Influence of apolipoproteins on the anatomical distribution of arterial disease.
The association of raised triglyceride levels with peripheral arterial disease has indicated that different interactions of environmental, biochemical and genetic risk factors promote atherosclerosis in particular sites. This hypothesis was investigated in patients presenting with atherosclerotic disease in the carotid (n = 23) or peripheral arteries (n = 94) before the age of 50 years; symptomatic coronary artery disease was also present in some patients (n = 35). Patients presenting with carotid disease had the highest levels of cholesterol (mean 7.6 mmol/l, P less than 0.05), apolipoproteins B (mean 1.02 g/l) and CIII (median 22.8 mg/dl, P less than 0.05) but normal levels of apolipoprotein AI. Patients presenting with peripheral arterial disease were the heaviest smokers and this was the only group where hypertriglyceridaemia was observed. Patients with coronary artery disease had the lowest levels of apolipoprotein AI (mean 1.15 g/l, P less than 0.05). Although polymorphic variation in the apolipoprotein genes did not appear to influence the distribution of symptomatic disease, genetic variation at two polymorphic sites in the apolipoprotein AI-CIII-AIV gene cluster was associated with differences in triglyceride levels. The control of the metabolism of triglyceride rich particles by apolipoproteins may predispose to atherosclerosis in specific sites, low levels of apolipoprotein AI selectively promoting coronary artery atherosclerosis and high levels of apolipoprotein CIII selectively promoting carotid artery atherosclerosis.
Department of Surgery, Charing Cross & Westminster Medical School, London, U.K.
S A
SA
Wiseman
J T
JT
Powell
N
N
Barber
S E
SE
Humphries
R M
RM
Greenhalgh
D000328:Adult; D016632:Apolipoprotein A-I / Q000032:analysis / Q000235:genetics; D053305:Apolipoprotein C-III; D001053:Apolipoproteins / Q000032:analysis / Q000235:genetics*; D001056:Apolipoproteins C / Q000032:analysis / Q000235:genetics; D001161:Arteriosclerosis / Q000097:blood / Q000235:genetics / Q000473:pathology*; D002340:Carotid Artery Diseases / Q000097:blood / Q000235:genetics; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length
D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001053:Apolipoproteins; D001056:Apolipoproteins C; D017270:Lipoprotein(a); D008074:Lipoproteins