Model-fitting and linkage analysis of sodium-lithium countertransport
Increased sodium-lithium countertransport activity (SLC) associates with hypertension and is highly heritable, yet the underlying genes remain unknown. SLC, measured on 1113 and remeasured 2-3 years later on 675 adult members of 48 Utah pedigrees, was tested for candidate gene association, major locus inheritance, and linkage to genome scan markers using a bivariate model with genotype-specific effects of age, body mass index (BMI), and triglycerides level (TG). No effect of the alpha-adducin Gly460Trp polymorphism on SLC was found. In contrast, SLC increased with age in carriers of apolipoproteinE varepsilon2 (85 individuals; 8.7% of the sample) and decreased in noncarriers. Model-fitting analyses inferred two additional loci with genotype-specific responses to BMI and TG. Using the inferred model, lod scores >2 were obtained for D3S3038, D11S4464, and D10S677 for the BMI-responsive locus, and for D8S1048 for the TG-responsive locus.