OBJECTIVE: To examine the possible significance of homo- or heterozygous alpha-1-antitrypsin deficiency in the pathogenesis of aortic aneurysms (AA). DESIGN: Prospective investigation. SETTING: University hospital. PATIENTS: 300 controls representing the general population in our region of Southern Germany and 126 patients with aneurysmectomy and graft insertion. METHODS: The alpha-1-antitrypsin phenotype was determined by employing isoelectric focusing. Each patient was also evaluated for hypertension, lipometabolic dysfunction, smoking, hyperuricemia, and diabetes mellitus. MAIN OUTCOME MEASURES: The frequency and distribution of alpha-1-antitrypsin phenotypes and risk factors. RESULTS: 115 of 126 patients presented with one or several of the conventional risk factors: hypertension (61.5%), lipometabolic dysfunction (36.9%), smoking (58.4%), hyperuricemia (13.8%), or diabetes mellitus (6.9%). The following frequencies of alpha-1-antitrypsin phenotypes were determined: PiMM (82.5%), PiMV (4.7%), PiML (1.5%), PiMS (7.1%), PiSS (0.7%), PiMZ (3.0%). Indeed, when compared to the general population (control group) the percentage of the normal PiMM phenotypes was lower in the group of patients with AA (p<0.001). However, in our study this significant difference was not primarily due to the presence of patients homozygous or heterozygous for deficiency alleles PiMS, PiSS and PiMZ (p=0.0523) as has been previously reported, but rather to the high prevalence of the variants PiMV (p<0.005). CONCLUSIONS: Our study suggests that not only Pi-deficiency alleles, previously identified as being associated with AA, but also that Pi variants may play a pivotal role in the pathogenesis of AA.
OBJECTIVE: To examine the possible significance of homo- or heterozygous alpha-1-antitrypsin deficiency in the pathogenesis of aortic aneurysms (AA). DESIGN: Prospective investigation. SETTING: University hospital. PATIENTS: 300 controls representing the general population in our region of Southern Germany and 126 patients with aneurysmectomy and graft insertion. METHODS: The alpha-1-antitrypsin phenotype was determined by employing isoelectric focusing. Each patient was also evaluated for hypertension, lipometabolic dysfunction, smoking, hyperuricemia, and diabetes mellitus. MAIN OUTCOME MEASURES: The frequency and distribution of alpha-1-antitrypsin phenotypes and risk factors. RESULTS: 115 of 126 patients presented with one or several of the conventional risk factors: hypertension (61.5%), lipometabolic dysfunction (36.9%), smoking (58.4%), hyperuricemia (13.8%), or diabetes mellitus (6.9%). The following frequencies of alpha-1-antitrypsin phenotypes were determined: PiMM (82.5%), PiMV (4.7%), PiML (1.5%), PiMS (7.1%), PiSS (0.7%), PiMZ (3.0%). Indeed, when compared to the general population (control group) the percentage of the normal PiMM phenotypes was lower in the group of patients with AA (p<0.001). However, in our study this significant difference was not primarily due to the presence of patients homozygous or heterozygous for deficiency alleles PiMS, PiSS and PiMZ (p=0.0523) as has been previously reported, but rather to the high prevalence of the variants PiMV (p<0.005). CONCLUSIONS: Our study suggests that not only Pi-deficiency alleles, previously identified as being associated with AA, but also that Pi variants may play a pivotal role in the pathogenesis of AA.
Authors: Farouk Dako; Huaqing Zhao; Alexandra Mulvenna; Yogesh Sean Gupta; Scott Simpson; Friedrich Kueppers Journal: Mayo Clin Proc Innov Qual Outcomes Date: 2021-04-30