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The investigation of the frequency of the alpha-1-antitrypsin phenotype in patients with liver cirrhosis

  • Mehdi Afsharinasab , Amir Hossein Akbari , Vahid Mirzaei , Mehdi Mahmoodi , Mohammad Reza Hajizadeh , Jamal Amri ORCID logo and Alireza Khoshdel ORCID logo EMAIL logo
Published/Copyright: August 17, 2022
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Hormone Molecular Biology and Clinical Investigation
From the journal Hormone Molecular Biology and Clinical Investigation Volume 43 Issue 4

Abstract

Objectives

Alpha-1-antitrypsin (AAT) has different phenotypes. Evidence suggests that the abundance of each of these phenotypes may be associated with a disease. The purpose of this study was to evaluate the frequency of AAT phenotypes in patients with liver cirrhosis as well as in healthy individuals.

Methods

In this study, 42 patients with liver cirrhosis were selected. The results of the previous research done by the researcher on healthy individuals were used to construct the control group. After obtaining informed consent, 5 mL of fasting venous blood sample was taken, and phenotypes were analyzed by isoelectric focusing. Data were analyzed using Chi-square and Fisher’s exact tests at a significant level of 0.05.

Results

The results of this study indicated that all 42 healthy subjects had an MM allele (100%). However, among 42 patients, 35 (83.3%) had an MM allele, 5 (11.9%) had an MS allele, and 2 (4.8%) had MZ allele. The difference between the two groups was significant (p=0.02). There was no difference between men and women in the allele type (p=0.557).

Conclusions

This study revealed that MS and MZ alleles were observed only in patients with liver cirrhosis, and none of these alleles were found in healthy subjects. Therefore, MS and MZ alleles can be further investigated as risk factors for liver cirrhosis.

Keywords: alpha-1-antitrypsin; liver cirrhosis; phenotypes
Corresponding author: Dr. Alireza Khoshdel, Department of Clinical Biochemistry, Nervous System Stem Cells Research Center, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran; and Department of Clinical Biochemistry, Faculty of Medicine, and Pistachio Safety Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran, Phone: +982333441022, Fax: 02333654209, E-mail:

Acknowledgments

The authors would like to thank the Rafsanjan University of Medical Sciences (RUMS) for financial support.

  1. Research funding: This work was supported by funds from the Arak University of Medical Sciences (Grant number: 20.1240).

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The present study was approved by Review Board and Ethics Committee of Rafsanjan University of Medical Sciences, Iran.

References

1. Ramachandran, P, Dobie, R, Wilson-Kanamori, J, Dora, E, Henderson, B, Luu, N, et al.. Resolving the fibrotic niche of human liver cirrhosis at single-cell level. Nature 2019;575:512–8. https://doi.org/10.1038/s41586-019-1631-3.Search in Google Scholar PubMed PubMed Central

2. Rezaei, N, Asadi-Lari, M, Sheidaei, A, Khademi, S, Gohari, K, Delavari, F, et al.. Liver cirrhosis mortality at national and provincial levels in Iran between 1990 and 2015: a meta regression analysis. PLoS One 2019;14:1–13. https://doi.org/10.1371/journal.pone.0198449.Search in Google Scholar PubMed PubMed Central

3. Organization, WH. Age-standardized death rates of liver cirrhosis. In: Global health observatory; 2014, United States. Available from: http://www.who.int/gho/alcohol/harms_consequences/deaths_liver_cirrhosis/en/indexhtml.Search in Google Scholar

4. Hawkey, C, Bosch, J, Richter, JE, Garcia-Tsao, G, Chan, FK. Textbook of clinical gastroenterology and hepatology. John Wiley & Sons; 2012.10.1002/9781118321386Search in Google Scholar

5. Kamimura, K, Sakamaki, A, Kamimura, H, Setsu, T, Yokoo, T, Takamura, M, et al.. Considerations of elderly factors to manage the complication of liver cirrhosis in elderly patients. World J Gastroenterol 2019;25:1817. https://doi.org/10.3748/wjg.v25.i15.1817.Search in Google Scholar PubMed PubMed Central

