I just posted this on the IfHI Member Forums, but I wanted to go ahead and post it here too to get a more broad range of responses. Enjoy!
I had a question today at our Individualist Society meeting here at SCNM that made me wonder if there's a connection between Type A's higher levels of serum cholesterol and their higher cortisol levels. The young lady wanted to know whether the higher levels of serum cholesterol in Type A's might simply be a response to the Type A's need for more cortisol to fuel their hyperreactive cortisol system. In other words, she was positing that a Type A's body might synthesize or release more cholesterol in response to the increased demand for cortisol, thus the increased levels of serum cholesterol in Type A.
I told her that I didn't think that was likely because the conversion of cholesterol to pregnenolone is the rate limiting step in steroid hormone production and therefore while more cortisol secretion might decrease the pregnenolone available for DHEA synthesis, it wouldn't affect serum cholesterol levels because there is already more than enough serum cholesterol in the vast majority of people, even those with clinically "low cholesterol" (like me), to provide for enough steroid synthesis to supply appropriate levels of cortisol. At the same time, I wasn't able to provide her with any mechanism that accounted for the increased levels of cortisol in Type A's.
We think that Type A's have more serum cholesterol, presumably because of a gene linkage with the Carboxyl ester lipase (CEL) gene located at the 9q34 locus (and therefore presumably linked with the ABO gene to some degree).1 The gene for CEL is known to exhibit a high frequency of polymorphism due to the presence of a hypervariable region in the 3'-end of the gene.2 Furthermore, association has been observed between polymorphism in the carboxyl ester lipase gene and serum cholesterol profile.3
Thus, with less intestinal breakdown of cholesterol esters, more intact absorption of cholesterol, and therefore more substrate to fuel steroid biosynthesis, is it plausible that the elevated levels of serum cholesterol in Type A are what is fueling the observed cortisol elevations? If not, is there some other, more plausible mechanism for the elevated levels of cortisol in Type A? I was unable to find reference to any gene coding for an enzyme more proximally involved in cortisol biosynthesis on the 9q34 locus in the current literature.
Any thoughts or ideas would be appreciated.
1.) Lidberg U, Nilsson J, Stromberg K, Stenman G, Sahlin P, Enerback S, Bjursell G. 1992. Genomic organization, sequence analysis, and chromosomal localization of the human carboxyl ester lipase (CEL) gene and a CEL-like (CELL) gene. Genomics. Jul;13(3): 630-40.
2.) Taylor, A. K., J. L. Zambaux, I. Klisak, T. Mohandas, R. S. Sparkes, M. C. Schotz, and A. J. Lusis. 1991. Carboxyl ester lipase: A highly polymorphic locus on human chromosome 9qter. Genomics. 10: 425–431.
3.) Bengtsson-Ellmark SH, Nilsson J, Orho-Melander M, Dahlenborg K, Groop L, Bjursell G. 2004. Association between a polymorphism in the carboxyl ester lipase gene and serum cholesterol profile. Eur J Hum Genet. Aug;12(