Anna Evans Phillips1, Jessica LaRusch2, Phil Greer1, Judah Abberbock3, Samer Alkaade4, Stephen T Amann5, Michelle A Anderson6, John Baillie7, Peter A Banks8, Randall E Brand1, Darwin Conwell9, Gregory A Coté10, Christopher E Forsmark11, Timothy B Gardner12, Andres Gelrud13, Nalini Guda14, Michele Lewis15, Mary E Money16, Thiruvengadam Muniraj17, Bimaljit S Sandhu18, Stuart Sherman19, Vikesh K Singh20, Adam Slivka1, Gong Tang3, C Mel Wilcox21, David C Whitcomb22, Dhiraj Yadav23. 1. Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States. 2. Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States; Ariel Precision Medicine, Pittsburgh PA, United States. 3. Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States. 4. Department of Medicine, Saint Louis University, St. Louis, MO, United States. 5. Digestive Health Specialists, Tupelo, MS, United States. 6. Department of Medicine, University of Michigan, Ann Arbor, MI, United States. 7. Department of Medicine, Virginia Commonwealth University, Richmond, VA, United States. 8. Department of Medicine, Brigham and Women's Hospital, Boston, MA, United States. 9. Department of Medicine, Ohio State University, Columbus, OH, United States. 10. Department of Medicine, Medical University of South Carolina, Charleston, SC, United States. 11. Department of Medicine, University of Florida, Gainesville, FL, United States. 12. Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, United States. 13. Department of Medicine, University of Chicago, Chicago, IL, United States. 14. GI Associates LLC, Aurora Health Care, St. Luke's Medical Center, Milwaukee, WI, United States. 15. Department of Medicine, Mayo Clinic, Jacksonville, FL, United States. 16. Washington County Hospital, Hagerstown, MD, United States. 17. Department of Medicine, Griffin Hospital, Yale Affiliate, New Haven, CT, United States. 18. Richmond Gastroenterology Associates, St. Mary's Hospital, Richmond, VA, United States. 19. Department of Medicine, Indiana University, Indianapolis, IN, United States. 20. Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, United States. 21. Department of Medicine, University of Alabama Birmingham, Birmingham, AL, United States. 22. Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States; Department of Cell Biology & Physiology, University of Pittsburgh, Pittsburgh, PA, United States; Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, United States. 23. Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States. Electronic address: yadavd@upmc.edu.
Abstract
BACKGROUND: Multiple pathogenic genetic variants are associated with pancreatitis in patients of European (EA) and Asian ancestries, but studies on patients of African ancestry (AA) are lacking. We evaluated the prevalence of known genetic variations in African-American subjects in the US. METHODS: We studied prospectively enrolled controls (n = 238) and patients with chronic (CP) (n = 232) or recurrent acute pancreatitis (RAP) (n = 45) in the NAPS2 studies from 2000-2014 of self-identified AA. Demographic and phenotypic information was obtained from structured questionnaires. Ancestry and admixture were evaluated by principal component analysis (PCA). Genotyping was performed for pathogenic genetic variants in PRSS1, SPINK1, CFTR and CTRC. Prevalence of disease-associated variants in NAPS2 subjects of AA and EA was compared. RESULTS: When compared with CP subjects of EA (n = 862), prevalence of established pathogenic genetic variants was infrequent in AA patients with CP, overall (29 vs. 8.19%, OR 4.60, 95% CI 2.74-7.74, p < 0.001), and after stratification by alcohol etiology (p < 0.001). On PCA, AA cases were more heterogeneous but distinct from EA subjects; no difference was observed between AA subjects with and without CP-associated variants. Of 19 A A patients with CP who had pathogenic genetic variants, 2 had variants in PRSS1 (R122H, R122C), 4 in SPINK1 (all N34S heterozygotes), 12 in CFTR (2 CFTRsev, 9 CFTRBD, 1 compound heterozygote with CFTRsev and CFTRBD), and 1 in CTRC (R254W). CONCLUSION: Pathogenic genetic variants reported in EA patients are significantly less common in AA patients. Further studies are needed to determine the complex risk factors for AA subjects with pancreatitis.
BACKGROUND: Multiple pathogenic genetic variants are associated with pancreatitis in patients of European (EA) and Asian ancestries, but studies on patients of African ancestry (AA) are lacking. We evaluated the prevalence of known genetic variations in African-American subjects in the US. METHODS: We studied prospectively enrolled controls (n = 238) and patients with chronic (CP) (n = 232) or recurrent acute pancreatitis (RAP) (n = 45) in the NAPS2 studies from 2000-2014 of self-identified AA. Demographic and phenotypic information was obtained from structured questionnaires. Ancestry and admixture were evaluated by principal component analysis (PCA). Genotyping was performed for pathogenic genetic variants in PRSS1, SPINK1, CFTR and CTRC. Prevalence of disease-associated variants in NAPS2 subjects of AA and EA was compared. RESULTS: When compared with CP subjects of EA (n = 862), prevalence of established pathogenic genetic variants was infrequent in AA patients with CP, overall (29 vs. 8.19%, OR 4.60, 95% CI 2.74-7.74, p < 0.001), and after stratification by alcohol etiology (p < 0.001). On PCA, AA cases were more heterogeneous but distinct from EA subjects; no difference was observed between AA subjects with and without CP-associated variants. Of 19 A A patients with CP who had pathogenic genetic variants, 2 had variants in PRSS1 (R122H, R122C), 4 in SPINK1 (all N34S heterozygotes), 12 in CFTR (2 CFTRsev, 9 CFTRBD, 1 compound heterozygote with CFTRsev and CFTRBD), and 1 in CTRC (R254W). CONCLUSION: Pathogenic genetic variants reported in EA patients are significantly less common in AA patients. Further studies are needed to determine the complex risk factors for AA subjects with pancreatitis.
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