Rare variants in TG-related genes were more frequent in severe hypertriglyceridemia than controls, and LPL gene variants were more frequent in those with acute pancreatitis (27.8% vs 4.7%).
Case-Control (n=149)
Does expanding genetic sequencing identify rare variants associated with severe hypertriglyceridemia and acute pancreatitis in Chinese patients?
Absolute Event Rate: 44.7% vs 26.1%
p-value: p=< 0.05
BACKGROUND: Severe hypertriglyceridemia (SHTG, TG ≥5·65 mmol/L), a disease, usually resulting from a combination of genetic and environmental factors, may increase the risk of acute pancreatitis (AP). However, previous genetic analysis has been limited by lacking of related observation of gene to AP. METHODS: The expanding genetic sequencing including 15 TG-related genes (LPL, LMF1, APOC2, GPIHBP1, GCKR, ANGPTL3, APOB, APOA1-A4-C3-A5, TRIB1, CETP, APOE, and LIPI) was performed within 103 patients who were diagnosed with primary SHTG and 46 age- and sex-matched normal controls. FINDINGS: Rare variants were found in 46 patients and 12 controls. The detection rate of rare variants in SHTG group increased by 19·5% via intensive genetic analysis. Presence of rare variants in LPL, APOA5, five LPL molecular regulating genes and all the sequenced genes were found to be associated with SHTG (p < 0·05). Of noted, patients with history of AP presented higher frequency of rare variants in LPL gene and all the LPL molecular regulating genes (27·8% vs.4·7% and 50·0% vs. 20·0%). The risk scores for SHTG determined by common TG-associated variants were increased in subgroups according to the extent of SHTG when they were compared with that of controls. Finally, patients without rare variants within SHTG group also presented higher risk scores than control group (p < 0·05). INTERPRETATION: Expanding genetic analysis had a higher detection rate of rare variants in patients with SHTG. Rare variants in LPL and its molecular regulating genes could increase the risk of AP among Chinese patients with SHTG. FUND: This work was partially supported by the Capital Health Development Fund (201614035) and CAMS. Major Collaborative Innovation Project (2016-I2M-1-011) awarded to Dr. Jian-Jun Li, MD, PhD.
Jin et al. (Fri,) conducted a case-control in Severe hypertriglyceridemia (SHTG) (n=149). Rare variants in TG-related genes vs. Absence of rare variants / normal controls was evaluated on Presence of rare variants in all sequenced genes in patients with SHTG versus normal controls (p=< 0.05). Rare variants in TG-related genes were more frequent in severe hypertriglyceridemia than controls, and LPL gene variants were more frequent in those with acute pancreatitis (27.8% vs 4.7%).