Upon joining the UT Southwestern faculty in the Center for Human Nutrition, the first project he undertook was to identify genetic polymorphism that is the basis for much of the variation in plasma lipoprotein levels in humans. At that time, the heritability of plasma lipoprotein levels had been clearly established, but little was known about which specific genes were responsible for variation in lipoprotein levels in the general population. Dr. Cohen instituted a program to better understand the genetic basis of abnormal lipoprotein levels. His initial studies confirmed that about 50% of the variability in HDL levels in the general population derive from genetic polymorphism. Moreover, through sibling-pair linkage analysis, he found that two genes--those encoding for hepatic lipase and apolipoprotein A1--account for 50% of the genetic variability. Dr. Cohen then focused his genetic studies on hepatic lipase, which seemed to be the most robust determinant of HDL levels. In follow-up studies on hepatic lipase he found that a polymorphism in the promoter region of the hepatic lipase gene that regulates the expression of this protein. He found through association studies that individuals who possess a common polymorphism in this region have elevated HDL levels. Subsequent studies with Center investigators proved that these individuals have a reduced expression of hepatic lipase.
