Variant on 9p21 strongly associates with coronary heart disease, but lacks association with common stroke

Lemmens, Robin; Abboud, Shérine; Robberecht, Wim; Vanhees, Luc; Pandolfo, Massimo; Thijs, Vincent; Goris, An

doi:10.1038/ejhg.2009.42

Cited by 42 publications

(38 citation statements)

References 37 publications

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“…15 All patients from the Leuven Stroke Genetics Study underwent brain imaging (MRI in Ͼ91% of patients and CT in the remainder) and a standardized protocol including laboratory examination, carotid ultrasound or CT angiography, and cardiac examination (transesophageal echocardiography or transthoracic echocardiography and Holter). Control subjects were selected from the same population and were either spouses of patients with multiple sclerosis, amyotrophic lateral sclerosis or stroke, or healthy community-dwelling subjects, for whom stroke-free status was ensured in 89%.…”

Section: Austria: Graz With Controls From Austrian Stroke Prevention mentioning

confidence: 99%

The Association of the 4q25 Susceptibility Variant for Atrial Fibrillation With Stroke Is Limited to Stroke of Cardioembolic Etiology

Lemmens

Buysschaert

Geelen

et al. 2010

Stroke

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Background and Purpose-Genome-wide association studies recently identified 2 variants on chromosome 4q25 as susceptibility factors for atrial fibrillation. Interestingly, these variants were subsequently also shown to be associated with stroke. However, it remains unclear whether 4q25 associates with all the stroke subtypes or with cardioembolic stroke in particular, which is often attributable to atrial fibrillation. Methods-We performed a large case-control association study in 4199 ischemic stroke patients, all subtyped according to Trial of Org 10172 in Acute Stroke Treatment criteria, and 3750 controls derived from 6 studies conducted in Australia, Austria, Belgium, Poland, Spain, and Sweden. Two variants on chromosome 4q25, rs1906591 and rs10033464, were genotyped. Results-Within cases, the A-allele of rs1906591 was associated with atrial fibrillation (odds ratio, 1.64 [95% CI, 1.43 to 1.90]; Pϭ9.2 ⅐ 10 Ϫ12 ), whereas rs10033464 was only marginally associated. There was an association between overall ischemic stroke and rs1906591 (odds ratio, 1.20 [95% CI, 1.09 to 1.32]; Pϭ1.2 ⅐ 10 Ϫ4 ). However, this was probably caused by the large effect of stroke of cardioembolic etiology because no relation was obtained in any other subgroup of stroke. The rs10033464 variant failed to show any relationship with ischemic stroke. Conclusions-We replicated the association of the rs1906591 variant on chromosome 4q25 with atrial fibrillation and ischemic stroke of cardioembolic etiology. The 4q25 locus failed to associate with noncardiac subtypes of ischemic stroke. (Stroke.

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Section: Austria: Graz With Controls From Austrian Stroke Prevention mentioning

confidence: 99%

The Association of the 4q25 Susceptibility Variant for Atrial Fibrillation With Stroke Is Limited to Stroke of Cardioembolic Etiology

Lemmens

Buysschaert

Geelen

et al. 2010

Stroke

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“…[5][6][7][8][9][10][11][12] A recent meta-analysis 13 showed that the association of 9p21.3 with stroke is only confined to the subtype of large-vessel strokes. However, a recent genome-wide association study showed that the 9p21.3 region is also implicated in risk for intracranial aneurysm, in which atherosclerosis is not thought to play a major role.…”

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confidence: 99%

Variants on Chromosome 9p21.3 Correlated With ANRIL Expression Contribute to Stroke Risk and Recurrence in a Large Prospective Stroke Population

