Locus on chromosome 6p linked to elevated HDL cholesterol serum levels and to protection against premature atherosclerosis in a kindred with familial hypercholesterolemia.
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.
Canizales-Quinteros
Samuel
S
Unidad de Biología Molecular y Medicina Genómica, Instituto de Investigaciones Biomédicas de la Universidad Nacional Autónoma de México, México City, Mexico.
Aguilar-Salinas
Carlos A
CA
Reyes-Rodríguez
Eduardo
E
Riba
Laura
L
Rodríguez-Torres
Maribel
M
Ramírez-Jiménez
Salvador
S
Huertas-Vázquez
Adriana
A
Fragoso-Ontiveros
Verónica
V
Zentella-Dehesa
Alejandro
A
Ventura-Gallegos
José L
JL
Vega-Hernández
Gerardo
G
López-Estrada
Angelina
A
Aurón-Gómez
Moisés
M
Gómez-Pérez
Francisco
F
Rull
Juan
J
Cox
Nancy J
NJ
Bell
Graeme I
GI
Tusié-Luna
Maria Teresa
MT
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
D008076:Cholesterol, HDL