Geographic distribution and genealogy of mutation 207 of the lipoprotein lipase gene in the French Canadian population of Québec

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 Quebec, has the highest worldwide frequency of LPL-deficient patients. We have analyzed the prevalence, spatial distribution, and genealogy in the Quebec 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 Quebec 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 the Charlevoix, Saguenay-Lac-St-Jean regions of eastern Quebec. 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 Quebec. 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.