Original Research ARTICLE

Front. Genet., 22 April 2014 |

Association of CTRC and SPINK1 gene variants with recurrent hospitalizations for pancreatitis or acute abdominal pain in lipoprotein lipase deficiency

  • 1Department of Medicine, Université de Montréal, Montreal, Canada
  • 2ECOGENE-21 Clinical Research Center, Saguenay, QC, Canada

Background: 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.

Aim: 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.

Method: 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.

Results: 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).

Conclusion: 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.

Keywords: severe hypertriglyceridemia, lipoprotein lipase deficiency (LPLD), pancreatitis, CTRC gene, SPINK1 gene, LPL gene

Citation: Tremblay K, Dubois-Bouchard C, Brisson D and Gaudet D (2014) Association of CTRC and SPINK1 gene variants with recurrent hospitalizations for pancreatitis or acute abdominal pain in lipoprotein lipase deficiency. Front. Genet. 5:90. doi: 10.3389/fgene.2014.00090

Received: 12 February 2014; Accepted: 02 April 2014;
Published online: 22 April 2014.

Edited by:

M. Z. A. Bhuiyan, University Hospital Lausanne (CHUV), Switzerland

Reviewed by:

Bruna De Felice, University of Naples II, Italy
Xusheng Wang, St. Jude Children's Research Hospital, USA

Copyright © 2014 Tremblay, Dubois-Bouchard, Brisson and Gaudet. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Daniel Gaudet, Department of Medicine, ECOGENE-21 Research Center, Université de Montréal, Pavillon des Augustines, 5th floor, 305 St-Vallier street, Chicoutimi, QC G7H 5H6, Canada e-mail:

These authors have contributed equally to this work.