Single Nucleotide Polymorphism rs11136000 of CLU Gene (Clusterin, ApoJ) and the Risk of Late-Onset Alzheimer’s Disease in a Central European Population

Abstract

Clusterin (CLU; also known as apolipoprotein J, ApoJ) is a protein of inconstant structure known to be involved in diverse processes inside and outside of brain cells. CLU can act as a protein chaperon or protein solubilizer, lipid transporter as well as redox sensor and be anti- or proapoptotic, depending on context. Primary structure of CLU is encoded by CLU gene which contains single nucleotide polymorphisms (SNP's) associated with the risk of late-onset Alzheimer's disease (LOAD). Studying a sample of Czech population and using the case-control association approach we identified C allele of the SNP rs11136000 as conferring a reduced risk of LOAD, more so in females than in males. Additionally, data from two smaller subsets of the population sample suggested a possible association of rs11136000 with diabetes mellitus. In a parallel study, we found no association between rs11136000 and mild cognitive impairment (MCI). Our findings on rs11136000 and LOAD contradict those of some previous studies done elsewhere. We discuss the multiple roles of CLU in a broad range of molecular mechanisms that may contribute to the variability of genetic studies of CLU in various ethnic groups. The above discordance notwithstanding, our conclusions support the association of rs1113600 with the risk of LOAD.