Genetic polymorphisms of lipid metabolism gene SAR1 homolog B and the risk of Alzheimer's disease and vascular dementia.

ABSTRACT

BACKGROUND/PURPOSE: Lipid metabolism is involved in beta amyloid generation, which has been related with the progression of Alzheimer's disease (AD). No study has explored the association between polymorphisms of SAR1 homolog B (SAR1B) and the risk of dementia previously. METHODS: This is a case-control study. A total of 279 AD and 117 vascular dementia (VaD) patients were recruited from neurology clinics at three teaching hospitals in Taiwan from 2007 to 2010. Controls (n = 466) were recruited from the elderly health checkup program and volunteers in the hospital during the same time interval. Three common (frequency ≥ 5%) haplotype-tagging single nucleotide polymorphisms were selected from the lipid metabolism gene SAR1B to assess its association with AD and VaD. RESULTS: Homozygous variants of rs11948613 were associated with a decreased AD risk (CC vs. TT adjusted odds ratio = 0.39, 95% confidence interval = 0.15-0.98) with a population attributable risk of 26.7%. This association decreased further in apolipoprotein E ε4 (ApoE ε4) noncarriers (adjusted odds ratio = 0.28, 95% confidence interval = 0.09-0.91). No association was found for VaD. Two common haplotypes (with a cumulative frequency of 95.7% in controls) were identified for SAR1B, and no association was found for AD or VaD. Simultaneous screening using rs11948613 and ApoE ε4 significantly improved the sensitivity of ApoE ε4 alone (from 0.40 to 0.75). CONCLUSION: SAR1B polymorphisms were associated with AD risk; results were not significant after correction for multiple tests. Simultaneous screening using SAR1B rs11948613 and ApoE ε4 status offered a better sensitivity for AD screening.