We investigated the prevalence and characteristics of variants of five lipolysis-related genes in Korean patients with very high triglycerides (TGs). Twenty-six patients with TG levels >885 mg/dL were selected from 13545 Korean subjects. Five candidate genes, LPL, APOC2, GPIHBP1, APOA5, and LMF1, were sequenced by targeted next-generation sequencing. Predictions of functional effects were performed and matched against public databases of variants. Ten rare variants of three genes were found in nine (34.6%) patients (three in LPL, four in APOA5, and three in LMF1). Five were novel and all variants were suspected of being disease-caus-ing. Nine were heterozygous, and one (3.8%) had a homozygous rare variant of LPL. Six common variants of four genes were observed in 25 (96.2%) patients (one in LPL, one in GPIHBP1, two in APOA5, and two in LMF1). The c.G41T variant of GPIHBP1 and c.G533T variant of APOA5 were most frequent and found in 15 (57.7%) and 14 (53.8%) patients, respectively. Rare homozygous variants of the genes were very uncommon, while diverse rare heterozygous variants were commonly identified. Taken together, most study subjects may be manifesting the combined effects of rare heterozygous variants and common variants.
Bibliographical noteFunding Information:
This research was financially supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2012R1A4A1029061 and 2014R1A1A2056104) (SH Lee), the Bio & Medical Technology Development Program of the NRF funded by the Korean government, MSIP (2015M3A9B6029138) (SH Lee), the National Research Council of Science & Technology (NST) grant by the Korean government (MSIP) (No. CAP-12-2-KBSI) (SH Lee), and Basic Science Research Program through the NRF funded by the Ministry of Science, ICT and future Planning (No: NRF-2015R1A2A2A03 006577 (JH Lee), and a grant from Kyung Hee University in 2016 (KHU-20160543) (JH Lee).
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