Restriction fragment length polymorphism of the apoprotein A-I-C-III gene cluster in control and stroke-prone white and black subjects: racial differences.

Abstract

Background and Purpose:The presence of known restriction fragment length polymorphisms in the apoprotein A-I-C-III gene cluster, which encodes their respective apoproteins, was investigated using the restriction enzymes Sac I and Pst I to determine the potential role of genetic variations for stroke risk in an American population.Methods: Ninety-eight subjects (70 white, 28 black subjects), both normal controls with no carotid stenosis and those with carotid stenosis believed at risk for stroke, defined as showing stenosis focally or diffusely at that site, composed the study population.Results: Sac I polymorphic 52 allele frequency was higher in stroke-risk groups, whereas Pst I polymorphic P2 allele frequency was similar in control and stroke-risk groups. Significantly higher levels of serum cholesterol, triglycerides, and low density lipoprotein (p<0.05) and significantly lower levels of high density lipoprotein (p<0.05) were observed in stroke-risk groups with diffuse stenosis. Results of our study with the two racial groups show the following: the frequency of Sac I polymorphism was significantly higher in American black compared with American white subjects (x 2 =3.92, p<0.05). Among serum lipids, triglycerides were significantly higher in white compared with black subjects (p<0.05). In white subjects, carotid artery stenosis was associated with significantly elevated total cholesterol and low density lipoprotein (p<0.01) but not with Sac I polymorphism. In black subjects the converse was observed, namely, the Sac I polymorphic S2 allele seemed to be associated with carotid bifurcation stenosis but did not reach statistical significance because of the small number of subjects. In addition, Sac I polymorphism did not correlate with any lipid profile. Pst I polymorphism was not associated with any lipid profile or carotid artery stenosis abnormalities.Conclusions: Our results indicate that carotid artery stenosis identifies white subjects with increased plasma total cholesterol and low density lipoprotein, an atherogenic profile, but not with Sac I polymorphism. These findings suggest that carotid bifurcation stenosis in white subjects is associated with an atherogenic lipid profile but not with apoprotein A-I-C-III restriction fragment length polymorphisms. In black subjects, Sac I polymorphism seems to identify those individuals with significant carotid stenosis, a necessary precursor to atherothrombotic brain infarction, but not those with elevated total cholesterol, elevated low density lipoprotein, and/or reduced high density lipoprotein. These results suggest that Sac I polymorphism may identify black subjects at increased risk for atherothrombotic brain infarctions.

The importance of family history in cerebrovascular disease.

“…More recent studies have shown an association between dyslipidemic states and cerebrovascular disease. 61 - 62 We found that a history of previously diagnosed dyslipidemia was significantly more prevalent among the stroke population than the control subjects and was an independent risk factor in the multivariate analysis. A detailed report of the lipid profiles of the patients and control subjects is being prepared.…”

Light-to-Moderate Alcohol Consumption and the Risk of Stroke among U.S. Male Physicians

“…52 Another explanation for the effect of alcohol on the risk of stroke is the finding that alcohol increases HDL cholesterol levels, 53,54 which are inversely related to arteriosclerosis at many sites, including the carotid arteries. 41,55 HDL cholesterol levels are lower in survivors of stroke than in controls. [56][57][58] However, changes in HDL cholesterol levels only partially explain the inverse relation between alcohol consumption and death from cardiovascular causes.…”

Pathogenesis of Atherothrombotic Brain Infarction: Role of Lipids

“…Whether the dynamic process of plaque formation at the carotid bifur cation is due to lipid or coagulation/plalelet aggregation defects, Grolta et al [25] reported a significant increase in carotid stenosis of 2:23% over 30 m on th s was associated with a significant increase in LD L. In addition, evaluation of the dynamic aspects of L D L and IID L metabolism by assessing in vivo metabolism o f autologously labelled lipoproteins demonstrated a slower catabolism of LD L and a faster one for I IDL, suggesting that increased resi dent lime in serum combined with enhanced catabolism of H D L is associated with ABls [26], In addition to metabolic parameters supporting the role o f impaired or abnormal cholesterol transport in ABls, altered gene function for proteins involved in cho lesterol metabolism may likely play an important role in determining ABI susceptibility. For example, in a study of gene polymorphism o f the major apoprotein of I IDL, Kasturi et al [27] reported on the occurrence of restric tion fragment length polymorphism (RFLP) of the tandemly arranged apoproteins of A l, ( 'III, and AIV on the long arm o f chromosome 11. Results of the study demon strated that black subjects with extracranial occlusive dis ease display significant R FLP, although while subjects did not.…”