Four SNPS on Chromosome 9p21 Confer Risk to Premature, Familial CAD and MI in an American Caucasian Population (GeneQuest)

Abdullah, Kalil G.; Li, L.; Shen, Gong-Qing; Hu, Yan; Yang, Yue; MacKinlay, K. G.; Topol, Eric J.; Wang, Q. K.

doi:10.1111/j.1469-1809.2008.00454.x

Cited by 69 publications

(56 citation statements)

References 11 publications

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“…In 2007, independent genome-wide association studies revealed nine highly correlated SNPs (r 2 > 0.8) in a new locus in the region of chromosome 9 (9p21.3), showing the greatest association with heterogeneous CAD of all of the loci analyzed so far (Helgadottir et al, 2007;McPherson et al, 2007;Samani et al, 2007). Since then, numerous studies have confirmed the association of this locus with CAD or myocardial infarction (MI) in populations of European origin (Abdullah et al, 2008;Anderson et al, 2008;Assimes et al, 2008;Lemmens et al, 2009;Koch et al, 2011) as well as Eastern (Shen et al, 2008a;Ding et al, 2009) and Southern Asia origin (AshokKumar et al, 2011). However, genetic heterogeneity was shown in Black subjects (Assimes et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

The rs10757278 Polymorphism of the 9p21.3 Locus Is Associated with Premature Coronary Artery Disease in Polish Patients

Niemiec

Górczyńska-Kosiorz²,

Iwanicki³

et al. 2012

Genetic Testing and Molecular Biomarkers

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Recently, genome-wide association studies have revealed a locus associated with coronary artery disease (CAD) and myocardial infarction, namely, 9p21.3. Its participation in the conditioning of the disease has been proven in many populations of European descent, but not yet in Slavs. Allelic variants of the rs10757278 polymorphism functionally affect the activity of the 9p21.3 locus; therefore, we conducted a study to determine whether the rs10757278 is associated with premature CAD in Polish patients. We studied 320 subjects aged 25-55 years, divided into two groups matched by sex and age: (1) patients with angiographically proven premature CAD (n = 160), and (2) blood donors as a control group (n = 160). The rs10757278 was genotyped using the method of fluorescently labeled allelespecific oligonucleotides. The frequency of the G allele was significantly higher in patients than in controls (58.2% vs. 42.8%, respectively, p = 0.011) and was similar to the frequency of the GG homozygotes (30.6% vs. 17.5%, respectively, p = 0.006). Both the GG homozygosity (odds ratio [OR] = 2.08, 95% confidence interval [CI]: 1.19-3.66) as well as the G allele (OR = 1.49, 95% CI: 1.08-2.07) have been associated with CAD in the analyzed population. These variants may be considered as risk factors, also in the Polish population.

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Section: Introductionmentioning

confidence: 99%

The rs10757278 Polymorphism of the 9p21.3 Locus Is Associated with Premature Coronary Artery Disease in Polish Patients

Niemiec

Górczyńska-Kosiorz²,

Iwanicki³

et al. 2012

Genetic Testing and Molecular Biomarkers

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“…Nineteen studies were based in Europe or the United States, [1][2][3][4][5][17][18][19][20][21][22][23][24][25][26][27][28][29][30] 6 in East Asia, [31][32][33][34][35][36] and 1 in North Africa. 37 Of these studies, 5 were prospective, 17 …”

Section: Meta-analysismentioning

confidence: 99%

“…Nineteen studies were based in Europe or the United States, 1-5,17-30 6 in East Asia, 31-36 and 1 in North Africa. 37 Of these studies, 5 were prospective, 17,21,25,28,30 2 were nested case-control, 22,29 and 19 were retrospective case-control studies. Five studies included only patients with MI, whereas 21 included patients with MI or coronary stenosis (defined by intervention procedures).…”

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confidence: 99%

Association of the 9p21.3 Locus With Risk of First-Ever Myocardial Infarction in Pakistanis

