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 association between serum cholesterol levels and the HTTLPR insertion/deletion polymorphism of the promoter region of the serotonin transporter gene (HTT, SLC6A4). As a follow-up we examined the potential association of this polymorphism with cholesterol and triglyceride levels, or heart disease, in two other groups of subjects. We examined the possible association between cholesterol levels and heart disease and genotypes of the HTTLPR insertion/deletion polymorphism of the promoter region of the HTT gene, in three independent 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 in the LS heterozygotes than either LL or SS homozygotes, indicating a heterosis effect (P </= 0.0001). This was replicated in Group 2 (P </= 0.015). Triglyceride levels were also significantly elevated in the LS subjects (P </= 0.001). In Groups 1 and 3 there was a significant association between LS heterozygosity and heart 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 disease. Replication of these findings in independent, epidemiologically based studies is required.
Comings
D E
DE
Department of Medical Genetics, City of Hope National Medical Center, Duarte, California, 91910, USA. dcomings@mindspring.com
MacMurray
J P
JP
Gonzalez
N
N
Ferry
L
L
Peters
W R
WR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood*; D003327:Coronary Disease / Q000453:epidemiology* / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins; D013177:Sports; D014280:Triglycerides / Q000097:blood
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D014280:Triglycerides; D002784:Cholesterol