Tu1482 Common genetic susceptibility factors for recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) in white patients are rare in black patients

Aurora Affiliations

Aurora Health Care


Background: RAP and CP affects individuals of all demographics and geographic regions. Genetic factors increasing the susceptibility to pancreatitis in PRSS1, SPINK1, CFTR, and CTRC genes have been reported in many populations. Variations between people of European ancestry and populations from South or East Asia are known. Genetic testing for pancreatitis risks factors is now routinely performed in clinical practice, especially in patients with no obvious cause of pancreatitis. In the North American Pancreatitis Study (NAPS2), ~33% white CP patients were noted to have at least one, and ~10% had more than one variant in these genes. However there are no data on the prevalence of genetic mutations in black patients with pancreatitis. We tested the hypothesis that the genetic risk factors for pancreatitis are similar between black and white patients in the United States.

Methods: Controls (n= 253) and subjects with RAP (n=45) or CP (n=230), who identified themselves as AfricanAmerican, enrolled prospectively in the multicenter NAPS2 studies from 2000-2014 were studied. Demographic and phenotypic information was obtained from structured questionnaires completed by the study subjects and the enrolling physician. A blood sample was obtained from each subject, and peripheral blood leukocyte DNA was isolated and purified for analysis. Genotyping for known variants in pancreatitis risk genes PRSS1, SPINK1, CFTR and CTRC was performed by a combination of direct sequencing, restriction fragment length polymorphism (RFLP), multiplex SNP genotyping assays and individual taqman genotyping assays.

Results: Mean age of black controls, RAP and CP patients was 47.3±13.4, 45.7±13.6, and 51.9±10.6 years, and 38%, 38% and 63% of them were male, respectively. Physiciandefined alcohol etiology was present in 33% RAP and 77% CP patients. Of all the variants tested, only SPINK1 N34S was overrepresented in CP when compared with controls with borderline significance (CP 1.8%, controls 0%, p=0.051) (Table 1). Two CP patients had a CF mutation found to be specific for blacks with cystic fibrosis (3120+GtoA), one of whom was a compound heterozygote with a CF bicarbonate specific mutation (L967S) on the other allele. None of the pancreatitis patients had disease causing CTRC mutations. One CP patient was found to be carrying deleterious mutations in PRSS1 (R122H). Interestingly, 10/12 CP patients with CF mutations, and all 4 with SPINK1 mutation had physician-defined alcohol etiology.

Discussion: Prevalence of mutations in susceptibility genes reported in Caucasians is infrequent among black patients. Genetic sequencing of known susceptibility genes and regulatory elements, plus appropriately powered genetic association studies are needed to understand the risks and mechanisms of pancreatitis in black patients.

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