Background: Abdominal aortic aneurysm (AAA) is a complex disorder in which environmental and genetic factors play a role in pathogenesis. Linkage to 2 adjacent loci on 19q13 in familiar AAA was previously demonstrated. We studied whether genetic variation within these regions predisposes to AAA. Methods: Common genetic variants in the described regions on 19q13 were analyzed using tag single nucleotide polymorphisms (SNPs) in a Dutch case-control population. Single nucleotide polymorphism genotyping was performed in a 2-stage approach. Results: In stage 1, 615 SNPs were genotyped in 376 AAA patients and 648 controls. In stage 2, 8 SNPs of stage 1 with a P value < .015 were genotyped in a second independent cohort of 360 cases and 376 controls. No differences in allele frequencies were observed. Conclusion: Our findings suggest that there are no common AAA predisposing SNPs within the 19q13 loci. Hence, the genetic basis of familiar and sporadic AAA may differ.
Sakalihasan N., Limet R., Defawe ODAbdominal aortic aneurysm. Lancet. 2005;365(9470):1577-1589.
2.
Cornuz J., Sidoti PC, Tevaearai H., Egger M.Risk factors for asymptomatic abdominal aortic aneurysm: systematic review and meta-analysis of population-based screening studies. Eur J Public Health. 2004;14(4):343-349.
3.
Sandford RM, Bown MJ, London NJ, Sayers RDThe genetic basis of abdominal aortic aneurysms: a review. Eur J Vasc Endovasc Surg. 2007;33(4):381-390.
4.
Annambhotla S., Bourgeois S., Wang X., Lin PH, Yao Q., Chen C.Recent advances in molecular mechanisms of abdominal aortic aneurysm formation. World J Surg. 2007;32:976-986.
van der Graaf Y., Akkersdijk GJ, Hak E., Godaert GL, Eikelboom BCResults of aortic screening in the brothers of patients who had elective aortic aneurysm repair. Br J Surg. 1998;85(6):778-780.
7.
Ogata T., Mackean G., Cole CW, et al. The lifetime prevalence of abdominal aortic aneurysms among siblings of aneurysm patients is eightfold higher than among siblings of spouses: an analysis of 187 aneurysm families in Nova Scotia, Canada. J Vasc Surg. 2005;42(5):891-897.
8.
Fitzgerald P. , Ramsbottom D., Burke P., et al. Abdominal aortic aneurysm in the Irish population: a familial screening study. Br J Surg. 1995;82(4):483-486.
9.
Van Vlijmen-Van Keulen CJ, Pals G., Rauwerda JAFamilial abdominal aortic aneurysm: a systematic review of a genetic background. Eur J Vasc Endovasc Surg. 2002;24(2):105-116.
10.
Shibamura H. , Olson JM, van Vlijmen-Van Keulen C., et al. Genome scan for familial abdominal aortic aneurysm using sex and family history as covariates suggests genetic heterogeneity and identifies linkage to chromosome 19q13. Circulation. 2004;109: 2103-2108.
11.
Van Vlijmen-Van Keulen CJ, Rauwerda JA, Pals G.Genome-wide linkage in three Dutch families maps a locus for abdominal aortic aneurysms to chromosome 19q13.3Eur J Vasc Endovasc Surg. 2005;30(1):29-35.
12.
Boll AP, Verbeek AL, van de Lisdonk EH, van der Vliet JAHigh prevalence of abdominal aortic aneurysm in a primary care screening programme . Br J Surg. 1998;85(8):1090-1094.
13.
Akhurst RJA sweet link between TGFbeta and vascular disease?Nat Genet.2006;38(4):400-401.
14.
Daugherty A. , Cassis LAMouse models of abdominal aortic aneurysms . Arterioscler Thromb Vasc Biol. 2004;24(3):429-434.
15.
Middleton RK , Lloyd GM, Bown MJ, Cooper NJ, London NJ, Sayers RDThe pro-inflammatory and chemotactic cytokine microenvironment of the abdominal aortic aneurysm wall: a protein array study . J Vasc Surg. 2007;45(3):574-580.
16.
Choke E., Cockerill GW, Laing K., et al. Whole genome-expression profiling reveals a role for immune and inflammatory response in abdominal aortic aneurysm rupture. Eur J Vasc Endovasc Surg.2009;37(3):305-310.
17.
Helgadottir A. , Thorleifsson G., Magnusson KP, et al. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nat Genet. 2008;40(2):217-224.
18.
Thompson AR, Golledge J., Cooper JA, Hafez H., Norman PE, Humphries SESequence variant on 9p21 is associated with the presence of abdominal aortic aneurysm disease but does not have an impact on aneurysmal expansion. Eur J Hum Genet.2009; 17(3):391-394.
19.
Thompson AR , Drenos F., Hafez H., Humphries SECandidate gene association studies in abdominal aortic aneurysm disease: a review and meta-analysis. Eur J Vasc Endovasc Surg. 2008;35(1):19-30.
20.
Genome Wide Association Studies: identifying the genes that determine the risk of abdominal aortic aneurysm. Eur J Vasc Endovasc Surg. 2008;36(4):395-396.
