Preview

Medical Genetics

Advanced search

Joint contribution of alcohol abuse and the rs6580502 polymorphism of the SPINK1 gene to the risk of acute alcoholic pancreatitis

https://doi.org/10.25557/2073-7998.2021.04.43-48

Abstract

The main risk factor for the acute non-biliary pancreatitis is alcohol abuse. Alcohol initiates exocrine hypersecretion of the pancreas, creates the prerequisites for increasing pressure in the ducts. Enzymes activate proteolytic enzymes and cause autolysis of pancreatic cells. With an excessive accumulation of trypsin in the tissues, the digestion of the tissues of the gland by its own enzymes begins. SPINK1, a pancreatic secretory trypsin inhibitor, prevents premature activation of zymogens. Aim: to determine the contribution of the rs6580502 polymorphism of the SPINK1 gene and alcohol abuse in the development of acute pancreatitis and its complications. DNA samples obtained from 471 unrelated patients with acute non-biliary pancreatitis and 573 unrelated individuals without gastrointestinal diseases. Genotyping was performed using the PCR method with discrimination of alleles using TaqMan probes. The χ2 criterion and the odds ratio (OR) with 95% confidence intervals (CI) were used to assess the associations of alleles and genotypes of genes with the risk of developing the disease. Statistical analysis was carried out using the Statistica 6.0 software (StatSoft, USA). We found an association of the T/T SPINK1 rs6580502 genotype with an increased risk of developing acute non-biliary pancreatitis (corOR (95% CI)= 1.69 (1.22-2.33); p=0,0015R). In carriers of the TT genotype, the risk of developing SNP was increased by such risk factors as the frequency of drinking more than 2 times per week (corOR (95% CI)= 1,66(1,08-2,57); p=0,02R) and the volume of alcohol consumption more than 200 grams per week (corOR (95% CI)= 6,04(1,81-20,17); p= 0,001R). An association of the T/T genotype with an increased risk of developing edematous pancreatitis was also revealed (corOR (95% CI)= 2.10 (1.44-3.05); Р= 1×10-4 R).

About the Authors

T. A. Samgina
Kursk State Medical University
Russian Federation


D. I. Kolmykov
Kursk State Medical University
Russian Federation


G. N. Myasnyankina
Kursk State Medical University
Russian Federation


Iu. E. Azarova
Kursk State Medical University
Russian Federation


Yu. V. Kanishchev
Kursk State Medical University
Russian Federation


P. M. Nazarenko
Kursk State Medical University
Russian Federation


A. V. Polonikov
Kursk State Medical University
Russian Federation


V. A. Lazarenko
Kursk State Medical University
Russian Federation


References

1. Филин В.И., Костюченко А.Л. Неотложная панкреатология: Справочник для врачей. -Санкт-Петербург: Питер, 1994. 410 с.

2. Шалимов А.А., Шалимов С.А., Ничитайло М.Е., Радзиховский А.П. Хирургия поджелудочной железы. Симферополь: Таврида, 1997. 560 с.

3. Cruickhank A.H. Non-infective acute pancreatitis. Pathology of Pancreas.1995:12.

4. Sleinberg W., Tenner S. Acute pancreatitis. Engl. Joum. Med.1994;310(17):1198-1209.

5. Маев И.В. Наследственный панкреатит. Российский журнал гастроэнтерологии, гепатологии и колопроктологии. 2004; 1: 20-25.

6. Witt H. Chronic pancreatitis and cystic fibrosis. Gut. 2003; 52(suppl 2): ii31-ii41.

7. Gorry M.C., Gabbaizedeh D., Furey W., et al. Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis. Gastroenterology. 1997; 113(4):1063-1068.

8. Figarella C., Amouric M., Guy-Crotte O. Enzyme activation and liberation: intracellular /extracellular events / Acute pancreatitis: research and clinical management. Eds. Beger HG, Buchler M. Berlin:Springer.Verlag.1987:53-60.

9. Király O., Boulling A., Witt H., et al. Signal peptide variants that impair secretion of pancreatic secretory trypsin inhibitor (SPINK1) cause autosomal dominant hereditary pancreatitis. Human mutation. 2007; 28(5): 469-476. doi: 10.1002/humu.20471

10. Witt H., Luck W., Becker M., et al. Mutation in the SPINK1 trypsin inhibitor gene, alcohol use, and chronic pancreatitis. Jama.2001; 285(21), 2716-2717. doi:10.1001/jama.285.21.2716-a

11. Aoun E., Chang C.C.H., Greer J.B. et al. C. Pathways to injury in chronic pancreatitis: decoding the role of the high-risk SPINK1 N34S haplotype using meta-analysis. PLoS One. 2008;3(4), e2003. doi: 10.1371/journal.pone.0002003

12. Hirota M., Kuwata K., Ohmuraya M., Ogawa M. From acute to chronic pancreatitis: the role of mutations in the pancreatic secretory trypsin inhibitor gene. Jop. 2003;4(2), 83-88.

