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P2‐064: Can the KIF6 polymorphism predict statin responsiveness in prodromal and symptomatic Alzheimer's disease?
Author(s) -
Sabbagh Marwan,
MalekAhmadi Michael,
Levenson Ian,
Sparks Larry
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.954
Subject(s) - medicine , statin , apolipoprotein e , homocysteine , genotype , disease , polymorphism (computer science) , cholesterol , endocrinology , gastroenterology , biology , genetics , gene
Background: 60% percent of studied populations for cardiovascular disease are carriers of the KIF6 gene variant (719Arg) that was found to substantially increase risk of coronary heart disease (CHD). Statin therapy was found to reduce riskofCHDevents incarriersof the (Arg/Arg,orTrp/Argpolymorphism) and carriers of these polymorphisms are more likely to respond to statin therapy. In this study, we describe the frequency of the KIF6 polymorphisms in a cohort of prodromal and symptomatic Alzheimer’s disease subjects Methods: 32 (12 prodromal AD, 20 symptomatic AD) cases from a memory disorders clinic were used for this study. Data from the advanced lipid panel were used to determine if group differences existed betweenKIF6 carriers and non-carriers. Analysis of covariance (ANCOVA)was used to determine group differences on lipid panel measures while accounting for the effects Apo E e4 carrier status and statin use. Advanced lipid panel measures included total cholesterol, all variants of low density lipoprotein (LDL) and high density lipoprotein (HDL), triglycerides, Apo B, ERLp(a), homocysteine, c-reactive protein. ApoE genotype and KIF6 polymorphism. Results: In this sample, 66% (n 1⁄4 21) had the Trp/Arg or Arg/Arg polymorphism of KIF6. Of the KIF6 carriers, 57% (n 1⁄4 12) were also Apo E e4 carriers. Of the 32 cases, 66% (n1⁄4 21) were taking a statin [c1⁄4 3.93 (df1⁄4 1), p1⁄4 .05]. For the entire sample, the mean total cholesterol for those taking statins was 182.43 (34.03) mg/dl while those not taking statins had a mean total cholesterol of 224.60 (53.79) mg/dl. Individuals who were KIF6 carriers had a mean total cholesterol of 206.57 (48.56) mg/dl while KIF6 non-carriers had a mean total cholesterol of 175.64 (26.82) mg/dl. After accounting for the effects of Apo E e4 carrier status and statin use, the only lipid panel variable to show a statistically significant difference between KIF6 carriers and non-carriers was HDL 3a percent [F 1⁄4 4.46, df (1.27), p 1⁄4 .04]. However, logistic regression analysis did not yield a significant effect for HDL 3a percent [OR 0.27 (0.07, 1.14) p1⁄4 .08] in terms of its association with KIF6. In addition, there was no significant association betweenApoE e4 carrier status andKIF6 carrier status [c1⁄4 0.13 (df1⁄4 1), p1⁄4 .72]Conclusions:The frequency of KIF6 carriers in this sample is somewhat higher than the general population (66% vs. 60%). This suggests that statin responsiveness in AD may depend on the presence of the KIF6 polymorphism. It is possible that a larger sample might express a distribution of carriers that is closer to that of the general population. The role that KIF6 plays in prodromal and clinical AD is unclear, however further investigation of this gene is warranted given the previously established associations of AD with cardiovascular conditions and events.