Association Studies Of ABCA1R219K And LIPC-250G/A Genetic Variants With Late-onset Alzheimer’s Disease

Objective Accumulating evidence suggests that dysregulation of cholesterol homeostasis may be a major etiologic factor in initiating and promoting neurodegeneration in Alzheimer’s disease. ATP-binding cassette transporter A1(ABCA1) and hepatic lipase (HL, coding genes named LIPC) are important components of cholesterol metabolism implicated in atherosclerosis and neurodegenerative diseases. In the present study, we will investigate the possible association of several common loci single-nucleotide polymorphisms(ABCA1R219K and LIPC-250G/A) with susceptibility to AD and plama lipid levels.Methods As a case-control study, a total of sporadic104AD patients and104individuals aged above60years without cognitive impairment enrolled from a population of Chinese Han nationality in Changsha area randomly were studied to determine the polymorphisms of ABCA1R219K and LIPC-250G/A using restriction fragment length polymorphism (RFLP) amplified by polymerase chain reaction (PCR). Adopt SPSS13.0for statistical analysis.Results1. The levels of diastolic blood pressure and TC, the percentages of history of hyperlipidemia in AD group were higher than that in controls, whereas HDL-C level was lower than that of controls(P<0.05).2. There were significant differences in the frequencies of genotype distributions of ABCA1R219K and LIPC-250G/A between the AD patients and controls(x2=8.777, P=0.012and x2=1.925, P=0.019, respectively). The frequency of KK genotype in AD group is obviously lower than that of controls(x2=5.261, P=0.022). The frequency of KK+RK genotype in AD patients is54.8%, is significantly lower than that of controls (70.2%,P=0.022). Compared with controls, the frequency of GG genotype of LIPC-250G/A polymorphism is obviously higher in AD patients (27.9%&13.5%, x2=5.233, P=0.022), while the frequency of GA+AA genotype significantly lower in cases (72.1%&86.5%, P=0.016). There were no significant differences in the comparison of allele frequencies.3. There was significantly higher levels of HDL-C、apoA-I and cognitive scores in the carriers of KK genotype and K allele(P<0.05). In all serum lipids, only apoA-I has been found distinct relevance with LIPC-250G/A. The level of apoA-I was highest in AA genotype, followed by GA and GG genotypes in total subjects. The subjects carrying A allele had higher plasma apoA-I level than non-carriers in both whole population and the control group.4. We examined the association of the two polymorphisms with age-on-set of AD cases, but found no significant association (P>0.05). There was significantly higher levels of MMSE and WMS scores in the carriers of KK genotype and K allele(P<0.05) and subjects carrying LIPC-250A allele obtained higher WMS scores than non-carriers in total population. However, no significant association was observed in AD group or controls. Further in accordance with memory types including long-term memory, short-term memory, transient memory, compared with RR genotype, the scores of short-term memory, transient memory of RK、KK and RK+KK genotypes were higher (P<0.05), but there was no significant difference in the score of long-term memory (P>0.05). Compared with GG genotype, the scores of short-term memory of HL GA+AA genotypes were higher (P<0.05), but there was no significant difference in the score of long-term memory and transient memory (P>0.05). In the study population, there was no significant difference in the scores of WCST among these two loci polymorphisms.5. After adjusting other factors like gender, age and education, multi-factor logistic regression analysis showed that age was an independent risk factor for AD, while carrying K allele or A allele and higher education may produce protective effect on AD.Conclusion The gene variants of ABCA1R219K and LIPC-250G/A are associated with AD. Carrying K allele or A allele may. play a protective role in serum lipids and cognition, and decrease risk of AD.