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

Abstract

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.