Gene Variants of VAMP8 and HNRPUL1 Are Associated With Early-Onset Myocardial Infarction

Shiffman, Dov; Rowland, Charles M.; Louie, Judy Z.; Luke, May M.; Bare, Lance A.; Bolonick, Joel I.; Young, Bradford A.; Catanese, Joseph J.; Stiggins, Charles F.; Pullinger, Clive R.; Topol, Eric J.; Malloy, Mary J.; Kane, John P.; Ellis, Stephen G.; Devlin, James J.

doi:10.1161/01.atv.0000226543.77214.e4

Cited by 69 publications

(52 citation statements)

References 23 publications

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“…be associated with CHD in other studies: the ARIC risk allele of rs1010 in VAMP8 was associated with MI in three case-control studies 17 and the ARIC risk allele of rs20455 in KIF6 was associated with CHD in the placebo arms of two statin treatment studies. 18 For the other three SNPs (rs3900940 in MYH15, rs7439293 in PALLD, and rs2298566 in SNX19), the same risk allele was also associated with MI (P Ͻ 0.1) in the two casecontrol studies reported here (Table 8, supporting information, available online only) and with CHD in ARIC.…”

Section: Five Gene Variants Identify Risk Of Chd In Aricmentioning

confidence: 88%

“…In estimating ranges of prior probability, we divided five SNPs into two groups. For the group of SNPs whose prior association with CHD had been described in published studies that adjusted for multiple hypothesis testing, we assumed a higher prior probability: False discovery rate analysis was used to account for multiple testing for the SNP in VAMP8, 17 and the Bonferroni method was used for the SNP in KIF6. 18 We assumed a lower prior probability of association for the SNPs in MYH15, PALLD, and SNX19; these were nominally associated with CHD in the two case-control studies of MI described in this report (Table 8, supporting information, available online only).…”

Section: Discussionmentioning

confidence: 99%

“…The SNP in VAMP8 was associated with early-onset MI in three case-control studies, with a false discovery rate of Ͻ0.1 in the third study. 17 Because the false discovery rate was Ͻ0.1, we used prior probabilities that ranged from 0.9 to 0.09. The KIF6 SNP (rs20455) was associated with CHD in the placebo arms of two CHD prevention trials and the association remained significant after a Bonferroni correction for multiple testing.…”

Section: Statistical Analysesmentioning

confidence: 99%

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Five common gene variants identify elevated genetic risk for coronary heart disease

Bare¹,

Morrison

Rowland³

et al. 2007

Genetics in Medicine

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Purpose: Because multiple genetic variants influence risk for coronary heart disease, we combined multiple variants that had been associated with coronary heart disease in several studies into a genetic risk score and asked whether a high genetic risk score would be significantly associated with coronary heart disease after accounting for traditional risk factors. Methods: We considered five variants that were associated with coronary heart disease in two studies and confirmed in the Atherosclerosis Risk in Communities study: rs20455 (KIF6), rs3900940 (MYH15), rs7439293 (PALLD), rs2298566 (SNX19), and rs1010 (VAMP8). We calculated a genetic risk score for each Atherosclerosis Risk in Communities study participant and estimated the hazard ratio for incident coronary heart disease of a high genetic risk score (compared with not-high) in Cox models that adjusted for traditional risk factors during a median of 13 years of follow-up. Results: For white participants with a high genetic risk score (4% of the 9129 whites), compared with those without a high genetic risk score, the hazard ratio for incident coronary heart disease was 1.57 (95% confidence interval 1.21-2.04; P ϭ 0.001). Internal validation using bootstrap samples estimated that a hazard ratio of 1.43 could be expected in external populations. Conclusions:After adjusting for traditional risk factors, those with a high genetic risk score had a 57% increased risk of incident coronary heart disease in the Atherosclerosis Risk in Communities study. Genet Med 2007:9(10):682-689.

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Section: Five Gene Variants Identify Risk Of Chd In Aricmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

See 1 more Smart Citation

Five common gene variants identify elevated genetic risk for coronary heart disease

Bare¹,

Morrison

Rowland³

et al. 2007

Genetics in Medicine

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“…rs10757278G was independently associated with an increased risk for the incidence of CAD. Shiffman et al (2006) in a study of white Americans observed that the rs1010 locus in VAMP8, a gene involved in platelet degranulation (OR = 1.75; 90%CI = 1.17-2.62; P = 0.025), and the rs11881940 site in HNRPUL1, a gene encoding ribonuclease (OR = 1.92; 90%CI = 1.28-2.86; P = 0.0043), were associated with early-onset MI (Gabler et al, 1998;Polgar et al, 2002). However, we found that the rs1010 locus was not significantly correlated with CAD, a result inconsistent with those reported by Duan et al (2010), and this inconsistency may be due to differences in individual susceptibility to CAD.…”

Section: Discussionmentioning

confidence: 99%

Gene polymorphisms associated with susceptibility to coronary artery disease in Han Chinese people

et al. 2014

Genet. Mol. Res.

