Common Genetic Variants Contribute to Primary Hypertriglyceridemia without Differences between Familial Combined Hyperlipidemia and Isolated Hypertriglyceridemia
Background—The majority of hypertriglyceridemias (HTG) are diagnosed as familial combined hyperlipidemia (FCHL) and primary isolated HTG. The contribution of common genetic variants in primary HTG and the genetic difference between FCHL and isolated HTG have not been thoroughly examined.
Methods and Results—This study involved 580 patients with HTG and 403 controls. Of the 37 single nucleotide polymorphisms (SNPs) examined, 12 located in 10 genes showed allelic and/or genotype frequency differences between HTG and controls. The minor alleles of APOE, APOA5, GALNTN2 and GCKR variants were positively correlated with plasma triglycerides while minor alleles of ADIPOR2, ANGPTL3, LPL and TRIB1 polymorphisms were inversely associated. Body mass index, glucose, sex, rs328 and rs7007797 in LPL, rs662799 and rs3135506 in APOA5, as well as and rs1260326 in GCKR explained 36% of the variability in plasma triglycerides, 7.3% of which was attributable to the genetic variables. LPL, GCKR, and APOA5 polymorphisms fit dominant, recessive, and additive inheritance models, respectively. Variants more frequently identified in isolated HTG were rs7412 in APOE and rs1800795 in IL6; rs2808607 in CYP7A1 and rs3812316 and rs17145738 in MLXIPL were more frequent in FCHL. The other 32 SNPs presented similar frequencies between isolated HTG and FCHL.
Conclusions—Common genetic variants found in LPL, APOA5 and GCKR are associated with triglycerides levels in patients with primary HTG. FCHL and isolated HTG are probably trace to an accumulation of genetic variants predisposing to familial and sporadic HTG, or to HTG and hypercholesterolemia in case of FCHL.
- Received November 12, 2013.
- Revision received June 19, 2014.
- Accepted July 8, 2014.