Coronary Artery Disease–Associated Locus on Chromosome 9p21 and Early Markers of Atherosclerosis

Samani, Nilesh J.; Raitakari, Olli T.; Sipilä, Kalle; Tobin, Martin D.; Schunkert, Heribert; Juonala, Markus; Braund, Peter S.; Erdmann, Jeanette; Viikari, Jorma; Moilanen, Leena; Taittonen, Leena; Jula, Antti; Jokinen, Eero; Laitinen, Tomi; Hutri‐Kähönen, Nina; Nieminen, Markku S.; Kesäniemi, Y. Antero; Hall, Alistair S.; Hulkkonen, Janne; Kähönen, Mika; Lehtimäki, Terho

doi:10.1161/atvbaha.108.170332

Cited by 80 publications

(62 citation statements)

References 29 publications

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“…SNPs on chromosome 9p21 have been associated with carotid atherosclerotic lesions [11] but not with carotid IMT [11,[15][16][17][18], in contrast to our results. For the combined effects, a genetic score of SNPs associated with total cholesterol has been shown to be associated with carotid IMT [18,35].…”

Section: Main Findingscontrasting

confidence: 99%

“…These SNPs seem to influence vascular cell proliferation [8] and some studies have suggested that there are associations between the SNPs on chromosome 9p21 and coronary [9,10], carotid [11] and peripheral [12] atherosclerosis. However, other studies have shown either no or uncertain associations between these SNPs and the extent of coronary atherosclerosis [13,14] or early markers of carotid atherosclerosis [15][16][17][18][19]. Thus, whether or not there is an association between SNPs on chromosome 9p21 and generally increased atherosclerosis remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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A myocardial infarction genetic risk score is associated with markers of carotid atherosclerosis

Hamrefors

Hedblad

Engström

et al. 2011

Journal of Internal Medicine

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Abstract. Hamrefors V, Hedblad B, Engström G, Almgren P, Sjögren M, Melander O (Lund University, Malmö, Sweden). A myocardial infarction genetic risk score is associated with markers of carotid atherosclerosis. J Intern Med 2012;271: 271-281.Objective. To assess whether or not a genetic risk score that was previously shown to be associated with myocardial infarction (MI) and coronary artery disease (CAD) is also associated with markers of carotid atherosclerosis.Design. A total of 4022 middle-aged subjects from the general Swedish population were genotyped and individually assigned a genetic risk score based on 13 single-nucleotide polymorphisms (SNPs), previously associated with MI and CAD. The genetic score (Score-MI) was then related to carotid bulb intimamedia thickness (IMT), common carotid artery (CCA) IMT and to the occurrence of carotid plaques in the study population.Results. Score-MI was associated with IMT of the bulb (P < 0.001) and the CCA (P < 0.001) in unadjusted analyses, and with IMT of the bulb after adjustment for cardiovascular risk factors (P = 0.003). The effect size of Score-MI on IMT of the bulb was similar to that of LDL cholesterol. After adjustment for cardiovascular risk factors, Score-MI was also associated with the occurrence of carotid plaques (odds ratio per quintile of Score-MI = 1.11; 95% confidence interval 1.04-1.18; P = 0.001). In addition to SNPs with known effects on LDL levels, Score-MI showed nominal associations with increasing systolic blood pressure and decreasing C-reactive protein levels.Conclusions. This genetic risk score was independently associated with carotid bulb IMT and carotid plaques, providing evidence of an association with early markers of atherosclerosis. This might imply that the genetic MI risk conferred by the score is related to early atherosclerosis and that the risk score may identify at an early stage candidates at risk of developing intermediate phenotypes of atherosclerosis. Further studies should test whether or not assessing the genetic score could be valuable for early treatment decisions in these subjects.

