title: Locus on chromosome 6p linked to elevated HDL cholesterol serum levels and to protection against premature atherosclerosis in a kindred with familial hypercholesterolemia.
abstract: Heterozygous familial hypercholesterolemia (FH) is a highly atherogenic genetic disorder leading to premature coronary heart disease (CHD), usually before 60 years of age. We studied an extended multigenerational kindred with FH linked to chromosome 1p32 in which atherosclerotic complications were either delayed or prevented in individuals with elevated HDL cholesterol (HDL-C) levels or hyperalphalipoproteinemia (HA). Premature CHD was observed in FH individuals without HA. The study of this family established that the HA trait in the family also followed an autosomal dominant mode of inheritance with a pattern of segregation independent from FH. We identified a locus on chromosome 6 linked to elevated HDL-C levels (HA) in this family. Haplotype analysis refined the localization to a 7.32-cM interval (73 to 80 cM from pter) flanked by markers D6S1280 and D6S1275. Parametric 2-point and multipoint analyses yielded maximum LOD scores of 3.05 and 3.17, respectively. This finding was confirmed with a nonparametric multipoint score of 3.78 (P=0.0009). We propose that this locus, linked to elevated HDL-C levels, confers protection against premature CHD within an FH context.
authors.affiliation: Unidad de Biología Molecular y Medicina Genómica, Instituto de Investigaciones Biomédicas de la Universidad Nacional Autónoma de México, México City, Mexico.
authors.forename: Samuel
authors.initials: S
authors.lastname: Canizales-Quinteros
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Aguilar-Salinas
authors.forename: Eduardo
authors.initials: E
authors.lastname: Reyes-Rodríguez
authors.forename: Laura
authors.initials: L
authors.lastname: Riba
authors.forename: Maribel
authors.initials: M
authors.lastname: Rodríguez-Torres
authors.forename: Salvador
authors.initials: S
authors.lastname: Ramírez-Jiménez
authors.forename: Adriana
authors.initials: A
authors.lastname: Huertas-Vázquez
authors.forename: Verónica
authors.initials: V
authors.lastname: Fragoso-Ontiveros
authors.forename: Alejandro
authors.initials: A
authors.lastname: Zentella-Dehesa
authors.forename: José L
authors.initials: JL
authors.lastname: Ventura-Gallegos
authors.forename: Gerardo
authors.initials: G
authors.lastname: Vega-Hernández
authors.forename: Angelina
authors.initials: A
authors.lastname: López-Estrada
authors.forename: Moisés
authors.initials: M
authors.lastname: Aurón-Gómez
authors.forename: Francisco
authors.initials: F
authors.lastname: Gómez-Pérez
authors.forename: Juan
authors.initials: J
authors.lastname: Rull
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Bell
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Tusié-Luna
mesh_terms: D000368:Aged; D008076:Cholesterol, HDL / Q000097:blood*; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000235:genetics*; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D006951:Hyperlipoproteinemias / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree
chemical_list: D008076:Cholesterol, HDL