Effects Of ABCA1, PON1 And ApoE Gene Polymorphisms On Plasma Lipid Levels And Cerebrovascular Disease

Chapter 1Study of the Relationship Between Gene PolymorphisminABCA1 and StrokeBackground: The ABCA1 gene, a member of the ATP-binding cassette A transporter superfamily, encodes a membrane protein that facilitates the cellular efflux of cholesterol and phospholipids. Mutations in ABCA1 lead to familial high-density lipoprotein deficiency and Tangier disease. ABCA1 R219K gene polymorphism is common genetic variation, which is associated with decreased TG, increased HDL-C, decreased progression of atherosclerosis and reduced risk of coronary events. It is suggested that ABCA1 R219K is candidate protective gene for strokes.Objective: To investigate the correlation between stroke and common genetic variants in ABCA1.Method: This was a case-control study, which enrolled 313 cases with cerebral hemorrhage, 379 cases with cerebral infarction and 351 controls without CHD and CVD. Polymerase chain reaction-restricted fragments length polymorphism was used to determine ABCA1 genotype.Results:1. The ABCA1R219K genotype distribution in Hunan Province China was RR31.9%, RK49.0% and KK19.1%, respectively. Allele frequencies for R and K were 56.4%, 43.6% respectively.2. The ABCA1R219K allele and genotype distribution among three groups showed a significant difference. RR genotype frequencies showed a higher frequency in both cerebral hemorrhage group and cerebral infarction compared to control (P<0.05). The genotype frequencies of R219K for cerebral hemorrhage were not consistent with Hardy-Weinberg equilibrium3. The levels of HDL-C among RR, RK and KK genotype tended downward respectively. The were significant differences between RR genotype and KK genotype. The levels of TG tended upward respectively, but there were no significant differences each other.4. Linear regression analysis showed that HDL-C was positively correlated with age in RR noncarriers and TC was negatively correlated with age in carriers. In age 65 of the cohort, the levels of HDL-C were higher in carriers than in noncarriers.5. The RK+KK genotype had an independent protective effect on stroke, (cerebral hemorrhage: OR=0.634,95%CI0.462-0.871,P=0.005; cerebral infarction: OR=0.732, 95%CI 0.533-0.981, P=0.037. )Conclusion: This is the first observation of ABCAl R219K common genetic variants distribution in Chinese people. The K allele frequency showed a higher frequency in Chinese compared in Europeans. There were significant differences in R219K genotype among three groups. The carriers results in a beneficial profile of blood lipids, RK+KK genotype is more pronounced in age 65 individuals. The RK+KK genotype had an independent protective effect on strokes.