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.

journal_name

Circ Res

journal_title

Circulation research

authors

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,G

doi

10.1161/01.RES.0000064174.69165.66

subject

Has Abstract

pub_date

2003-03-21 00:00:00

pages

569-76

issue

5

eissn

0009-7330

issn

1524-4571

pii

01.RES.0000064174.69165.66

journal_volume

92

pub_type

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