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A loss-of-function p.G191R variant in the anionic trypsinogen (PRSS2) gene in Japanese patients with pancreatic disorders
  1. Kiyoshi Kume (kkume{at}int3.med.tohoku.ac.jp)
  1. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
    1. Atsushi Masamune
    1. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
      1. Yasuhiko Takagi
      1. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
        1. Kazuhiro Kikuta
        1. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
          1. Takashi Watanabe
          1. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
            1. Kennichi Satoh
            1. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
              1. Akihiko Satoh
              1. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
                1. Morihisa Hirota
                1. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
                  1. Shin Hamada
                  1. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
                    1. Tooru Shimosegawa
                    1. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan

                      Abstract

                      Objective: There is a concept that pancreatitis results from an imbalance of proteases and their inhibitors within the pancreatic parenchyma. It has been recently shown that a loss-of-function variant c.571G>A (p.G191R) in the anionic trypsinogen (PRSS2) gene protects against chronic pancreatitis in European populations. We here examined the association of the G191R variant with pancreatic disorders in Japan.

                      Methods: Genomic DNA was prepared from 378 healthy controls and 604 patients with pancreatic disorders (241 patients with chronic pancreatitis, 174 with acute pancreatitis, and 189 with pancreatic neoplasm). Mutational analysis of the PRSS2 gene was performed by PCR-restriction fragment length polymorphism and direct sequencing.

                      Results: The heterozygous G191R variant was found in 3 of 241 (1.2 %) patients with chronic pancreatitis, in 7 of 174 (4.0 %) patients with acute pancreatitis, and in 12 of 189 (6.3 %) patients with pancreatic neoplasm. The G191R variant was found in 25 (2 were homozygous and 23 were heterozygous) of 378 (6.6 %) healthy controls. The G191R frequency in patients with chronic pancreatitis was lower than that in healthy controls (P=0.001; Odds ratio (OR) 0.178; 95 % confidence interval (CI)=0.057-0.561). The G191R frequency was lower in patients with alcoholic (0.9 %; P=0.015; OR 0.132; 95 % CI=0.022-0.779) and idiopathic (1.0 %; P=0.025; OR 0.144; 95 % CI=0.025-0.851) chronic pancreatitis than that in healthy controls. Patients with alcoholic acute pancreatitis (n=59) had no variant carrier, and the G191R frequency was lower than that in healthy controls (P=0.035).

                      Conclusion: The G191R variant protected against alcoholic and idiopathic chronic pancreatitis as well as alcoholic acute pancreatitis in Japan.

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