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.
journal_name
Circ Resjournal_title
Circulation researchauthors
Canizales-Quinteros S,Aguilar-Salinas CA,Reyes-Rodríguez E,Riba L,Rodríguez-Torres M,Ramírez-Jiménez S,Huertas-Vázquez A,Fragoso-Ontiveros V,Zentella-Dehesa A,Ventura-Gallegos JL,Vega-Hernández G,López-Estrada A,Aurón-Gómez M,Gdoi
10.1161/01.RES.0000064174.69165.66subject
Has Abstractpub_date
2003-03-21 00:00:00pages
569-76issue
5eissn
0009-7330issn
1524-4571pii
01.RES.0000064174.69165.66journal_volume
92pub_type
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