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Section: Main Findingscontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A myocardial infarction genetic risk score is associated with markers of carotid atherosclerosis

Hamrefors

Hedblad

Engström

et al. 2011

Journal of Internal Medicine

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“…Several prospective studies have shown that chromosome 9p21 variation was associated with development of atherosclerosis and incident cardiovascular disease (14)(15)(16). However, Chen et al revealed that 9p21 conferred null effects on the severity or progression of coronary atherosclerosis in Caucasians (17).…”

Section: Discussionmentioning

confidence: 99%

Chromosome 9p21 polymorphism is associated with myocardial infarction but not with clinical outcome in Han Chinese

Peng¹,

Lü²,

Zhang³

et al. 2009

Clinical Chemistry and Laboratory Medicine

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Background: rs1333049 polymorphism on chromosome 9p21 has been shown to affect susceptibility to coronary artery disease (CAD) in Caucasians. This study examined the association of rs1333049 with myocardial infarction (MI), angiographic severity of CAD and clinical outcome after a first acute MI in Han Chinese. Methods: rs1333049 polymorphism was genotyped in 520 patients with a first acute MI and in 560 controls. The number of angiographically documented diseased coronary arteries (luminal diameter stenosis G50%), echocardiographic left ventricular ejection fraction (LVEF), and major adverse cardiac events (MACE) during follow-up (mean, 29"15 months) were recorded. Results: Patients with MI had higher frequencies of the CC genotype (30.0% vs. 20.7%) or C allele (55.5% vs. 46.2%) compared with controls (all p-0.01). rs1333049 polymorphism was strongly associated with MI wodds ratio (OR) 1.48, 95% confidence interval (CI) 1.22-1.79x after adjusting for traditional risk factors. Although longer hospitalization stay was observed in patients with the rs1333049-C allele, this polymorphism was not related to angiographic severity of CAD, LVEF, and occurrence of MACE after MI. Conclusions: This study demonstrates an association of rs1333049 polymorphism locus on chromosome 9p21 with risk for MI, but not with post-MI prognosis in Han Chinese. Clin Chem Lab Med 2009;47:917-22.

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“…13 It appears that 9p21 region is less important for subclinical atherosclerosis, but rather for the promotion of plaque formation. 8,9,[11][12][13]31 Thus, we saw the rationale to investigate 9p21 rs10757278 with CP presence in patients undergoing carotid endarterectomy. According to our knowledge, this is the first study of 9p21 with advanced carotid stenosis >70% and the first one conducted in South-Eastern European population.…”

Section: Discussionmentioning

confidence: 99%

“…The results were conflicting. [7][8][9][10][11][12] So far, there is only one study, which has proved an association of 9p21 polymorphism rs1333049 with severe CA. 13 The 9p21 polymorphism rs10757278 (c. 22114477A > G) that is in total linkage disequilibrium (LD) with rs1333049 was the only one independently associated with CAD after the adjustment for the effect of other significantly associated single nucleotide polymorphisms (SNPs) from the 9p21 region.…”

Section: Introductionmentioning

confidence: 99%

9p21 locus rs10757278 is associated with advanced carotid atherosclerosis in a gender-specific manner

Zivotic

Stanković

Djordjevic

et al. 2016

Exp Biol Med (Maywood)

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Single nucleotide polymorphisms from the chromosome locus 9p21 are reported to carry a risk for various cardiovascular diseases. One of the lead single nucleotide polymorphisms, rs10757278, was mostly investigated in association with coronary artery disease but rarely with carotid atherosclerosis. In this study, we aimed to analyze the association of rs10757278 A/G polymorphism with carotid plaque presence in advanced carotid atherosclerosis. The study included 803 participants, 486 patients with high-grade stenosis (>70%) who were undergoing carotid endarterectomy and 317 controls from Serbian population. Genotypes were determined using the real-time polymerase chain reaction. According to the recessive model of inheritance, GG genotype was significantly and independently associated with carotid plaque in females only (odds ratio 2.42, CI ¼ 1.20-4.90, P ¼ 0.013). Odds ratio was adjusted for age, body mass index, hypertension, TC, LDLC, HDLC and TG, and P value was corrected for multiple comparisons. Our preliminary findings suggest a gender-specific association of rs10757278 polymorphism with carotid plaque. Further studies on larger sample and in genetically and environmentally similar populations are needed.

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Coronary Artery Disease–Associated Locus on Chromosome 9p21 and Early Markers of Atherosclerosis

Cited by 80 publications

References 29 publications

A myocardial infarction genetic risk score is associated with markers of carotid atherosclerosis

A myocardial infarction genetic risk score is associated with markers of carotid atherosclerosis

Chromosome 9p21 polymorphism is associated with myocardial infarction but not with clinical outcome in Han Chinese

9p21 locus rs10757278 is associated with advanced carotid atherosclerosis in a gender-specific manner

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