Guay Simon-Pierre, Gagnon Eloi, Paquette Martine, Thériault Sébastien, Arsenault Benoit J, Baass Alexis
Genetic Dyslipidemia Clinic, Montreal Clinical Research Institute, Montreal, Quebec, Canada.
Division of Endocrinology, Department of Medicine, Université de Montréal, Montreal, Quebec, Canada.
J Gastroenterol Hepatol. 2024 Dec;39(12):2639-2644. doi: 10.1111/jgh.16759. Epub 2024 Oct 10.
Acute pancreatitis (AP) is a complex disease most commonly caused by gallstones, alcohol intake, or hypertriglyceridemia. Even in subjects with hypertriglyceridemia, the risk of AP is heterogeneous. Identifying individuals with a high genetic susceptibility to AP could contribute to a better risk stratification in the clinic. This study aimed to determine if a weighted polygenic risk score (PRS) of common variants in pancreatitis susceptibility genes can independently predict all-cause AP incidence in the general population.
A weighted PRS was calculated for 484 932 individuals from the UK Biobank, including 3346 individuals who developed AP during follow-up. The PRS included eight single nucleotide polymorphisms in known pancreatitis susceptibility genes.
Individuals with a pancreatitis PRS above the 90th percentile had a 1.21-fold (1.03-1.43; P = 0.02) increased risk of AP compared with those with a pancreatitis PRS below the 90th percentile. When comparing individuals in the third tertile versus the first tertile, the risk of AP was 1.13-fold (1.00-1.28; P = 0.06) higher. Individuals with both a high triglyceride (TG) level and a high pancreatitis PRS (third tertile) had a 2.31-fold (1.83-2.93; P = 3.4 × 10) increased risk of AP compared with those with a low pancreatitis PRS and a low TG level (first tertile). Overall, the association between pancreatitis PRS and incident AP was independent of baseline TG level.
Results of this study suggest that the accumulation of common variants in pancreatitis susceptibility genes is associated with all-cause AP incidence. Pancreatitis PRS could help clinicians identify patients who may be at higher risk of AP and who may benefit from more aggressive treatment.
急性胰腺炎（AP）是一种复杂疾病，最常见的病因是胆结石、饮酒或高甘油三酯血症。即使在高甘油三酯血症患者中，AP的风险也存在异质性。识别对AP具有高遗传易感性的个体有助于在临床上进行更好的风险分层。本研究旨在确定胰腺炎易感性基因中常见变异的加权多基因风险评分（PRS）是否能独立预测普通人群中全因AP的发病率。
为英国生物银行的484932名个体计算加权PRS，其中包括3346名在随访期间发生AP的个体。该PRS包括已知胰腺炎易感性基因中的8个单核苷酸多态性。
胰腺炎PRS高于第90百分位数的个体发生AP的风险比PRS低于第90百分位数的个体高1.21倍（1.03 - 1.43；P = 0.02）。比较处于第三三分位数与第一三分位数的个体时，AP风险高1.13倍（1.00 - 1.28；P = 0.06）。高甘油三酯（TG）水平且胰腺炎PRS高（第三三分位数）的个体发生AP的风险比胰腺炎PRS低且TG水平低（第一三分位数）的个体高2.31倍（1.83 - 2.93；P = 3.4×10）。总体而言，胰腺炎PRS与AP发病之间的关联独立于基线TG水平。
本研究结果表明，胰腺炎易感性基因中常见变异的积累与全因AP发病率相关。胰腺炎PRS可帮助临床医生识别可能发生AP风险较高且可能从更积极治疗中获益的患者。
