A single nucleotide polymorphism in exon 3 of the kallikrein 1 gene is associated with large but not small abdominal aortic aneurysm

Abstract

Objective Abdominal aortic aneurysm (AAA) is a late onset degenerative condition with an inherited component thought to be due to multiple risk alleles. A locus on chromosomes 19q13 has been previously associated with AAA. The gene encoding kallikrein 1 ( KLK1) is located on chromosome 19q13 and the single nucleotide polymorphism (SNP) rs5516 has been previously shown to lead to structural changes in the KLK1 transcription regulatory region. The aim of this study was to investigate whether rs5516 was associated with AAA and aortic diameter. Methods We performed a case–control study on two independent subject groups from Western Australia ( n = 1304) and Queensland ( n = 325) of which 609 and 225 had an AAA, respectively. In addition, we analysed RNA extracted from abdominal aortic biopsies from 12 patients undergoing AAA surgery and 6 organ donors. Results After adjusting for other risk factors the G allele of the rs5516 polymorphism was associated with large but not small AAA using a dominant model in the Western Australian men and a recessive model in Queensland subjects. In subjects with large AAA the G allele was associated with aortic diameter. The short splice variant of KLK1 was upregulated within AAA compared to control biopsies. Conclusion This study suggests that a genetic polymorphism in KLK1 may contribute to the risk of developing later stage AAA.