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Contribution polymorphism (rs55754655) aldehyde oxidase gene in the development of acute pancreatitis

Abstract

Acute pancreatitis (AP) is a multifactorial disease, the development of which is determined by a complex interaction of multiple genes and various environmental factors, questions relating to genetic mechanisms of AP and its complications have been studied are not enough. An important role in the development of acute pancreatitis is given the action of toxic substances and disruption of the regulation of pro- and antioxidant protection. One of prooxidant enzymes is aldehyde oxidase (AOX1), which plays a substantial role in the metabolism of xenobiotics, drugs and ethanol degradation products. Aldehyde oxidase gene was not considered as a possible candidate susceptibility to acute pancreatitis, although the pathogenetic significance of AOX1 gene against acute pancreatitis is obvious. The aim of this study was to investigate the relationship between polymorphism (rs55754655) AOX1 gene and risk of acute pancreatitis in Russian population. Whole blood samples were obtained from 311 AP patients and 238 healthy controls. Genotyping of polymorphisms (rs55754655) AOX1 gene was performed through a TaqMan assay. Genotype А/G (OR = 1.83 95% CI 1.06-3.17 p = 0.03) was significantly associated with the risk of AP. Stratified analysis showed that the genotype A / G was associated with development of acute pancreatitis in women (OR = 3.36 95% CI 1.25-9.01 p = 0.01). Statistically significant differences in the frequencies of alleles and genotypes of polymorphism in groups of smokers and non-smokers are not installed. It was found that the amount and frequency of administration of alcohol did not change the overall picture of genotype associations with the risk of acute pancreatitis. However, patients with genotype A/G with a history of alcohol drinking 10 or more years have the highest risk to the developing pancreatitis (OR = 2.63 95% CI 1.21-5.7, p = 0.01).

About the Authors

T. A. Samgina
Kursk State Medical University
Russian Federation


O. Yu. Bushueva
Kursk State Medical University
Russian Federation


Yu. V. Kanischev
Kursk State Medical University
Russian Federation


S. N. Grigorjev
Kursk State Medical University
Russian Federation


P. M. Nazarenko
Kursk State Medical University
Russian Federation


A. V. Polonikov
Kursk State Medical University
Russian Federation


References

1. Горский ВА, Ковальчук ЛВ, Агапов МА. Антимедиаторная терапия в комплексном лечении острого деструктивного панкреатита. Хирургия.- 2010.- №3.- С.54-61.

2. LaRusch J, Whitcomb DC. Genetics of pancreatitis. Curr.Opin.Gastroenterol.- 2011.-№27.- С.467-474.

3. Cho SM, Shin S, Lee KA. PRSS1, SPINK1, CFTR, and CTRC Pathogenic Variants in Korean Patients With Idiopathic Pancreatitis. Ann Lab Med. 2016 Nov;36(6):555-60.

4. Wang W, Sun XT, Weng XL. et al. Comprehensive screening for PRSS1, SPINK1, CFTR, CTRC and CLDN2 gene mutations in Chinese paediatric patients with idiopathic chronic pancreatitis: a cohort study. BMJ Open 2013;3: e003150.

5. Masamune A, Nakano E, Kume K. et al. PRSS1 c.623G>C (p.G208A) variant is associated with pancreatitis in Japan. Gut 2014;63:366.

6. Самгина ТА, Бушуева ОЮ, Назаренко ПМ, Полоников АВ. Связь полиморфизма HindIII гена липопротеинлипазы с развитием острого небилиарного панкреатита: пилотное исследование. Бюллетень экспериментальной биологии и медицины.2016-№1.-С.92-96.

7. Ockenga J, Strunck S, Post C et al. The role of epoxide hydrolase Y113H gene variant in pancreatic diseases.-Pancreas. 2009.- May;38(4): 97-101.

8. Yin YW, Sun QQ, Feng JQ et al. Influence of interleukin gene polymorphisms on development of acute pancreatitis: asystematic review and meta-analysis /Mol. Biol. Rep.- 2013 Oct;40(10):5931-5941.

9. Самгина ТА, Бушуева ОЮ, Назаренко ПМ, Полоников АВ. Связь промоторного полиморфизма -308 G>A гена фактора некроза опухоли с тяжестью течения острого панкреатита у русской популяции жителей курской области// Экспериментальная и клиническая гастроэнтерология. - 2014. - № 9. - С. 17-20.

10. Баранов ВС, Баранова ЕВ, Иващенко ТЕ. Геном человека и гены предрасположености. Введение в предиктивную медицину. СПб.: Интермедика, 2000. - 272 с.

11. Enrico Garattini, Maddalena Fratelli, Mineko Terao. The mammaliannal dehydeoxidase gene family -HumGenomics. 2009; 4(2): 119-130.

12. GeneAtlas U133A, gcrma

13. Floyd A, Pedersen L, Nielsen GL et al. Risk of acute pancreatitis in users of azathioprine: a population-based case-control study. Am J Gastroenterol. 2003 Jun;98(6):1305-8.

14. Teich N, Mohl W, Bokemeyer B. et al. German IBD Study Group. Azathioprine-induced Acute Pancreatitis in Patients with Inflammatory Bowel Diseases-A Prospective Study on Incidence and Severity.-J Crohns Colitis. 2016 Jan;10(1):61-8.

15. Fu C, Di L, Han X et al. Aldehyde oxidase 1 (AOX1) in human liver cytosols: quantitative characterization of AOX1 expression level and activity relationship. Drug Metab Dispos. 2013 Oct;41(10):1797-804.

16. Banks P.A., Bollen T.L., Dervenis C., Gooszen H.G. et al. Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis 2012: revision of the Atlanta classification and definitions by international consensus // Gut. 2013. Vol.62, N 1. P. 102-111.

17. Furtwaengler NA, de Visser RO. Lack of international consensus in low-risk drinking guidelines. Drug Alcohol Rev. 2013;32:11-18.

18. Mateusz Kurzawski, Krzysztof Dziewanowski, Krzysztof Safranow and Marek Drozdzik-The Polymorphism of Genes Involved in Purine Metabolism (XDH, AOX1, MOCOS) in Kidney Transplant Recipients Receiving Azathioprine. Drug Monit 2012;34:266-274.

19. Smith MA, Marinaki AM, Arenas M. et al. Novel pharmacogenetic markers for treatment outcome inazathioprine-treated inflammatory bowel disease. Aliment.Pharmacol.Ther.30, P.375-384.

20. Tobias Hartmann, Mineko Terao, Enrico Garattini et al. The Impact of Single Nucleotide Polymorphisms on Human Aldehyde Oxidase. Drug Metab Dispos. 2012 May; 40(5): 856-864.

21. Obach RS, Huynh P, Allen MC, Beedham C. Human liver aldehyde oxidase: inhibition by 239 drugs. J Clin Pharmacol. 2004 Jan;44(1):7-19.


Review

For citations:


Samgina T.A., Bushueva O.Yu., Kanischev Yu.V., Grigorjev S.N., Nazarenko P.M., Polonikov A.V. Contribution polymorphism (rs55754655) aldehyde oxidase gene in the development of acute pancreatitis. Medical Genetics. 2017;16(4):35-39. (In Russ.)

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