Association of the KLK1 rs5516 G allele and the ACE D allele with aortic aneurysm and atherosclerotic stenosis

Abstract

Objective:Atherosclerosis underlies aortic aneurysm (AA) and atherosclerotic stenosis (AS). Kallikrein-1 (KLK1) and angiotensin-converting enzyme (ACE) are 2 key molecules in kallikrein-kinin systems and renin-angiotensin systems, respectively, which are responsible for maintaining vascular balance and stability, playing important roles in atherosclerosis. We aimed to assess the involvement of single nucleotide polymorphism rs5516 in KLK1 as well as the insertion/deletion rs4646994 polymorphism in ACE in the development of AA and AS.Methods:We enrolled Chinese Han patients with AA (N = 408) and AS (N = 432), as well as healthy controls (N = 408). Clinical and demographic characteristics were assessed. Genotypes were analyzed with recessive and dominant models.Results:The rs5516 G allele of KLK1 was significantly associated with AA (P < 0.001), and the D allele of ACE was significantly associated with both AA (P < 0.001) and AS (P < 0.001). The GG and DD genotypes were significantly associated with both AA (P = 0.013) and AS (P < 0.001) in a recessive model, and were synergistic with hypertension in AA patients, but not in AS. Patients with CC/DD, CG/ID, or GG/II genotypes, which were synergistic with hypertension, had a greater risk of developing AA, while CC/DD, CG/DD, GG/ID, or GG/DD genotypes, which were not synergistic with hypertension, contributed to the development of AS.Conclusion:The KLK1 rs5516 G allele is closely associated with AA, and the ACE D allele is closely related to AA and AS.

Linking single nucleotide polymorphisms to signaling blueprints in abdominal aortic aneurysms

“…Here, we identified SNP rs5516, a stop-gained mutation for KLK1 (Kallikrein 1), with the highest pathogenicity score and a significantly high frequency in AAA (17.8%). Indeed, previous SNPs studies performed in both Australian and Asian cohorts have shown the association of rs5516 with AAA 30,43 . Our analysis identified other interesting polymorphism profiles associated with significant genes that correlated with AAA.…”

Linking single nucleotide polymorphisms to metabolic risk and matrix remodeling in abdominal aortic aneurysms

“…Here, we identi ed SNPs rs5516, which is a stop-gained mutation for KLK1, had the highest pathogenicity score with a signi cantly high frequency in AAA (17.8%). Indeed, previous SNPs study had shown its association in aortic aneurysm with evidence pointing out the role of KLK1 with proin ammatory and vascular remodeling properties of the aorta 29 . Our analysis identi ed other interesting polymorphism pro les associated with signi cant genes correlated with AAA.…”

“…The SNP rs5516, which codes for KLK1 is a stop-gained mutation. The CG allele of this SNP is 17.8% more expressed in Australian AAA patients than in control groups 29 . The SNP rs1801133, coding for MTHFR is a nonsynonymous mutation, its CT/CC allele is only 3% more expressed in Greek AAA patients than in control 30 .…”