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

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.