Background & Aims

Idiopathic chronic pancreatitis (ICP) is the second most common subtype of CP. In 1994, researchers reported the bimodal age at onset of ICP symptoms: early onset ICP (EO-ICP; median age, 19.2 y) and late-onset ICP (LO-ICP; median age, 56.2 y). Ages of onset and clinical features of ICP differed from those of alcohol-related CP (ACP). However, variants in PRSS1 had not yet been associated with ICP. We reexamined ages of onset of ICP in a large, North American cohort of patients, and investigated the effects of genetic factors and alcohol use in patients with EO-ICP, LO-ICP, and ACP.

Methods

We performed a cross-sectional analysis of patients with CP of European ancestry enrolled in the North American Pancreatitis Study 2, a prospective study of 1195 patients with CP from 26 centers in the United States from August 2000 through December 2014. We compared age at onset of symptoms for 130 patients with CP who were lifetime abstainers from alcohol (61 patients with early onset and 69 patients with late onset), 308 light to moderate alcohol drinkers with CP, and 225 patients with ACP and heavy to very heavy alcohol use. DNA from available patients was analyzed for variants associated with CP in SPINK1, CFTR, and CTRC. The Kruskal–Wallis test was used to compare continuous variables across groups and based on genetic variants.

Results

Median ages at onset of symptoms were 20 years for patients with EO-ICP and no alcohol use, 58 years for patients with LO-ICP and no alcohol use, 47 years for light to moderate alcohol drinkers with CP, and 44 years for patients with ACP. A higher proportion of patients with EO-ICP had constant pain (65%) than patients with LO-ICP (31%) (P = .04). A higher proportion of patients with ACP had pseudocysts (43%) than patients with EO-ICP (11%) (P = .001). A higher proportion of patients with EO-ICP had pathogenic variants in SPINK1, CFTR, or CTRC (49%) than patients with LO-ICP (23%), light to moderate alcohol drinking with CP (26%), or ACP (23%) (P = .001). Among patients with variants in SPINK1, those with EO-ICP had onset of symptoms at a median age of 12 years, and light to moderate alcohol drinkers with CP had an age at onset of 24 years. Among patients with variants in CFTR, light to moderate alcohol drinkers had an age at onset of symptoms of 41 years, but this variant did not affect age at onset of EO-ICP or ACP.

Conclusions

We confirmed previously reported ages at onset of symptoms for EO-ICP and LO-ICP in a North American cohort. We found differences in clinical features among patients with EO-ICP, LO-ICP, and ACP. Almost half of patients with EO-ICP have genetic variants associated with CP, compared with approximately one quarter of patients with LO-CP or ACP. Genetic variants affect ages at onset of symptoms in some groups.

中文翻译：

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北美队列中早期和迟发性特发性慢性胰腺炎患者出现症状时的年龄差异和遗传变异的影响。

背景与目标

特发性慢性胰腺炎 (ICP) 是 CP 的第二常见亚型。1994 年，研究人员报告了 ICP 症状发作的双峰年龄：早发 ICP（EO-ICP；中位年龄，19.2 岁）和晚发 ICP（LO-ICP；中位年龄，56.2 岁）。ICP的发病年龄和临床特征与酒精相关性CP（ACP）不同。然而，PRSS1中的变体尚未与 ICP 相关联。我们重新检查了北美大型患者队列中 ICP 的发病年龄，并调查了遗传因素和酒精使用对 EO-ICP、LO-ICP 和 ACP 患者的影响。

方法

我们对参加北美胰腺炎研究 2 的欧洲血统 CP 患者进行了横断面分析，该研究是一项前瞻性研究，从 2000 年 8 月到 2014 年 12 月，对来自美国 26 个中心的 1195 名 CP 患者进行了比较。我们比较了发病年龄130 名终生戒酒的 CP 患者（61 名早发患者和 69 名晚发患者）、308 名患有 CP 的轻度至中度饮酒者和 225 名患有 ACP 并重度至极重度饮酒的患者的症状。在SPINK1、CFTR和CTRC中分析了来自可用患者的 DNA 中与 CP 相关的变异。Kruskal-Wallis 检验用于比较跨组和基于遗传变异的连续变量。

结果

EO-ICP 且未饮酒的患者出现症状的中位年龄为 20 岁，LO-ICP 且未饮酒的患者为 58 岁，患有 CP 的轻度至中度饮酒者为 47 岁，患有 CP 的患者为 44 岁非加太。EO-ICP 患者持续疼痛的比例（65%）高于 LO-ICP 患者（31%）（P  = .04）。ACP 患者有假性囊肿的比例（43%）高于 EO-ICP 患者（11%）（P  = .001）。与LO -ICP (23%) 、轻度至中度饮酒伴 CP (26%) 或 ACP ( 23 %) (磷 = .001)。在SPINK1变异的患者中，EO-ICP 患者出现症状的中位年龄为 12 岁，患有 CP 的轻度至中度饮酒者的发病年龄为 24 岁。在CFTR变异的患者中，轻度至中度饮酒者出现症状的年龄为 41 岁，但这种变异不影响 EO-ICP 或 ACP 的发病年龄。

结论

我们在北美队列中证实了先前报道的 EO-ICP 和 LO-ICP 症状发作年龄。我们发现 EO-ICP、LO-ICP 和 ACP 患者的临床特征存在差异。几乎一半的 EO-ICP 患者具有与 CP 相关的基因变异，而大约四分之一的 LO-CP 或 ACP 患者。遗传变异会影响某些群体出现症状的年龄。