Three SNPs on chromosome 9p21 confer increased risk of myocardial infarction in Chinese subjects

Zhang, Qi; Cheng, Shuang-shuang; Wan, Xinhong; Cao, Feifei; Li, Lei; Chen, Xing-dong; Liu, Wenjuan; Yang, Xinchun; Li, Jin

doi:10.1016/j.atherosclerosis.2009.04.017

Cited by 24 publications

(20 citation statements)

References 14 publications

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“…NS differences were obtained in allele and genotype frequencies between cases and controls; however, there was a clear trend in the three SNPs of an increased frequency of the G allele (AG+GG genotypes) in patients with AT compared to controls. OR values obtained suggest that these SNPs, considered independently, do not confer a higher risk of AT, in contrast to what is published in previous studies [11,12].…”

Section: Resultscontrasting

confidence: 56%

“…It has been reported a strong association between the polymorphisms rs10757274, rs2383206 and rs10757278 and the onset of cardiovascular disease in African American and Hispanic individuals from USA, in Europeans and Asians [1,11,12,18,[20][21][22]. However, little has been studied in Latin American individuals who have high genetic and cultural variability.…”

Section: Discussionmentioning

confidence: 99%

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rs10757278 (9p21 region) affects the risk of arterial thrombosis in male individuals from the state of anzoátegui, Venezuela

Jimenez¹,

Lugo²,

Guerra³

2013

J Genet Stud

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Background: Numerous single nucleotide polymorphisms (SNPs) located in chromosomal region 9p21 have been associated with cardiovascular disease, most of these studies in European populations. We have no knowledge of studies conducted in admixed populations populations as the Latin Americans. For this reason we decided to study the association of SNPs rs2383206, rs10757274 and rs10757278, together with some non-genetic factors with arterial thrombotic events (AT), in individuals from the north-eastern portion of Venezuela. Methods: Gender, age and non-genetic risk variables were evaluated in 119 patients with AT and 119 control subjects. Genotypes were identified using TaqMan probes. The odds ratio (OR) for genotypes alone and in conjunction with non-genetic variables were estimated. Results: There was a consistent association of rs10757278 with AT, increased in males (OR=2.38). The medium-low socioeconomic status also confers a significant risk for AT in both sexes (OR=4.04). Haplotypes with at least two A alleles, proved to be protective (OR=0.53) in developing arterial thrombosis. Conclusions: There was a consistent association with AT for the rs10757278 polymorphism, increased in males. Sex and socioeconomic status were also significant risk factors in this study reinforcing the importance in studying other variables such as environmental and sex differences together with the genetic structure of each population when analyzing risks for AT diseases. These results serve as a guide when searching for markers of risk for this disease common in Venezuela.

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Section: Resultscontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

rs10757278 (9p21 region) affects the risk of arterial thrombosis in male individuals from the state of anzoátegui, Venezuela

Jimenez¹,

Lugo²,

Guerra³

2013

J Genet Stud

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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%

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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“…The association between the five highly correlated SNPs in the 9p21 region and CHD or its components has since been replicated in over 22 articles, which include 47 datasets, summarized in a recent review and meta-analysis [4•]. The studies have been largely in Caucasian populations, but the association has been seen in Asian populations as well, specifically Han Chinese [5][6][7], Japanese [8,9], and Korean [8,10], and also in Hispanics [11]. The overall effect on CHD was estimated as a relative risk increase of 1.25 with each risk allele [4•].…”

Section: Evidence Of Association Between Variation At 9p21 and Cvdmentioning

confidence: 97%

Does the 9p21 Genetic Variant Have a Role in Cardiovascular Risk Prediction?

Paynter

2010

Curr Cardiovasc Risk Rep

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Genetic variation at 9p21 has been one of the strongest, most common, and most consistent genetic markers associated with cardiovascular disease. Associations with 9p21 have been replicated across multiple populations and cardiovascular disease outcomes and have even been shown with subclinical markers of atherosclerosis. 9p21 variation is also not associated with traditional cardiovascular risk factors, and thus is a natural candidate to evaluate for potential improvement in cardiovascular risk prediction. However, 9p21 variation has only shown modest, if any, improvement in assessment and prediction of cardiovascular risk. Although genetic information has led to useful biologic knowledge, it does not yet appear to be ready for incorporation into clinical cardiovascular disease risk prediction tools, nor can widespread population screening be recommended at this time.

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Three SNPs on chromosome 9p21 confer increased risk of myocardial infarction in Chinese subjects

Cited by 24 publications

References 14 publications

rs10757278 (9p21 region) affects the risk of arterial thrombosis in male individuals from the state of anzoátegui, Venezuela

rs10757278 (9p21 region) affects the risk of arterial thrombosis in male individuals from the state of anzoátegui, Venezuela

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

Does the 9p21 Genetic Variant Have a Role in Cardiovascular Risk Prediction?

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