Sequence variant on 9p21 is associated with the presence of Abdominal Aortic Aneurysm disease but does not have an impact on aneurysmal expansion

Department of Cardiovascular Genetics, Rayne Building, UCL, UK.
European journal of human genetics: EJHG (Impact Factor: 4.35). 11/2008; 17(3):391-4. DOI: 10.1038/ejhg.2008.196
Source: PubMed


Abdominal aortic aneurysm (AAA) is among a number of vascular disorders to be recently associated with a common allelic variant situated on chromosome 9p21. To further assess the significance of this region of the genome in AAA development, we genotyped the sequence variation tagged by rs10757278 in two geographically independent cohorts of patients and compared them to matched controls. We also assessed the impact of this variant on AAA growth rate in cohorts with a median surveillance period of 3.2 and 4.5 years. Using meta-analysis to combine the findings of both cohorts, we found a significant association between rs10757278-G and the presence of AAA (OR (95%CI) 1.38 (1.04-1.82) P=0.03), an effect size completely consistent with that originally reported. rs10757278 was not significantly associated with altered AAA growth rate in either cohort.

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Available from: Jonathan Golledge, Oct 02, 2015
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    • "A significant association between rs10757278-G and the presence of AAA was found (P = 0.03), an effect size completely consistent with that originally reported [73]. rs10757278 was not significantly associated with altered AAA growth rate [73]. In a newer study [74], single-nucleotide polymorphisms rs10757278 and rs1333049 of chromosome 9p21-3 region were significantly associated with increased risk of AAA. "
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    ABSTRACT: Abdominal aortic aneurysm (AAA) is a prevalent and potentially life-threatening disease. Early detection by screening programs and subsequent surveillance has been shown to be effective at reducing the risk of mortality due to aneurysm rupture. The aim of this review is to summarize the developments in the literature concerning the latest biomarkers (from 2008 to date) and their potential screening and therapeutic values. Our search included human studies in English and found numerous novel biomarkers under research, which were categorized in 6 groups. Most of these studies are either experimental or hampered by their low numbers of patients. We concluded that currently no specific laboratory markers allow screeing for the disease and monitoring its progression or the results of treatment. Further studies and studies in larger patient groups are required in order to validate biomarkers as cost-effective tools in the AAA disease.
    Full-text · Article · May 2014 · BioMed Research International
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    • "Interestingly, the 9p21.3 locus is also associated with increased risk of abdominal aortic aneurysm [54-56] and intracranial aneurysm [57,58]. Recently, high plasma TGFβ1 levels have been implicated in the manifestation of aortic root dilation in Marfan syndrome [6,13,59]. "
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    ABSTRACT: Background Genetic variations in TGFB1 gene have been studied in relation to coronary heart disease (CHD) risk, but the results were inconsistent. Methods We performed a systematic review of published studies on the potential role of TGFB1 genetic variation in CHD risk. Articles that reported the association of TGFB1 genetic variants with CHD as primary outcome were searched via Medline and HuGE Navigator through July 2011. The reference lists from included articles were also reviewed. Results Data were available from 4 studies involving 1777 cases and 7172 controls for rs1800468, 7 studies involving 5935 cases and 10677 controls for rs1800469, 7 studies involving 6634 cases and 9620 controls for rs1982073, 5 studies involving 5452 cases and 9999 controls for rs1800471, and 4 studies involving 5143 cases and 4229 controls for rs1800472. The pooled odds ratios (ORs) for CHD among minor T allele carriers of rs1800469, minor C allele carriers of rs1982073, and minor C allele carriers of rs1800471 versus homozygous major allele carriers was 1.14 (95% confidence interval [CI]: 1.05-1.24), 1.18 (95% CI: 1.04-1.35), and 1.16 (95% CI: 1.02-1.32), respectively. No substantial heterogeneity for ORs was detected among the included Caucasian populations for all SNPs. However, for rs1800471, the statistical significance disappeared after adjusting for potential publication bias. No significant association was found between rs1800468 and rs1800472 variants and CHD risk. Conclusion Minor allele carriers of two genetic variants (rs1800469 and rs1982073) in TGFB1 have a 15% increased risk of CHD.
    Full-text · Article · May 2012 · BMC Medical Genetics
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    • "It is not clear whether this phenotype has a large heritable component or whether the genes that predispose to AAA are also those that predispose to rapid expansion. For example, it does not appear that the 9p21 SNP associates with expansion rates [36]. It should be noted, however, that genetic studies of expansion have often been small and underpowered, with heterogeneity in the cohorts with regard to how the phenotype is actually measured and modeled, which is a major methodological concern. "
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    ABSTRACT: Abdominal aortic aneurysm (AAA) is a common disease with a large heritable component. There is a need to improve our understanding of AAA pathogenesis in order to develop novel treatment paradigms. Genomewide association studies have revolutionized research into the genetic variants that underpin the development of many complex diseases including AAA. This article reviews the progress that has been made to date in this regard, including mechanisms by which loci identified by GWAS may contribute to the development of AAA. It also highlights potential post-GWAS analytical strategies to improve our understanding of the disease further.
    Full-text · Article · Jan 2012 · Cardiology Research and Practice
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