No significant enrichment of rare functionally defective CPA1 variants in a large Chinese idiopathic chronic pancreatitis cohort

Hum Mutat. 2017 Aug;38(8):959-963. doi: 10.1002/humu.23254. Epub 2017 May 30.

Abstract

Rare functionally defective carboxypeptidase A1 (CPA1) variants have been reported to predispose to nonalcoholic chronic pancreatitis, mainly the idiopathic subtype. However, independent replication has so far been lacking, particularly in Asian cohorts where initial studies employed small sample sizes. Herein we performed targeted next-generation sequencing of the CPA1 gene in 1,112 Han Chinese idiopathic chronic pancreatitis (ICP) patients-the largest ICP cohort so far analyzed in a single population-and 1,580 controls. Sanger sequencing was used to validate called variants, and the CPA1 activity and secretion of all newly found variants were measured. A total of 18 rare CPA1 variants were characterized, 11 of which have not been previously described. However, no significant association was noted with ICP irrespective of whether all rare variants [20 out of 1,112 (1.8%) in patients vs. 24 out of 1,580 (1.52%) in controls; P = 0.57] or functionally impaired variants [three out of 1,112 (0.27%) in patients vs. two out of 1,580 (0.13%) in controls; P = 0.68] were considered.

Keywords: CPA1 gene; idiopathic chronic pancreatitis; missense mutations; next-generation sequencing; rare variants.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian Continental Ancestry Group
  • Carboxypeptidases A / genetics
  • Carboxypeptidases A / metabolism*
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Male
  • Mutation / genetics
  • Pancreatitis, Chronic / enzymology*
  • Pancreatitis, Chronic / genetics

Substances

  • Carboxypeptidases A