Saleheen¹,

Alexander²,

Rasheed³

et al. 2010

ATVB

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Objective-To examine variants at the 9p21 locus in a case-control study of acute myocardial infarction (MI) in Pakistanis and to perform an updated meta-analysis of published studies in people of European ancestry. Methods and Results-A total of 1851 patients with first-ever confirmed MI and 1903 controls were genotyped for 89 tagging single-nucleotide polymorphisms at locus 9p21, including the lead variant (rs1333049) identified by the Wellcome Trust Case Control Consortium. Minor allele frequencies and extent of linkage disequilibrium observed in Pakistanis were broadly similar to those seen in Europeans. In the Pakistani study, 6 variants were associated with MI (PϽ10 Ϫ2) in the initial sample set, and in an additional 741 cases and 674 controls in whom further genotyping was performed for these variants. For Pakistanis, the odds ratio for MI was 1.13 (95% CI, 1.05 to 1.22; Pϭ2ϫ10 Ϫ3) for each copy of the C allele at rs1333049. In comparison, a meta-analysis of studies in Europeans yielded an odds ratio of 1.31 (95% CI, 1.26 to 1.37) for the same variant (Pϭ1ϫ10 Key Words: myocardial infarction Ⅲ 9p21 Ⅲ Pakistanis Ⅲ risk factor Ⅲ South Asia Ⅲ meta-analysis V ariants at the 9p21.3 locus have been established as among the strongest common genetic factors associated with the risk of coronary artery disease (CAD) in people of European continental ancestry. [1][2][3][4][5] These variants are in highlinkage disequilibrium (LD) and span a 58-kb region that has multiple neighboring genes (CDKN2A, CDNK2B, and MTAP), without annotating to any single protein sequence. 5 An RNA coding gene, ANRIL, that overlaps with the risk To our knowledge, we report the first large-scale study of variants at the 9p21 locus in relation to risk of acute myocardial infarction (MI) in Pakistanis. This study involved 1851 patients with confirmed diagnoses of first-ever MI and 1903 control subjects from the Pakistan Risk of Myocardial Infarction Study 8 (PROMIS). Genotyping was conducted on 89 tagging single-nucleotide polymorphisms (SNPs) at the 9p21.3 locus, including the lead variant (rs1333049) identified by the Wellcome Trust Case Control Consortium in association with CAD. 1,2 To place our findings in context, we also report a literaturebased meta-analysis of relevant studies, encompassing information on 23 variants at the 9p21 locus in up to 38 250 CAD cases and 84 820 controls. The current meta-analysis substantially updates a previous relevant review, 5 involving data from an additional 82 117 participants and 20 additional variants. Methods Study DesignThis article follows the reporting recommendations of STrengthening the REporting of Genetic Association studies. 9 PROMIS is a casecontrol study of acute first-ever MI in urban Pakistan. 8 Patients with MI experienced the following: (1) symptoms within 24 hours of hospital presentation, (2) typical ECG characteristics (eg, Ն1-mm ST elevation in any Ն2 contiguous limb leads or new-onset left bundle branch block), and (3) a positive troponin test result (Ͼ1 ng/mL). Controls were indi...

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“…4 The finding has led to a plethora of further studies that have largely confirmed the association of the 9p21 locus with CAD and MI in both case-control and cohort studies and in multiple ethnic groups. [5][6][7][8][9][10][11][12] 9p21 represents the most replicated locus for CAD and MI to date. The risk allele as currently defined, until causal variants are identified, is common (allele frequency of almost 50%) and associated with a 20% to 30% increased risk per copy.…”

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confidence: 99%

Chromosome 9p21 and Cardiovascular Disease

Samani

Schunkert

2008

Circ Cardiovasc Genet

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Four SNPS on Chromosome 9p21 Confer Risk to Premature, Familial CAD and MI in an American Caucasian Population (GeneQuest)

Cited by 69 publications

References 11 publications

The rs10757278 Polymorphism of the 9p21.3 Locus Is Associated with Premature Coronary Artery Disease in Polish Patients

The rs10757278 Polymorphism of the 9p21.3 Locus Is Associated with Premature Coronary Artery Disease in Polish Patients

Association of the 9p21.3 Locus With Risk of First-Ever Myocardial Infarction in Pakistanis

Chromosome 9p21 and Cardiovascular Disease

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