Interaction between fibrillin genotype and blood pressure and the development of aneurysmal disease.
Debate as to whether abdominal aortic aneurysms (AAA) are caused by atherosclerosis or whether they have a strong genetic etiology continues. We have investigated the hypothesis that risk factors are likely to be strongest in patients with generalized aneurysmal disease. We screened 232 consecutive AAA patients for popliteal aneurysm and investigated cardiovascular and genetic risk factors in these patients. Ultrasonography demonstrated the presence of a popliteal aneurysm in 24 of 232 (10%) patients. Multivariate analysis identified four independent factors associated with popliteal aneurysm: age (p = 0.013), height (p = 0.017), triglyceride concentration (p = 0.009), and systolic blood pressure (p = 0.037). In the AAA patients a significant association of fibrillin-1 genotype was present, determined by a tandem repeat polymorphism, with both systolic and pulse pressure. The genotypes associated with the highest pressures were significantly more common among the patients with popliteal aneurysm, p = 0.03. Following these findings we investigated whether there was an association between fibrillin-1 genotype and blood pressure in a healthy population, 245 men aged 50-61 years. Again we found a significant association between fibrillin genotype and pulse pressure, p = 0.003. We suggest that a strong interaction occurs between fibrillin genotype and blood pressure which contributes to the development of aneurysmal disease.
Powell
J T
JT
Charing Cross & Westminster Medical School, London, United Kingdom. rahk700@S1.CXWMS.ac.uk
MacSweeney
S T
ST
Greenhalgh
R M
RM
Turner
R J
RJ
Henney
A M
AM
D000375:Aging / Q000378:metabolism; D000783:Aneurysm / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D017544:Aortic Aneurysm, Abdominal / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D001161:Arteriosclerosis / Q000150:complications; D001794:Blood Pressure / Q000235:genetics*; D001827:Body Height; D015897:Comorbidity; D004252:DNA Mutational Analysis; D004547:Elastic Tissue / Q000378:metabolism / Q000473:pathology; D000071838:Fibrillin-1; D000071837:Fibrillins; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000453:epidemiology; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics; D008403:Mass Screening; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology; D011150:Popliteal Artery / Q000000981:diagnostic imaging; D012091:Repetitive Sequences, Nucleic Acid; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology; D013599:Systole; D013718:Tensile Strength; D014280:Triglycerides / Q000097:blood; D014463:Ultrasonography; D054392:Adipokines
D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D014280:Triglycerides; C000605722:FBN1 protein, human; D054392:Adipokines