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Association of an allele on chromosome 9 and abdominal aortic aneurysm.

ABSTRACT: Abdominal aortic aneurysm (AAA) has been recognized as a multi-factorial disease with both genetic and environmental risk factors. A locus residing within non-coding DNA on chromosome 9p21.3 has recently been associated with AAA. To further investigate the significance of this site for AAA, we performed an association study on a large group of 3371 men aged 65-83 years of whom 513 had an AAA.All men were assessed for other risk factors in a uniform way and an ultrasound of the abdominal aorta was performed.Our findings validated the strong association of the chromosome 9p21.3 SNPs rs10757278 and rs1333049 with AAA and demonstrated the upregulation of LINE-1 elements at the site of AAA.This study confirms a reproducible association between risk alleles on chromosome 9p21.3 and AAA. We also provide preliminary evidence for an association of LINE-1 elements with AAA which will require further investigation.

SUBMITTER: Biros E

PROVIDER: S-EPMC2952706 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Association of an allele on chromosome 9 and abdominal aortic aneurysm.

Biros Erik E Cooper Matthew M Palmer Lyle J LJ Walker Philip J PJ Norman Paul E PE Golledge Jonathan J

Atherosclerosis 20100615 2

<h4>Objective</h4>Abdominal aortic aneurysm (AAA) has been recognized as a multi-factorial disease with both genetic and environmental risk factors. A locus residing within non-coding DNA on chromosome 9p21.3 has recently been associated with AAA. To further investigate the significance of this site for AAA, we performed an association study on a large group of 3371 men aged 65-83 years of whom 513 had an AAA.<h4>Methods</h4>All men were assessed for other risk factors in a uniform way and an ul ...[more]

PMID: 20605023

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Association of PPARgamma allelic variation, osteoprotegerin and abdominal aortic aneurysm.

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Genes and abdominal aortic aneurysm.

Project description:Abdominal aortic aneurysm (AAA) is a multifactorial disease with a strong genetic component. Since the first candidate gene studies were published 20 years ago, approximately 100 genetic association studies using single nucleotide polymorphisms (SNPs) in biologically relevant genes have been reported on AAA. These studies investigated SNPs in genes of the extracellular matrix, the cardiovascular system, the immune system, and signaling pathways. Very few studies were large enough to draw firm conclusions and very few results could be replicated in another sample set. The more recent unbiased approaches are family-based DNA linkage studies and genome-wide genetic association studies, which have the potential of identifying the genetic basis for AAA, only when appropriately powered and well-characterized large AAA cohorts are used. SNPs associated with AAA have already been identified in these large multicenter studies. One significant association was of a variant in a gene called contactin-3, which is located on chromosome 3p12.3. However, two follow-up studies could not replicate this association. Two other SNPs, which are located on chromosome 9p21 and 9q33, were replicated in other samples. The two genes with the strongest supporting evidence of contribution to the genetic risk for AAA are the CDKN2BAS gene, also known as ANRIL, which encodes an antisense ribonucleic acid that regulates expression of the cyclin-dependent kinase inhibitors CDKN2A and CDKN2B, and DAB2IP, which encodes an inhibitor of cell growth and survival. Functional studies are now needed to establish the mechanisms by which these genes contribute toward AAA pathogenesis.

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