AUTHOR=Tremblay Karine , Dubois-Bouchard Camélia , Brisson Diane , Gaudet Daniel 

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

JOURNAL=Frontiers in Genetics

VOLUME=5

YEAR=2014

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2014.00090

DOI=10.3389/fgene.2014.00090

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Aim:</bold> To evaluate the association between genes regulating serine proteases, chymotrypsin C (<italic>CTRC</italic>) and serine peptidase inhibitor kazal type1 (<italic>SPINK1</italic>), 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.</p><p><bold>Method:</bold> The <italic>CTRC</italic> and <italic>SPINK1</italic> 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 <italic>CTRC</italic> and <italic>SPINK1</italic> 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.</p><p><bold>Results:</bold> Gene sequencing followed by genotype-stratified analyses of the <italic>CTRC</italic> and <italic>SPINK1</italic> genes in LPLD and controls revealed a positive association between recurrence of hospitalizations and the rs545634 (<italic>CTRC</italic>)—rs11319 (<italic>SPINK1</italic>) combination [<italic>OR</italic> = 41.4 (<italic>CI</italic>: 2.0–848.0); <italic>p</italic> = 0.016]. In all models, a positive family history of pancreatitis was a significant predictor of recurrent hospitalizations independently of the contribution of <italic>SPINK1</italic> or <italic>CTRC</italic> (<italic>p</italic> &lt; 0.001).</p><p><bold>Conclusion:</bold> 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.</p>