Department of Medicine, Université de Montréal Montreal, Canada ; ECOGENE-21 Clinical Research Center Saguenay, QC, Canada.
Front Genet. 2014 Apr 22;5:90. doi: 10.3389/fgene.2014.00090. eCollection 2014.
There are important inter-individual variations in the incidence and severity of acute pancreatitis in patients with severe hypertriglyceridemia. Several genes involved in triglyceride-rich lipoprotein metabolism or serine proteases pathways are known to influence the risk of pancreatitis.
To evaluate the association between genes regulating serine proteases, chymotrypsin C (CTRC) and serine peptidase inhibitor kazal type1 (SPINK1), and recurrence of hospitalizations for acute pancreatitis or severe abdominal pain in patients with Lipoprotein Lipase Deficiency (LPLD), a rare and extreme monogenic model of severe hypertriglyceridemia and pancreatitis.
The CTRC and SPINK1 genes promoter and coding regions sequencing has been performed in a sample of 38 LPLD adults (22 men and 16 women) and 100 controls (53 men and 47 women). Estimation of the association of CTRC and SPINK1 gene variants or combinations of variants with history of hospitalizations for pancreatitis or acute abdominal pain in LPLD was investigated using non-parametric analyses with correction for multiple testing and logistic regression models controlling for age, gender, family history, and life habits.
Gene sequencing followed by genotype-stratified analyses of the CTRC and SPINK1 genes in LPLD and controls revealed a positive association between recurrence of hospitalizations and the rs545634 (CTRC)-rs11319 (SPINK1) combination [OR = 41.4 (CI: 2.0-848.0); p = 0.016]. In all models, a positive family history of pancreatitis was a significant predictor of recurrent hospitalizations independently of the contribution of SPINK1 or CTRC (p < 0.001).
These results suggest that a positive family history of pancreatitis and genetic markers in the serine protease pathways could be associated with a risk of recurrent hospitalization for acute pancreatitis in severe hypertriglyceridemia due to LPLD.
在严重高甘油三酯血症患者中，急性胰腺炎的发病率和严重程度存在重要的个体间差异。已知参与甘油三酯丰富的脂蛋白代谢或丝氨酸蛋白酶途径的几个基因会影响胰腺炎的风险。
评估调节丝氨酸蛋白酶的基因——糜蛋白酶 C（CTRC）和丝氨酸肽酶抑制剂 kazal 型 1（SPINK1）与脂蛋白脂肪酶缺乏症（LPLD）患者因急性胰腺炎或严重腹痛再次住院之间的关联，LPLD 是一种罕见的严重高甘油三酯血症和胰腺炎的极端单基因模型。
对 38 名 LPLD 成年患者（22 名男性和 16 名女性）和 100 名对照者（53 名男性和 47 名女性）的 CTRC 和 SPINK1 基因启动子和编码区进行了测序。使用非参数分析和逻辑回归模型，校正了年龄、性别、家族史和生活习惯等因素，对 CTRC 和 SPINK1 基因变异或变异组合与 LPLD 患者因胰腺炎或急性腹痛再次住院的相关性进行了评估。
对 LPLD 和对照组的 CTRC 和 SPINK1 基因进行测序，并对基因型进行分层分析，结果显示，再次住院与 rs545634（CTRC）-rs11319（SPINK1）组合呈正相关[比值比（OR）=41.4（95%置信区间：2.0-848.0）；p=0.016]。在所有模型中，胰腺炎家族史阳性是再次住院的独立预测因素，独立于 SPINK1 或 CTRC 的作用（p<0.001）。
这些结果表明，严重高甘油三酯血症的 LPLD 患者中，胰腺炎阳性家族史和丝氨酸蛋白酶途径的遗传标志物可能与急性胰腺炎再次住院的风险相关。