Zhang

Chen²,

Liu³

et al. 2012

Stroke

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Background and Purpose-ANRIL encodes a long antisense noncoding RNA in the INK4 locus. Although ANRIL has been proven to be associated with coronary heart disease, its roles in stroke are inconsistent, and sparse data are available regarding hemorrhagic stroke. Methods-A Chinese case-control study was conducted, comprising 1657 cases (724 atherothrombosis, 466 lacunar infarction, and 462 hemorrhagic strokes) and 1664 controls. Stroke patients were prospectively followed-up for a median of 4.5 (range, 0.1-6.0) years. Expression of ANRIL transcripts was examined in 42 human atherosclerotic plaques. Results-After adjustment for vascular risk factors and correction for multiple comparisons, subjects carrying the GG genotype of rs10757278 had 1.47-fold (95% CI, 1.11-1.89; Pϭ0.05) and 1.60-fold (95% CI, 1.16 -2.15; Pϭ0.04) increased risk for atherothrombotic and hemorrhagic strokes, respectively. During the follow-up, 317 recurrent strokes and 301 deaths from all causes were documented. Subjects carrying rs10757278GG had higher risk for stroke recurrence (relative risk [RR],1.56; 95% CI,1.15-2.12; Pϭ0.005) and cardiovascular mortality (RR, 2.0; 95% CI, 1.26 -3.18; Pϭ0.003), respectively. Rs10757274 was also associated with stroke risk and recurrence. Family history of stroke further increased the stroke risk by 2.37-fold (95% CI, 1.38 -4.06; Pϭ0.01) and recurrent stroke risk by 2.45-fold (95% CI, 1.56 -3.86; PϽ0.0001) respectively, when compared with those carrying none of G-alleles and without family history. Finally, rs10757278 was associated with differential expression of the ANRIL transcripts. Conclusions-Our findings indicated that the ANRIL may serve as a novel genetic marker for the risk of atherothrombotic and hemorrhagic stroke and their recurrence. (Stroke. 2012;43:14-21.)Key Words: chromosome 9p21.3 Ⅲ follow-up studies Ⅲ genetics Ⅲ risk factors S troke is a major cause of death and disability worldwide and in China. Survivors are often disabled, require long-term care, and are at high risk of recurrence. Among subtypes of stroke, hemorrhagic stroke accounts for 20% to 40% in the Chinese population; in contrast, the majority (80 -90%) of strokes are cerebral infarctions in most western populations. 1 The reasons for high risk of stroke, especially hemorrhagic stroke, among the Chinese, remain unknown. The contribution of genetic risk to stroke is still not completely understood.It is generally accepted that genetic variants on chromosome 9p21.3 are associated with the risk of coronary artery disease, 2-4 but its roles in stroke are inconsistent. [5][6][7][8][9][10][11][12] A recent meta-analysis 13 showed that the association of 9p21.3 with stroke is only confined to the subtype of large-vessel strokes. However, a recent genome-wide association study showed that the 9p21.3 region is also implicated in risk for intracranial aneurysm, in which atherosclerosis is not thought to play a major role. 14 Therefore, additional studies are needed to determine the mechanisms by which the 9p21.3 region affects vascular...

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“…It is possible that hormonal factors, increased exposure to important risk factors, genetic susceptibility, or a combination of these variables may contribute to this phenomenon. Our finding is interesting because the SNP rs10757278 has also been found to be associated with cardiovascular diseases (CAD) [11,12,22] , diabetes [22] , and intracranial aneurysm [23] . We have applied Bonferroni's test to our data analyses.…”

Section: Discussionmentioning

confidence: 78%

“…They found that this SNP, tagged as rs10757278, contributed to the risk of myocardial infarction and intracranial aneurysm. Two other recent independent population-based case-control studies have also shown that the rs10757278 SNP is significantly associated with coronary heart disease and related disorders among Europeans [11,12] . The previous studies have found associations between these SNPs and abdominal aortic aneurysm, but only in populations of European descent.…”

Section: Introductionmentioning

confidence: 80%

Genetic analysis of six SNPs in candidate genes associated with high cross-race risk of development of thoracic aortic aneurysms and dissections in Chinese Han population

et al. 2010

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Aim: Genetic susceptibility is an important risk factor for aortic aneurysm and dissection. Recent case-control association studies have identified six single nucleotide polymorphisms (SNPs) associated with abdominal aortic aneurysm (AAA) in a Caucasian population. We aimed to determine whether these loci confer susceptibility to thoracic aortic dissection (TAD) in a Chinese Han population and thus to establish cross-race susceptibility to TAD. Methods: This study analyzed blood DNA isolated from 206 TAD patients and 180 controls from the ethnic Chinese Han population. Six SNPs -rs819146, rs8003379, rs2853523, rs326118, rs3788205, and rs10757278 -were genotyped using high-throughput matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. Results: The A allele frequency for the SNP on 9p21, tagged as rs10757278, was higher in male TAD patients than in male controls (P=0.017). Moreover, with adjustment for traditional cardiovascular risk factors (sex, age, hypertension, dyslipidemia, diabetes, and smoking), the rs10757278 [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.43 to 0.93] polymorphism was found to be an independent susceptibility factor for TAD in men. Conclusion: Our results suggest that a sequence variant on 9p21 is an important susceptibility locus that confers high cross-race risk for development of TAD in Chinese Han population.

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Variant on 9p21 strongly associates with coronary heart disease, but lacks association with common stroke

Cited by 42 publications

References 37 publications

The Association of the 4q25 Susceptibility Variant for Atrial Fibrillation With Stroke Is Limited to Stroke of Cardioembolic Etiology

The Association of the 4q25 Susceptibility Variant for Atrial Fibrillation With Stroke Is Limited to Stroke of Cardioembolic Etiology

Variants on Chromosome 9p21.3 Correlated With ANRIL Expression Contribute to Stroke Risk and Recurrence in a Large Prospective Stroke Population

Genetic analysis of six SNPs in candidate genes associated with high cross-race risk of development of thoracic aortic aneurysms and dissections in Chinese Han population

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