Restriction Isotyping of the Premature Termination Variant of Lipoprotein Lipase in Alberta Hutterites

Objective: Lipoprotein lipase (LPL) plays a pivotal role in lipoprotein metabolism. A relatively common LPL variant results from a C → G transversion in exon 9, which creates a premature termination codon (S447X) and results in a truncated LPL molecule lacking the C-terminal dipeptide Ser-Gly. We wished to determine the functional relevance of this variant. Design and Methods: We used MnII restriction digestion of amplified genomic DNA to genotype Alberta Hutterites for the S447X variant. We tested for association with biochemical phenotypes. Results: Complete linkage disequilibrium between alleles of an LPL genomic variant in intron 6 and LPL S447X was detected. However, as a single independent variable, LPL S447X genotype was not significantly associated with variation in any dependent biochemical variable in the Hutterites. Conclusions: Restriction isotyping for S447X permits large-scale screening of individuals to identify linkage relationships between this marker and other DNA variations of LPL and to study associations with clinical phenotypes