Evidence of linkage of familial hypoalphalipoproteinemia to a novel locus on chromosome 11q23

Coronary heart disease (CHD) accounts for half of the 1 million deaths annu ally ascribed to cardiovascular disease and for almost all of the 1.5 milli on acute myocardial infarctions. Within families affected by early and appa rently heritable CHD, dyslipidemias have a much higher prevalence than in t he general population; 20%-30% of early familial CHD has been ascribed to p rimary hypoalphalipoproteinemia (low HDL-C). This study assesses the eviden ce for linkage of low HDL-C to chromosomal region 11q23 in 105 large Utah p edigrees ascertained with closely related clusters of early CHD and expande d on the basis of dyslipidemia. Linkage analysis was performed by use of 22 STRP markers in a 55-cM region of chromosome 11. Two-point analysis based on a general, dominant-phenotype model yielded LODs of 2.9 for full pedigre es and 3.5 for 167 four-generation split pedigrees. To define a localizatio n region, model optimization was performed using the heterogeneity, multipo int LOD score (mpHLOD). This linkage defines a region on 11q23.3 that is si milar to 10 cM distal to-and apparently distinct from-the ApoAI/CIII/AlV ge ne cluster and thus represents a putative novel localization for the low HD L-C phenotype.