DNA restriction polymorphisms of the apolipoprotein AI-CIII-AIV gene cluster: a genetic determinant of atherosclerosis in type 2 (non-insulin-dependent) diabetes mellitus.
The presence of polymorphic restriction sites (S2, M2, P2) of the apolipoprotein AI-CIII-AIV gene cluster for the respective Sst1, Msp1, and Pst1 enzymes was assessed after hybridization with a radiolabelled apolipoprotein AI gene probe in 64 Type 2 diabetic patients and 67 healthy control subjects, all Europids. Twenty-two diabetic patients showed evidence of ischaemic heart disease or macrovascular arteriopathy and forty-two were free of cardiovascular complications. Control subjects were selected for the absence of personal or familial metabolic or cardiovascular diseases. The frequencies of polymorphic alleles were in agreement with previous studies in the control group: S2 6.3 (95% confidence interval (CI) 2.3-10.3) %, M2 5.5 (1.6-9.4) %, P2 6.3 (2.3-10.3) % and did not differ in the whole diabetic group: S2 4.2 (0.7-7.7) %, M2 6.5 (2.0-11.0) %, P2 6.6 (2.3-10.9) %. The relative prevalences of S2, M2, and P2 alleles were, respectively: 3.32, 1.54, and 2.00 (Woolf's ratio) in the macroangiopathic group but allele distribution frequencies were not statistically different from non-macroangiopathic patients. The allelic associations S2M2P1 and S1M1P2 showed a relative prevalence of 2.86 and 2.00 in the presence of cardiovascular complications but the difference was not significant in terms of polyallelic distribution frequencies in the absence of atherosclerosis. No serum lipid abnormalities could be related to the presence of any polymorphic allele or allelic association. These results suggest a genetic influence on the development of atherosclerosis in Type 2 diabetes, but the mechanism remains unclear.
Clinique des Maladies Métaboliques et Endocriniennes, Hôpital Lapeyronie, Montpellier, France.
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Renard
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Dupuy
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Monnier
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Crastes de Paulet
D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A / Q000097:blood / Q000235:genetics*; D001056:Apolipoproteins C / Q000235:genetics*; D001161:Arteriosclerosis / Q000097:blood / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000097:blood / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D008075:Lipoproteins, HDL / Q000235:genetics*; D005810:Multigene Family; D012150:Polymorphism, Restriction Fragment Length; D015183:Restriction Mapping; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; D001056:Apolipoproteins C; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D014280:Triglycerides; C022205:apolipoprotein A-IV; D004247:DNA