6. Ballester-Clau, R, Vicente, GT, Ramos, MC, Blanch, CA, Calafat, JMM, Comas, EP, et al.. Efficacy and safety of treatment with ferric carboxymaltose in patients with cirrhosis and gastrointestinal bleeding. Front Med 2020;7:128. https://doi.org/10.3389/fmed.2020.00128.Search in Google Scholar PubMed PubMed Central

7. Xu, H, Jiang, XM, Wu, Y, Li, YM, Zheng, YW, Ohkohchi, N. Prominent effect of platelet on improvement of liver cirrhosis. AME Case Rep 2020;4:1–4. https://doi.org/10.21037/acr.2020.04.02.Search in Google Scholar PubMed PubMed Central

8. Matamala, N, Martinez, MT, Lara, B, Perez, L, Vazquez, I, Jimenez, A, et al.. Alternative transcripts of the SERPINA1 gene in alpha-1 antitrypsin deficiency. J Transl Med 2015;13:211. https://doi.org/10.1186/s12967-015-0585-y.Search in Google Scholar PubMed PubMed Central

9. Pervakova, MY, Mazing, AV, Lapin, SV, Tkachenko, OY, Budkova, AI, Surkova, EA, et al.. High serum level of IL-17 in patients with chronic obstructive pulmonary disease and the alpha-1 antitrypsin PiZ allele. Pulm Med 2020;2020:1–6.10.1155/2020/9738032Search in Google Scholar PubMed PubMed Central

10. Aiello, M, Fantin, A, Longo, C, Ferrarotti, I, Bertorelli, G, Chetta, A. Clinical manifestations in patients with PI* MMMalton genotypes. A matter still unsolved in alpha-1 antitrypsin deficiency. Respirol Case Rep 2020;8:1–5. https://doi.org/10.1002/rcr2.528.Search in Google Scholar PubMed PubMed Central

11. Karadagi, A, Cavedon, AG, Zemack, H, Nowak, G, Eybye, ME, Zhu, X, et al.. Systemic modified messenger RNA for replacement therapy in alpha 1-antitrypsin deficiency. Sci Rep 2020;10:1–11. https://doi.org/10.1038/s41598-020-64017-0.Search in Google Scholar PubMed PubMed Central

12. Hunt, A, Glasgow, A, Humphreys, H, Greene, CM. Alpha-1 antitrypsin—a target for MicroRNA-based therapeutic development for cystic fibrosis. Int J Mol Sci 2020;21:836. https://doi.org/10.3390/ijms21030836.Search in Google Scholar PubMed PubMed Central

13. Ponce-Gallegos, MA, Pérez-Rubio, G, García-Carmona, A, García-Gómez, J, Hernández-Zenteno, R, Ramírez-Venegas, A, et al.. Haplotype in SERPINA1 (AAT) is associated with reduced risk for COPD in a Mexican mestizo population. Int J Mol Sci 2020;21:195.10.3390/ijms21010195Search in Google Scholar PubMed PubMed Central

14. Gómez-Mariano, G, Matamala, N, Martínez, S, Justo, I, Marcacuzco, A, Jimenez, C, et al.. Liver organoids reproduce alpha-1 antitrypsin deficiency-related liver disease. Hepatol Int 2020;14:127–37. https://doi.org/10.1007/s12072-019-10007-y.Search in Google Scholar PubMed PubMed Central

15. Cummings, EE, O’Reilly, LP, King, DE, Silverman, RM, Miedel, MT, Luke, CJ, et al.. Deficient and null variants of SERPINA1 are proteotoxic in a caenorhabditis elegans model of α1-antitrypsin deficiency. PLoS One 2015;10:1–22. https://doi.org/10.1371/journal.pone.0141542.Search in Google Scholar PubMed PubMed Central

