LINKAGE AND ASSOCIATION STUDIES OF THE LIPOPROTEIN LIPASE SER447TER MUTATION: THE HERITAGE FAMILY STUDY

39 The role of the Ser447Ter mutation in the lipoprotein lipase (LPL) gene on cardiorespiratory endurance, plasma triglycerides (TG) and body fat content remains to be elucidated. We have investigated the relationships between this mutation and selected phenotypes obtained before and after the 20-wk training program of the HERITAGE Family Study. Association studies were conducted on 82 sons and 85 daughters from 97 families of Caucasian descent. Phenotypes of interest were baseline levels and training changes in VO2max, post-heparin LPL activity, plasma total and VLDL-TG content, fat mass (FM) and% fat. The Ser447Ter mutation was determined using PCR-RFLP of the exon 9 and the Hinf I cutting site (allelic frequency = 0.10). In sons, no significant difference between genotypes was found for any of the phenotypes at baseline. However, the VO2max increase with training was significantly lower in carriers than non-carriers (12% vs 17%; p=0.03). Carriers had also a higher response to training for LPL activity than non-carriers (144% vs 46% respectively; p=0.01). In daughters, carriers had higher baseline plasma TG (p=0.02) and VLDL-TG content (p=0.009), FM (p=0.007) and%fat (p=0.02) compared to non-carriers. No significant effect of the mutation on changes with training was detected in daughters. Sib-pair (N=268) linkage analysis provided no evidence for linkage between the marker and any of the phenotypes. In conclusion, the Ser447Ter mutation in the LPL gene influences LPL activity and VO2max response to training in males and baseline TG levels and body fat content in females.