Sequence analysis of the 5' region of the chymotrypsin C (CTRC) gene in chronic pancreatitis.

BACKGROUND/

OBJECTIVES

Loss-of-function chymotrypsin C (CTRC) variants increase the risk for chronic pancreatitis (CP) by reducing protective pancreatic CTRC activity. Variants in the 5' upstream region that includes the promoter might affect CTRC expression but have not been investigated to date. The aim of the present study was to address this knowledge gap.

METHODS

We analyzed ∼1.4 kb of the 5' region of the CTRC gene in 293 patients with chronic pancreatitis of alcoholic and non-alcoholic etiology and 402 controls from the Hungarian National Pancreas Registry by direct Sanger sequencing.

RESULTS

We identified 14 gene variants, which included 11 novel variants and 3 previously reported variants. When allele frequencies were considered, none of the variants were significantly overrepresented in CP cases or controls. Genotype distribution of the frequently occurring variant c.-913A>G showed a statistically significant enrichment of the homozygous GG genotype (versus the AA genotype) in CP cases versus controls (OR 1.67, 95 % CI 1.2-2.4, P 0.0053). However, the disease association was driven by the linkage disequilibrium with the known CTRC risk variant c.180C>T.

CONCLUSIONS

We found no significant association between variants in the 5' region of the CTRC gene and CP risk.