16. Gramegna, A, Aliberti, S, Confalonieri, M, Corsico, A, Richeldi, L, Vancheri, C, et al.. Alpha-1 antitrypsin deficiency as a common treatable mechanism in chronic respiratory disorders and for conditions different from pulmonary emphysema? A commentary on the new european respiratory society statement. Multidiscip Respir Med 2018;13:39. https://doi.org/10.1186/s40248-018-0153-4.Search in Google Scholar PubMed PubMed Central

17. Greulich, T, Rodríguez-Frias, F, Belmonte, I, Klemmer, A, Vogelmeier, CF, Miravitlles, M. Real world evaluation of a novel lateral flow assay (AlphaKit® QuickScreen) for the detection of alpha-1-antitrypsin deficiency. Respir Res 2018;19:151. https://doi.org/10.1186/s12931-018-0826-8.Search in Google Scholar PubMed PubMed Central

18. Al Ashry, HS, Strange, C. COPD in individuals with the PiMZ alpha-1 antitrypsin genotype. Eur Respir Rev 2017;26. https://doi.org/10.1183/16000617.0068-2017.Search in Google Scholar PubMed PubMed Central

19. Jaruvongvanich, V, Spanuchart, I, Scott Gallacher, T. Ruptured gastric aneurysm in alpha-1 antitrypsin deficiency. ACG Case Rep J 2016;3:e118.10.14309/crj.2016.91Search in Google Scholar PubMed PubMed Central

20. Tanash, HA, Ekstrom, M, Wagner, P, Piitulainen, E. Cause-specific mortality in individuals with severe alpha 1-antitrypsin deficiency in comparison with the general population in Sweden. Int J Chron Obstruct Pulmon Dis 2016;11:1663–9.10.2147/COPD.S109173Search in Google Scholar PubMed PubMed Central

21. Fischer, H-P, Ortiz-Pallardó, ME, Ko, Y, Esch, C, Zhou, H. Chronic liver disease in heterozygous α1-antitrypsin deficiency PiZ. J Hepatol 2000;33:883–92. https://doi.org/10.1016/s0168-8278(00)80119-1.Search in Google Scholar PubMed

22. Graziadei, IW, Joseph, JJ, Wiesner, RH, Therneau, TM, Batts, KP, Porayko, MK. Increased risk of chronic liver failure in adults with heterozygous α-antitrypsin deficiency. Hepatology 1998;28:1058–63. https://doi.org/10.1002/hep.510280421.Search in Google Scholar PubMed

23. Antoury, C, Lopez, R, Zein, N, Stoller, JK, Alkhouri, N. Alpha-1 antitrypsin deficiency and the risk of hepatocellular carcinoma in end-stage liver disease. World J Hepatol 2015;7:1427. https://doi.org/10.4254/wjh.v7.i10.1427.Search in Google Scholar PubMed PubMed Central

24. Guo, S, Booten, SL, Aghajan, M, Hung, G, Zhao, C, Blomenkamp, K, et al.. Antisense oligonucleotide treatment ameliorates alpha-1 antitrypsin-related liver disease in mice. J Clin Invest 2014;124:251–61.10.1172/JCI67968Search in Google Scholar PubMed PubMed Central

25. Budin, C, Rivet, C, Dumortier, J, Legall, C, Bouvier, R, Lachaux, A. Cirrhosis in children and SZ phenotype alpha1-antitrypsin deficiency. Gastroenterol Clin Biol 2005;29:206–7.10.1016/S0399-8320(05)80740-7Search in Google Scholar PubMed

26. Ghoreishi, AS, Mahmoodi, M, Khoshdel, A. Comparison of alpha 1- antitrypsin activity and phenotype in type 1 diabetic patients to healthy individuals. Fam Med Prim Care Rev 2022;11:1377–81. https://doi.org/10.4103/jfmpc.jfmpc_905_21.Search in Google Scholar PubMed PubMed Central

27. Gurau, G, Coman, M, Dinu, CA, Busila, C, Voicu, DC, Macovei, LA, et al.. The electrophoretic patterns of serum proteins in children. Rev Chim 2016;67:190–4.Search in Google Scholar