13. Tukiainen E., Kylänpää M.L., Kemppainen E., et al. Pancreatic secretory trypsin inhibitor (SPINK1) gene mutations in patients with acute pancreatitis. Pancreas. 2005;30(3), 239-242. doi: 10.1097/01.mpa.0000157479.84036.ed

14. Chandak G. R., Idris M. M., Reddy D. N., Mani K. R., et al. Absence of PRSS1 mutations and association of SPINK1 trypsin inhibitor mutations in hereditary and non-hereditary chronic pancreatitis. Gut. 2004;53(5), 723-728. doi: 10.1136/gut.2003.026526

15. Schneider A. Serine protease inhibitor Kazal type 1 mutations and pancreatitis. Clinics in laboratory medicine. 2005;25(1), 61-78. doi:10.1016/j.cll.2004.12.005

16. Bernardino A. L., Guarita D. R., Mott C. B., Pedroso M. R., et al. CFTR, PRSS1 and SPINK1 mutations in the development of pancreatitis in Brazilian patients. Jop, 2003;4(5), 169-77.

17. Lee K. H., Ryu J. K., Yoon W. J., Lee J. K., et al. Mutation analysis of SPINK1 and CFTR gene in Korean patients with alcoholic chronic pancreatitis. Digestive diseases and sciences.2005; 50(10), 1852-1856. doi: 10.1007/s10620-005-2950-9

18. Le Marechal C., Chen J. M., Le Gall C., Plessis G., et al. Two novel severe mutations in the pancreatic secretory trypsin inhibitor gene (SPINK1) cause familial and/or hereditary pancreatitis. Human mutation.2004; 23(2), 205-205. doi: 10.1002/humu.9212

19. Whitcomb D.C., Yadav D., Adam S., et al. Multicenter approach to recurrent acute and chronic pancreatitis in the United States: the North American Pancreatitis Study 2 (NAPS2). Pancreatology. 2008; 8(4-5):520-531. doi: 10.1159/000152001

20. Brewer R.D., Morris P.D., Cole T.B. et al. The risk of dying in alcohol-related automobile crashes among habitual drink drivers. Engl J Med.1994;331:513-517. doi: 10.1056/NEJM199408253310806

21. Polonikov A.V., Samgina T.A., Nazarenko P.M. et al. Alcohol consumption and cigarette smoking are important modifiers of the association between acute pancreatitis and the PRSS1-PRSS2 locus in men. Pancreas. 2017;46(2): 230-236. doi: 10.1097/MPA.0000000000000729

22. Schneider A., Pfützer R.H., Barmada M.M. et al. Limited contribution of the SPINK1 N34S mutation to the risk and severity of alcoholic chronic pancreatitis: a report from the United States. Digestive diseases and sciences. 2003;48(6): 1110-1115. doi: 10.1023/A:1023768829772

23. Witt H., Luck W., Becker M. et al. Mutation in the SPINK1 trypsin inhibitor gene, alcohol use, and chronic pancreatitis. Jama, 2001; 285(21):2716-2717. doi:10.1001/jama.285.21.2716-a

24. Kume K., Masamune A., Mizutamari H. et al. Mutations in the serine protease inhibitor Kazal Type 1 (SPINK1) gene in Japanese patients with pancreatitis. Pancreatology. 2005; 5(4-5): 354-360. doi: 10.1159/000086535

25. Kereszturi É., Sahin-Tóth M. Pancreatic cancer cell lines heterozygous for the SPINK1 p. N34S haplotype exhibit diminished expression of the variant allele. Pancreas. 2017; 46(6):54. doi: 10.1097/MPA.0000000000000817

26. Kereszturi E., Kiraly O., Sahin-Toth M. Minigene analysis of intronic variants in common SPINK1 haplotypes associated with chronic pancreatitis. Gut. 2009; 58(4):545-549. doi: 10.1136/gut.2008.170191

27. Tang X.Y., Lin J.H., Zou W.B. Toward a clinical diagnostic pipeline for SPINK1 intronic variants. Human genomics. 2019; 13(1): 8. doi:10.1186/s40246-019-0193-7


Review

For citations:


Samgina T.A., Kolmykov D.I., Myasnyankina G.N., Azarova I.E., Kanishchev Yu.V., Nazarenko P.M., Polonikov A.V., Lazarenko V.A. Joint contribution of alcohol abuse and the rs6580502 polymorphism of the SPINK1 gene to the risk of acute alcoholic pancreatitis. Medical Genetics. 2021;20(4):43-48. (In Russ.) https://doi.org/10.25557/2073-7998.2021.04.43-48

Views: 307


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2073-7998 (Print)