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Molecular genetic evidence for a founder effect in familial hypercholesterolemia among French Canadians

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Summary

Familial hypercholesterolemia (FH), at a prevalence of about 1 in 200 in the French-Canadian population, is caused by a 10-kb deletion in the low-density lipoprotein (LDL) receptor gene in 60% of French-Canadian FH heterozygotes. We genotyped 159 FH patients who carry this common mutation and 221 healthy French-Canadian controls for five DNA restriction fragment length polymorphisms (RFLPs) of the LDL receptor gene. The allele numbers for four of the five RFLPs differed significantly (P < 0.001) between FH patients and control subjects. Our results suggest that the 10-kb deletion carrier allele is associated with a single haplotype (called the B haplotype). In a family study including a patient homozygous for the 10-kb deletion, we showed that the B haplotype cosegregates with the deletion in affected members and that the B haplotype is also associated with the normal allele in some members of the family. We identified 15 different haplotypes for the normal allele in 10-kb deletion carrier FH heterozygotes. These results offer strong support, at a molecular level, for the hypothesis of a founder effect for the 10-kb deletion in the French-Canadian population.

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Authors and Affiliations

  1. Clinical Research Institute of Montreal, affiliated with the University of Montreal, 110 Pine Avenue West, H2W 1R7, Montreal, Quebec, Canada

    Christine Bétard, M. Roy, A. Chamberland, S. Lussier-Cacan & J. Davignon

  2. Department of Biochemistry and Molecular Genetics, St. Mary's Hospital Medical School, Norfolk Place, W2 1PG, London, UK

    A. M. Kessling

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  1. Christine Bétard
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  2. A. M. Kessling
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  3. M. Roy
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  4. A. Chamberland
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  5. S. Lussier-Cacan
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  6. J. Davignon
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Bétard, C., Kessling, A.M., Roy, M. et al. Molecular genetic evidence for a founder effect in familial hypercholesterolemia among French Canadians. Hum Genet 88, 529–536 (1992). https://doi.org/10.1007/BF00219339

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