Detection of a major gene effect for LDL peak particle diameter and association with apolipoprotein H gene haplotype

Yohan Bossé, Mary F. Feitosa, Jean Pierre Després, Benoît Lamarche, Treva Rice, D. C. Rao, Claude Bouchard, Louis Pérusse, Marie Claude Vohl

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12 Scopus citations


Low-density lipoprotein (LDL) size, a coronary heart disease risk factor, is influenced by both genetic and environmental factors. Results from the Quebec Family Study (QFS) revealed that the LDL peak particle diameter (LDL-PPD) aggregates in families with a heritability coefficient above 50% and is affected by a major quantitative trait locus on chromosome 17q (LOD = 6.8). Complex segregation analyses have consistently demonstrated a major gene effect influencing LDL size. In the present study, we report a similar analysis in the QFS cohort, which suggests that a major gene explains 23% of the variance in age-body mass index and triglyceride-adjusted LDL-PPD. The most intuitive positional candidate gene on chromosome 17q is the apolipoprotein H gene. Direct sequencing of the promoter, coding regions, and exon-intron splicing boundaries of this gene revealed the presence of three missense mutations and two polymorphisms in the untranslated regions. Using family-based association tests, none of these variants was individually associated with LDL-PPD. However, analysis of the haplotypes constructed from the three missense mutations, suggested that one particular haplotype (frequency = 20.9%) was associated with a significant increase in LDL-PPD trait values (p = 0.046). Taken together, these results suggest the presence of a major gene effect influencing LDL-PPD and a positive association with a positional candidate gene located on chromosome 17q. Replication of the association between apolipoprotein H gene haplotype and LDL-PPD is required before reaching firm conclusion.

Original languageEnglish
Pages (from-to)231-239
Number of pages9
Issue number2
StatePublished - Oct 2005


  • Apolipoprotein H
  • Family-based association test
  • Haplotypes
  • LDL peak particle diameter
  • Segregation analysis


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