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Effects of ApoC3 and ApoA1 Gene Polymorphisms on Plasma Lipid Levels and Cerebrovascular Disease

Author: LuWei
Tutor: ZhaoShuiPing
School: Central South University
Course: Internal Medicine
Keywords: Apolipoprotein C3 Gene polymorphism Lipids Cerebral hemorrhage Cerebral infarction AopA1 ApoA1 ApoC3
CLC: R743.3
Type: PhD thesis
Year: 2006
Downloads: 335
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Abstract


Background: ApoC3 is a major component of triglyceride (TG)-rich lipoproteins (TRLs) and HDL. ApoC3 and serum TG levels are positively correlated. The rare allele of the polymorphic -482C>T in the promoter region of the ApoC3 gene has frequently been associated with raised ApoC3 and TG levels and correlated to CAD.A common G-to-A substitution in the promoter area of the ApoA1 gene has been described. The A allele was shown to be associated with higher HDL-cholesterol concentrations and can decreased progression of atherosclerosis and reduced risk of coronary events. It is suggested that ApoA1-75G>A is candidate protective gene for strokes.The opposing effects of ApoA1 and ApoC3 on triglyceride metabolism are intriguing and clinically relevant. Both the ApoA1 and ApoC3 genes are located in the APOA1-C3-A4 gene cluster. Several polymorphic sites have been identified in this gene cluster, and. have been associated with lipid levels and coronary artery disease. It was not known whether there are interaction between the polymorphic ApoA1-75G>A and ApoC3-482C>T.Objective:1、To investigate the correlation between stroke and common genetic variants in ApoC32、To investigate the correlation between stroke and common genetic variants in ApoA1.3、To explore the association of interaction between ApoC3 gene polymorphisms and common genetic variants in ApoA1 on the presence of strokes.Method: This was a case-control study, which enrolled 209 cases with cerebral hemorrhage, 212 cases with cerebral infarction and 291 controls without CHD and CVD. Polymerase chain reaction-restricted fragments length polymorphism was used to determine ApoA1 genotype.Results:1. The ApoC3-482C>T genotype distribution in the subjects was CC 28%, CT 48% and TT 24%, respectively. Allele frequencies for C and T were 52% and 48%, respectively。2. The ApoC3-482C>T allele and genotype distribution among three groups showed a significant difference. TT genotype frequencies showed a higher frequency in both cerebral hemorrhage group and cerebral infarction compared to control (P<0.05).3. The levels of TG among CC、CT and TT genotype tended upward respectively. The levels of HDL-C in CT and TT was lower than that of CC, there were significant differences each other.4. In CT genotype, the levels of ApoA1 of diabetic patients Was lower than that of the nodiabetic patients. In TT, the levels of TG of diabetic patients was higher than that of the nodiabetic patients, and the levels of HDL-C was lower than that of the nodiabetic patients.5. In the smoking people, the levels of HDL-C was lower in carriers than in noncarriers.6. The CT+TT genotype is positively correlated to cerebral infarction but there are no correlated between ApoC3-482C>T and cerebral hemorrhage, (cerebral hemorrhage: OR=1.082, 95% CI0.752-1.557, P=0.18; cerebral infarction: OR=1.478, 95%CI 1.107-2.150, P=0.038。)7. The ApoA1-75G>A genotype distribution in subjects was GG 58.16%, AG 24.77% and AA 17.07%, respectively. Allele frequencies for G and A were 70.54% and 29.46%, respectively.8. The ApoA1-75G>A allele and genotype distribution among stroke and control showed a significant difference. GG genotype frequencies showed a higher frequency in both cerebral hemorrhage group and cerebral infarction compared to control (P<0.05). AG and AA genotype frequencies showed a higher frequency in control compared to both cerebral hemorrhage group and cerebral infarction (P<0.05).9. The levels of HDL-C in AA was highter than that of GG. (P<0.05). The levels of TC, ApoB, LDL-C, LP(a), HDL-C/TC were no significant differences between AA genotype and GG genotype.10. The AA+AG genotype had an independent effect on cerebral hemorrhage (OR=0.725, 95% CI0.548-1.073, p=0.047); but there are no significant protectively effect, on cerebral infarction (OR=0.805, 95%CI0.501-1.151。)11. The interaction between the polymorphic ApoA1-75G>A and ApoC3-482C>T had not significant effect on the levels of lipid and MBI.12. In the patients with stroke, GG/TT and GG/CT genotype distribution frequency was significant higher than frequencies of AA/CC genotype. In the individuals with stroke family history, A carriers was significant lower than nocarriers (P<0.05). The AA/CC genotype carriers had a lowest frequency of diabetic than other genotype.13. The AA/CC genotype had a protective effect on cerebral infarction (OR=0.205, 95%CI0.101-0.417, P=0.003), but had no protective effect on cerebral hemorrhage (OR=0.987, 95%CI0.741-1.899, P=0.477).Conclusion:1、This is the first observation of common genetic variants distribution of ApoC3 in Chinese people. The T allele frequency showed a higher frequency in Chinese compared in Europeans. There were significant differences in ApoC3-482C>T genotype amorig three groups. The carriers results in a unfavourable of blood lipids, exceptionally in the smoking people and diabetic patients. The CT、TT genotype had an independent unfavourable effect on strokes.2、There were significant differences in ApoA1-75G>A genotype among three groups. The carriers results in a beneficial profile of blood lipids, The AA+AG genotype had an independent protective effect on strokes.3、The result exhibited an interaction of two genes on stroke. The AA/CC genotype had an protective effect on the individuals with stroke family history, diabetic, and had an protective effect on cerebral infarction.

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CLC: > Medicine, health > Neurology and psychiatry > Neurology > Cerebrovascular disease > Acute cerebrovascular disease ( stroke)
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