Effects of a major gene for apolipoprotein A-I concentration are thyroid hormone dependent in Mexican Americans

Apolipoprotein A-I (apoA-I) is the principal protein component of HDL cholesterol. The thyroid hormone triiodothryonine (T-3) 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 T-3 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 T-3 was allowed. The major gene appears not to be linked to the APOA1 structural locus. Genotypes differed significantly in their relationships to T-3 level. The AA and Aa genotypes showed a positive relationship with T-3 level, while the rarer aa homozygote showed a strong negative relationship with T-3. The relative variance in apoA-I concentration due to this major gene varied from 56% to 18%, depending on T-3 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.