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

    Research output: Contribution to journalArticlepeer-review

    7 Scopus citations


    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 (APOAI). 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 APOAI 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.

    Original languageEnglish (US)
    Pages (from-to)1177-1183
    Number of pages7
    JournalArteriosclerosis, Thrombosis, and Vascular Biology
    Issue number9
    StatePublished - 1996


    • apolipoprotein A-I
    • genetics
    • linkage
    • lipoproteins
    • thyroid hormones

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine


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