Linkage Analysis of Plasma ApoE in Three Ethnic Groups: Multiple Genes with Context‐Dependent Effects

• Published in: Annals of human genetics Vol. 69; no. 2; pp. 157 - 167
• Main Authors: Klos, K. L. E., Kardia, S. L. R., Hixson, J. E., Turner, S. T., Hanis, C., Boerwinkle, E., Sing, C. F.
• Format: Journal Article
• Language: English
• Published: 9600 Garsington Road , Oxford OX4 2DQ , UK Blackwell Science Ltd 01-03-2005
• Subjects: APOE; apolipoprotein E; Apolipoproteins E - genetics; Chromosomes, Human, Pair 19; Ethnic Groups - genetics; Female; Genetic Linkage; Genome scan; Humans; Male; sample stratification
• ISSN: 0003-4800; 1469-1809
• DOI: 10.1046/j.1469-1809.2004.00148.x

Summary
We performed variance component‐based linkage analysis in four samples (two of non‐Hispanic European‐Americans from Rochester, MN; African‐Americans from Jackson, MS; and Mexican‐Americans from Starr County, TX) to identify chromosomal regions containing genes influencing plasma apolipoprotein E (apoE) levels. The APOE gene region on chromosome (chr) 19 was identified with a LOD ≥ 2.00 in both samples from Rochester and the sample from Jackson. Adjustment of apoE levels for differences among means of genotypes defined by the APOE ε2/3/4 alleles reduced evidence of linkage, indicating that the APOE gene was responsible for the majority of the linkage signal. In stratified linkage analyses, there was a LOD of 1.70 in the Starr County sibships with average total cholesterol (TC) above the median level for all sibships in that population. Adjustment for APOE genotype did not remove this LOD score, suggesting a second gene in this region may influence apoE variation. Evidence of linkage (LOD= 3.32) on chr 17 was observed in the Starr County sibships with average TC below the median. Inter‐individual variation in plasma apoE level may be influenced by variations in the structural gene, and at least one other gene whose effects differ among populations and are dependent on the influence of unmeasured genetic and environmental factors indexed by correlated measures of lipid metabolism.