initiated by the thrombogenic contents of the atherosclerotic core.…”

Section: Lipoprotein(a)mentioning

confidence: 99%