Genetic variants associated with triglyceride metabolism and fasting triglyceride concentrations: a systematic review and a meta-analysis

BACKGROUND AND OBJECTIVE: The genetic background of hypertriglyceridemia is complex. In this systematic review and meta-analysis, we determined genetic variants associated with fasting triglyceride (TG) and very-low-density lipoprotein-TG (VLDL-TG) concentrations in European adults. METHODS: We searched PubMed and the National Human Genome Research Institute-European Bioinformatics Institute (NHGRI-EBI) genome-wide association studies catalog for studies on genetic variants associated with fasting TG and VLDL-TG concentrations. We performed the meta-analysis on 23 variants from studies that met our criteria. A fixed-effects model was applied, with a random-effects model used when significant heterogeneity was detected. The Ensembl Variant Effect Predictor was used to annotate these variants. RESULTS: Overall, 157 studies were included, of which 130 were used for meta-analysis. Overall, 1837 variants were related to fasting TG and/or VLDL-TG (P ≤ .05). Our meta-analysis revealed 11 genetic variants associated with fasting TG: rs58542926 in the transmembrane 6 superfamily member 2 (TM6SF2) gene, rs738409 in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene, rs7903146 in the transcription factor 7-like 2 (TCF7L2) gene, rs320 and rs328 in the lipoprotein lipase (LPL) gene, and rs1801282 in the peroxisome proliferator-activated receptor γ2 (PPARγ2) gene were associated with lower TG concentrations, while rs693 in the apolipoprotein-B (APOB) gene, rs5128 in the apolipoprotein-c3 (APOC3) gene, rs662799 in the apolipoprotein A-V (APOA5) gene, rs662 in the paraoxonase 1 (PON1) gene, and rs1800588 in the hepatic lipase C (LIPC) gene were associated with higher TG concentrations. Five of those (rs58542926, rs738409, rs320, rs328, and rs1801282) were predicted to be deleterious to the protein function. CONCLUSION: This study identified variants associated with fasting TG and/or VLDL-TG concentrations in European adults, which may help in identifying genetically susceptible individuals and strengthening the accuracy of genetic risk prediction for TG-related outcomes.