RESTRICTION ISOTYPING OF THE PREMATURE TERMINATION VARIANT OF LIPOPROTEIN-LIPASE IN ALBERTA HUTTERITES

Objective: Lipoprotein lipase (LPL) plays a pivotal role in lipoprotei n metabolism. A relatively common LPL variant results from a C --> G t ransversion in exon 9, which creates a premature termination codon (S4 47X) and results in a truncated LPL molecule lacking the C-terminal di peptide Ser-Gly. We wished to determine the functional relevance of th is variant. Design and Methods: We used Mn/l restriction digestion of amplified genomic DNA to genotype Alberta Hutterites for the S447X var iant. We tested for association with biochemical phenotypes. Results: Complete linkage disequilibrium between alleles of an LPL genomic vari ant in intron 6 and LPL S447X was detected. However, as a single indep endent variable, LPL S447X genotype was not significantly associated w ith variation in any dependent biochemical variable in the Hutterites. Conclusions: Restriction isotyping for S447X permits large-scale scre ening of individuals to identify linkage relationships between this ma rker and other DNA variations of LPL and to study associations with cl inical phenotypes.