This study provides evidence that the minor allele of the LPL S774X variant is associated with larger VLDL diameters within groups defined by a lipoprotein diameter pattern which includes small LDL and HDL particles. The majority of individuals within these groups met ATP-III criteria for the MetS, and the pattern of large VLDL in addition to the small LDL and HDL particles additionally associates with higher IR, as well as the highest WC, fasting glucose and TGs, and diabetes prevalence. We did not find any association with lipoprotein diameter pattern and the D9N polymorphism.
The LPL S447X variant has been implicated in functional relevance to lipid parameters . The main functions of the LPL S447X variant are the hydrolysis of plasma TGs, and in mediating the clearance of atherogenic remnant lipoproteins from the circulation . Total missense, and nonsense mutations lead to type I hyperlipoproteinemia characterized by the accumulation of chylomicrons in the circulation . The validity of our findings is emphazied by previous associations of the S447X variant with a number of lipid parameters [6, 9, 10], and also the presence of the MetS , and associations with peak LDL particle size . However, this is the first study, to our knowledge, to associate variants with a pattern of particle sizes created using information from all three fractions of lipoprotein, which associates with the highest IR within the MetS.
The associations observed in this study must be viewed with a number of considerations. These include the small sample size combined with the low MAF for both variants, and the restriction of results to white Americans of European descent. It was this modest sample size that precluded gender stratified analyses. Nonetheless we provide evidence that the LPL 447X allele associates with a pattern of particle sizes (small LDL and HDL, and large VLDL diameters) which, in turn, is associated with the higher IR, WC, fasting TG and glucose and diabetes prevalence among groups where individuals meet ATP-III criteria for the MetS. Given the small sample size, and novelty of the phenotype (lipoprotein diameter pattern) replication in additional studies is warranted.