The presence of both pathogenic variants and a high polygenic risk score significantly increased the risk for acute pancreatitis compared to neither risk factor (OR 5.1; P=0.02).
Observational (n=363)
Yes
Does the presence of pathogenic variants and high polygenic risk scores predict the risk for very severe hypertriglyceridemia and acute pancreatitis in patients from lipid clinics?
The presence of both pathogenic variants and high polygenic risk scores significantly increases the risk for very severe hypertriglyceridemia and acute pancreatitis, suggesting a role for genetic testing in risk stratification.
Odds Ratio: 5.1
p-value: p=0.02
Background: Severe hypertriglyceridemia is often caused by variants in genes of triglyceride metabolism. These variants include rare, heterozygous pathogenic variants (PVs), or multiple common, small-effect single nucleotide polymorphisms that can be quantified using a polygenic risk score (PRS). The role of genetic testing to examine PVs and PRS in predicting risk for pancreatitis and severity of hypertriglyceridemia is unknown. Methods: We examined the relationship of PVs and PRSs associated with hypertriglyceridemia with the highest recorded plasma triglyceride level and risk for acute pancreatitis in 363 patients from 3 academic lipid clinics who underwent genetic testing (GBinsight’s Dyslipidemia Comprehensive Panel). Categories of hypertriglyceridemia included: normal triglyceride (<200 mg/dL), moderate (200–499 mg/dL), severe (500–999 mg/dL), or very severe (≥1000 mg/dL). Results: PVs and high PRSs were identified in 37 (10%) and 59 (16%) individuals, respectively. Patients with both had increased risk for very severe hypertriglyceridemia compared with those with neither genetic risk factor. Risk for acute pancreatitis was also increased in individuals with both genetic risk factors (odds ratio, 5.1 P =0.02 after controlling for age, race, sex, body mass index, and highest triglyceride level), but not in individuals with PV or high PRS alone. Conclusions: The presence of both PV and high PRS significantly increased risk for very severe hypertriglyceridemia and acute pancreatitis, whereas PV or PRS alone only modestly increased risk. Genetic testing may help identify patients with hypertriglyceridemia who have the greatest risk for developing pancreatitis and may derive the greatest benefit from novel triglyceride-lowering therapies.
Deshotels et al. (Thu,) conducted a observational in Hypertriglyceridemia (n=363). Presence of both pathogenic variants (PV) and high polygenic risk score (PRS) vs. Neither genetic risk factor was evaluated on Risk for acute pancreatitis (OR 5.1, p=0.02). The presence of both pathogenic variants and a high polygenic risk score significantly increased the risk for acute pancreatitis compared to neither risk factor (OR 5.1; P=0.02).
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