Clusterin variants extend links between Alzheimer disease and blood lipids

A recent report in the American Journal of Clinical Nutrition shows that genetic variation in the gene encoding clusterin (CLU or APOJ) showed strong and significant association with plasma fatty acids in an Alaskan Eskimo population. This is relevant to liver function, heart disease and Alzheimer disease (AD). In fact, other characteristics of CLU serve to strengthen the links between AD and blood lipids in a manner similar to APOE (apolipoprotein E).

There are in excess of 100 scientific publications describing different aspects of CLU gene and protein function. Those are not easily summarized here but can be accessed here. Briefly, the protein has no known function and seems to be involved in several basic biological events such as cell death, tumor progression, and neurodegenerative disorders (provided by RefSeq).

I have collected some interesting data on CLU:

Two separate GWAS have shown an association with Alzheimer disease. These are papers by Harold, et al. (2009) and Lambert, et al. (2009) in populations in Europe or of European ancestry. Otowa, et al (2009) showed also by GWAS an association to panic disorder in a Japanese population.

According to SymAtlas, this gene is very highly expressed in human liver.

Our preliminary analysis indicates that CLU is under positive selection in the human lineage (based on amino acid substitution rates). This could indicate responsiveness to some character of the environment. Diet perhaps?

Proteomic analysis of aortas of Apoe -/- mice showed a large increase in Clu protein expression (Wu, Tan, et al. (2007) J. Proteome Res. 6:4728).

Lastly and perhaps most interestingly, CLU is differentially expressed in human individuals with low vs high response to caloric restriction in terms of weight loss (Bouchard Vohl 2010 Am J Clin Nutr 91:309).