title: Model-fitting and linkage analysis of sodium-lithium countertransport.
abstract: 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.
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA. sandy@genetics.utah.edu
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Hasstedt
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Camp
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hopkins
authors.forename: Hilary
authors.initials: H
authors.lastname: Coon
authors.forename: Jason T
authors.initials: JT
authors.lastname: McKinney
authors.forename: Richard M
authors.initials: RM
authors.lastname: Cawthon
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hunt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017920:Antiporters / Q000235:genetics* / Q000378:metabolism; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D016013:Likelihood Functions; D008094:Lithium / Q000378:metabolism*; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D012964:Sodium / Q000378:metabolism*
chemical_list: D017920:Antiporters; C045885:sodium-lithium countertransporter; D008094:Lithium; D012964:Sodium