The Interaction Effect of 27‐Hydroxycholesterol Metabolism Disorder and CYP27A1 Single Nucleotide Polymorphisms in Mild Cognitive Impairment: Evidence from a Case–Control Study

Abstract

ScopeThe aim of the study is to investigate the relationship between 27‐hydroxycholesterol (27‐OHC), 27‐hydroxylase (CYP27A1) polymorphisms, and Alzheimer's disease (AD).Methods and resultsA case–control study based on EMCOA study includes 220 healthy cognition and mild cognitive impairment (MCI) subjects respectively, matched by sex, age, and education. The level of 27‐OHC and its related metabolites are examined by high performance liquid chromatography–mass spectrometry (HPLC−MS). The results show that 27‐OHC level is positively associated with risk of MCI (p < 0.001), negatively associated with specific domain of cognitive function. Serum 27‐OHC is positively associated with 7a‐hydroxy‐3‐oxo‐4‐cholestenoic acid (7‐HOCA) in cognitive healthy subjects, while positively associated with 3β‐hydroxy‐5‐cholestenoic acid (27‐CA) in MCI subjects (p < 0.001). CYP27A1 and Apolipoprotein E (ApoE) single nucleotide polymorphisms (SNPs) genotyping are determined. The global cognitive function is significant higher in Del‐carrier of rs10713583, compared with AA genotype (p = 0.007). Stroop Color‐Word Test Interference Trial (SCWT‐IT) is significant higher in G‐carrier genotype (p = 0.042), compared with TT genotype in rs12614206.ConclusionsThe results show that 27‐OHC metabolic disorder is associated with MCI and multi‐domain cognitive function. CYP27A1 SNPs is correlated to cognitive function, while the interaction between 27‐OHC and CYP27A1 SNPs need further study.