[Molecular genetics and lipoprotein lipase deficiency]

Lipoprotein lipase (LPL) deficiency is the main cause of familial chylomicronemia, a disease characterised by high fasting plasma triglyceride levels, that can be complicated with acute pancreatitis. This autosomal recessive disorder is rare (1/10(6) in the general population). Classically this disorder is non atherogenic, and the heterozygotes are asymptomatic. To date, 35 gene mutations have been described throughout the world. We have studied 12 families in which the molecular basis for LPL deficiency had been established (direct sequencing of PCR products) by the presence of mutations on the LPL gene, in the 18 homozygous probands. We have found 13 mutations: 7 missense mutations in exons 5 and 6, 3 deletions of few bases in exons 3 and 4, 1 insertion one base in exon 2, one large deletion of exon 9, and one partial duplication of exon 6. PCR and enzymatic restriction of the LPL gene were used as methods for screening mutations or analysing polymorphic markers. This allowed a discrimination between heterozygote carriers (C, n = 35) and non carriers (NC, n = 26). Both groups were comparable for age, sex ratio, body mass index, life style habits, and other risk factors for atherosclerosis. Comparison (U-test Mann Whitney) of plasma lipid values revealed a lower HDL cholesterol level (C: 0,47 +/- 0,11 g/l vs NC: 0,58 +/- 0,18 g/l, p < 0.05) and a higher triglyceride level (C: 1,15 +/- 0,73 g/l vs NC: 0,77 +/- 0,43 g/l, p < 0.05) in heterozygotes. Conversely to the homozygous state, heterozygous LPL deficiency predisposes to a lipid profile that may be atherogenic evenly frequent (approximately 1/500) in the general population.