Association of the serotonin transporter gene with serum cholesterol levels and heart disease

In a study of a group of elderly athletes we observed an unexpected associa tion between serum cholesterol levels and the HTTLPR insertion/deletion pol ymorphism of the promoter region of the serotonin transporter gene (HTT, SL C6A4). As a follow-up we examined the potential association of this polymor phism with cholesterol and triglyceride levels, or heart disease, in two ot her groups of subjects. We examined the possible association between choles terol levels and heart disease and genotypes of the HTTLPR insertion/deleti on polymorphism of the promoter region of the HTT gene, in three independen t study populations ranging from 42 to 90 years of age. For subjects 55 to 70 years of age in Group 1, cholesterol levels were significantly greater i n the LS heterozygotes than either LL or SS homozygotes, indicating a heter osis effect (P less than or equal to 0.0001). This was replicated in Group 2 (P less than or equal to 0.015). Triglyceride levels were also significan tly elevated in the LS subjects (P less than or equal to 0.001). In Groups 1 and 3 there was a significant association between LS heterozygosity and h eart disease, angina, and heart attacks in subjects 70 years of age or less . All of these associations were absent in subjects >70 years of age. While these studies are preliminary and exploratory, they are consistent with a relationship of the HTT gene in cholesterol levels and a risk for heart dis ease. Replication of these findings in independent, epidemiologically based studies is required. (C) 1999 Academic Press.