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ABSTRACT. This study investigated 5 single nucleotide polymorphism (SNP) haplotypes in susceptibility genes for coronary artery disease (CAD) and the putative involvement of these SNPs in CAD in the Chinese Han population. From March 2008 to June 2009, we selected 119 CAD patients and 115 subjects not related to the CAD of Chinese Han origin as controls. The SNP genotypes were performed by multiplex SNaPshot technology. The HNRPUL1 gene rs11881940T and GATA2 gene rs3803T loci were highly correlated with CAD (P < 0.05). rs10757278G increased the risk of CAD in patients indicated by an odds ratio (OR) = 1.242 [95% confidence interval (CI) = 1.04-1.49]; rs11881940T and rs3803T were protective factors for CAD with ORs = 0.767 (95%CI = 0.61-0.97) and 0.53 (95%CI = 0.40-0.72), respectively. Analysis of the rs10757278, rs11881940 and rs3803 loci showed that haplotypes ATC (OR = 4.26; 95%CI = 2.85-6.40, P < 0.01), GAC (OR = 1.50; 95%CI = 1.25-1.81, P < 0.01) and GAT (OR = 1.53; 95%CI = 1.12-2.09, P < 0.01) were CAD risk factors, whereas GTC was protective (OR = 0.48; 95%CI = 0.32-0.72, P < 0.01). ATC and glucose were positively correlated (OR = 1.91; 95%CI = 1.01-3.61, P < 0.05). GAT was a risk factor for hypertension (OR = 2.86; 95%CI = 1.40-5.83, P < 0.01). In conclusion, polymorphisms and haplotype analysis of susceptibility genes for CAD can improve predicting this disease and will enable early diagnosis of CAD.

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“…22 Genotyping accuracy of the multiplex methodology and kPCR has been assessed in three previous studies by comparing genotype calls from multiplex OLA assays with those from real time kPCR assays for the same SNPs, and the overall concordance of the genotype calls from these two methods was >99% in each of these studies. [23][24][25] Primer sequences are available upon request.…”

Section: F9 Malmö and Endogenous Thrombin Potentialmentioning

confidence: 99%

F9 Malmo, factor IX and deep vein thrombosis

Bezemer¹,

Arellano²,

Tong³

et al. 2009

Haematologica

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BackgroundWe recently reported the association between the Malmö sequence variant in F9 (rs6048) and deep vein thrombosis. Design and MethodsWe aimed to study whether the association between F9 Malmö and deep vein thrombosis is explained by linkage disequilibrium with nearby single-nucleotide polymorphisms, and whether the association is explained biologically by F9 Malmö affecting factor IX antigen levels or activation of factor IX. We investigated the association of F9 Malmö and 28 nearby single-nucleotide polymorphisms with deep vein thrombosis in men from two case-control studies, LETS (n=380) and MEGA (n=1,469). We assessed the association of F9 Malmö with factor IX antigen level in male control subjects from LETS (n=191) and two subsets of MEGA (n=823 and n=484) and the association with endogenous thrombin potential in LETS control men. We studied the association between F9 Malmö and factor IX activation peptide in 1,199 healthy middle-aged men from the NPHS-II cohort. ResultsIn the combined LETS and MEGA studies, the odds ratio (95% confidence interval) for the G allele of F9 Malmö, compared with the A allele, was 0.80 (0.69-0.93). One singlenucleotide polymorphism in F9, rs422187, was strongly linked to F9 Malmö (r 2 =0.94) and was similarly associated with deep vein thrombosis. No other single-nucleotide polymorphism or haplotype tested was more strongly associated. Factor IX antigen level, factor IX activation peptide levels and endogenous thrombin potential did not differ between F9 Malmö genotypes. ConclusionsThe F9 Malmö sequence variant was the most strongly associated with deep vein thrombosis among common single-nucleotide polymorphisms in the region. However, the biological mechanism by which F9 Malmö affects risk remains unknown.Key words: factor IX, single nucleotide polymorphism, venous thrombosis.Citation: Bezemer ID, Arellano AR, Tong C, Rowland CM, Ireland HA, Bauer KA, Catanese J, Reitsma PH, Doggen CJM, Devlin JJ, Rosendaal FR, and Bare LA. F9 Malmö, factor IX and deep vein thrombosis. Haematologica 2009; 94:693-699. doi:10.3324/haematol.2008

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Gene Variants of VAMP8 and HNRPUL1 Are Associated With Early-Onset Myocardial Infarction

Abstract: Variants in 2 genes were associated with early-onset MI: VAMP8, which is involved in platelet degranulation, and HNRPUL1, which encodes a ribonuclear protein. The identification of these variants could improve understanding of disease mechanisms and suggest novel drug targets.

Cited by 69 publications

References 23 publications

Five common gene variants identify elevated genetic risk for coronary heart disease

Five common gene variants identify elevated genetic risk for coronary heart disease

Gene polymorphisms associated with susceptibility to coronary artery disease in Han Chinese people

F9 Malmo, factor IX and deep vein thrombosis

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