title: Geographic distribution and genealogy of mutation 207 of the lipoprotein lipase gene in the French Canadian population of Québec.
abstract: Mutations in the lipoprotein lipase (LPL) gene, leading to partial or total inactivation of the enzyme, result in a hereditary clinical syndrome called familial LPL deficiency. The French Canadian population, which is primarily and historically located in the province of Québec, has the highest worldwide frequency of LPL-deficient patients. We have analyzed the prevalence, spatial distribution, and genealogy in the Québec population of a LPL gene mutation, M-207 (P207L in conventional notation), which changes the amino acid proline to leucine in position 207 of the LPL protein and inactivates the enzyme. Our results show that M-207 is the most prevalent LPL gene mutation among French Canadians and accounts for the largest proportion of LPL-deficient patients in this population. Genealogical reconstruction of French Canadian LPL-deficient patients point to 16 founders of M-207, all of whom migrated to Québec in the early seventeenth century from the north-western part of France, especially from the region of Perche. Most of the carriers of M-207 are, at present, found in Charlevoix, Saguenay-Lac-St-Jean regions of eastern Québec. On the basis of the number of homozygote M-207 LPL-deficient patients so far identified, we estimate that there are at least 31,000 carriers of this mutation in the province of Québec. This constitutes a large pool of individuals at risk for atherosclerosis and other lipid-related diseases, since LPL deficiency is considered to be a significant contributing factor in the etiology and development of these diseases.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Laval University, Ste-Foy, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Normand
authors.forename: J
authors.initials: J
authors.lastname: Bergeron
authors.forename: T
authors.initials: T
authors.lastname: Fernandez-Margallo
authors.forename: A
authors.initials: A
authors.lastname: Bharucha
authors.forename: M R
authors.initials: MR
authors.lastname: Ven Murthy
authors.forename: P
authors.initials: P
authors.lastname: Julien
authors.forename: C
authors.initials: C
authors.lastname: Gagné
authors.forename: C
authors.initials: C
authors.lastname: Dionne
authors.forename: M
authors.initials: M
authors.lastname: De Braekeleer
authors.forename: R
authors.initials: R
authors.lastname: Ma
mesh_terms: D000483:Alleles; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000208:ethnology / Q000235:genetics*; D015994:Incidence; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011792:Quebec
chemical_list: D008071:Lipoprotein Lipase