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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:1177-1183.)
© 1996 American Heart Association, Inc.

Articles

Effects of a Major Gene for Apolipoprotein A-I Concentration Are Thyroid Hormone Dependent in Mexican Americans

John Blangero; Sarah Williams-Blangero; Michael C. Mahaney; Anthony G. Comuzzie; James E. Hixson; Paul B. Samollow; R. Mark Sharp; Michael P. Stern; Jean W. MacCluer

the Department of Genetics, Southwest Foundation for Biomedical Research (J.B., S.W.-B., M.C.M., A.G.C., J.E.H., P.B.S., R.M.S., J.W.M.), and the Division of Clinical Epidemiology, Department of Medicine, University of Texas Health Science Center (M.P.S.), San Antonio, Tex.

Correspondence to John Blangero, Department of Genetics, Southwest Foundation for Biomedical Research, 7620 NW Loop 410, San Antonio, TX 78227. E-mail john@darwin.sfbr.org.

Apolipoprotein A-I (apoA-I) is the principal protein component of HDL cholesterol. The thyroid hormone triiodothryonine (T₃) is known to be a potent mediator of expression of the apoA-I structural gene (APOA1). Using complex segregation analysis, we detected a major gene influencing plasma concentration of apoA-I and examined its interaction with T₃ serum level in Mexican Americans participating in the San Antonio Family Heart Study. Strong evidence for a major locus with two alleles (A and a) determining apoA-I level was obtained when interaction with T₃ was allowed. The major gene appears not to be linked to the APOA1 structural locus. Genotypes differed significantly in their relationships to T₃ level. The AA and Aa genotypes showed a positive relationship with T₃ level, while the rarer aa homozygote showed a strong negative relationship with T₃. The relative variance in apoA-I concentration due to this major gene varied from 56% to 18%, depending on T₃ level. On average, the major gene accounts for 30% of apoA-I variation, and shared-household effects account for an additional 11%. These findings suggest that thyroid hormone has an important role in the genetic control of lipoprotein metabolism.

Key Words: apolipoprotein A-I • lipoproteins • thyroid hormones • genetics • linkage

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