28. Al-Jameil, N, Hassan, AA, Buhairan, A, Hassanato, R, Isac, SR, Al-Otaiby, M, et al.. Genotyping diagnosis of alpha-1 antitrypsin deficiency in Saudi adults with liver cirrhosis. Medicine 2017;96:1–8. https://doi.org/10.1097/md.0000000000006071.Search in Google Scholar PubMed PubMed Central

29. Kumar, R, Derbigny, WA. Cellulose acetate electrophoresis of hemoglobin. Methods Mol Biol 2019;1855:81–5.10.1007/978-1-4939-8793-1_7Search in Google Scholar PubMed

30. Schaefer, B, Mandorfer, M, Viveiros, A, Finkenstedt, A, Ferenci, P, Schneeberger, S, et al.. Heterozygosity for the alpha-1-antitrypsin Z allele in cirrhosis is associated with more advanced disease. Liver Transpl 2018;24:744–51.10.1002/lt.25057Search in Google Scholar PubMed PubMed Central

31. Eriksson, S, Carlson, J, Velez, R. Risk of cirrhosis and primary liver cancer in alpha1-antitrypsin deficiency. N Engl J Med 1986;314:736–9.10.1056/NEJM198603203141202Search in Google Scholar PubMed

32. Cacciottolo, TM, Gelson, WT, Maguire, G, Davies, SE, Griffiths, WJ. Pi*Z heterozygous alpha-1 antitrypsin states accelerate parenchymal but not biliary cirrhosis. Eur J Gastroenterol Hepatol 2014;26:412–7. https://doi.org/10.1097/meg.0000000000000061.Search in Google Scholar

33. Lomas, DA, Hurst, JR, Gooptu, B. Update on alpha-1 antitrypsin deficiency: new therapies. J Hepatol 2016;65:413–24. https://doi.org/10.1016/j.jhep.2016.03.010.Search in Google Scholar PubMed

34. Gorska, K, Korczynski, P, Struniawski, R, Krenke, R, Oldakowska-Jedynak, U, Grabczak, EM, et al.. Heterozygous alpha1antitrypsin deficiency in liver transplant candidates. Pol Arch Med Wewn 2013;123:14–20.10.20452/pamw.1583Search in Google Scholar

35. Carey, EJ, Iyer, VN, Nelson, DR, Nguyen, JH, Krowka, MJ. Outcomes for recipients of liver transplantation for alpha-1-antitrypsin deficiency-related cirrhosis. Liver Transplant 2013;19:1370–6. https://doi.org/10.1002/lt.23744.Search in Google Scholar PubMed

36. Nelson, DR, Teckman, J, Di Bisceglie, AM, Brenner, DA. Diagnosis and management of patients with α1-antitrypsin (A1AT) deficiency. Clin Gastroenterol Hepatol 2012;10:575–80. https://doi.org/10.1016/j.cgh.2011.12.028.Search in Google Scholar PubMed PubMed Central

37. Piitulainen, E, Carlson, J, Ohlsson, K, Sveger, T. Alpha1-antitrypsin deficiency in 26-year-old subjects: lung, liver, and protease/protease inhibitor studies. Chest 2005;128:2076–81. https://doi.org/10.1378/chest.128.4.2076.Search in Google Scholar PubMed

38. Yoon, D, Kueppers, F, Genta, RM, Klintmalm, GB, Khaoustov, VI, Yoffe, B. Role of alpha-1-antichymotrypsin deficiency in promoting cirrhosis in two siblings with heterozygous alpha-1-antitrypsin deficiency phenotype SZ. Gut 2002;50:730–2. https://doi.org/10.1136/gut.50.5.730.Search in Google Scholar PubMed PubMed Central

39. Pittschieler, K. Liver disease and heterozygous alpha-1-antitrypsin deficiency. Acta Pædiatrica 1991;80:323–7. https://doi.org/10.1111/j.1651-2227.1991.tb11856.x.Search in Google Scholar PubMed

40. de Serres, FJ, Blanco, I. Prevalence of alpha1-antitrypsin deficiency alleles PI*S and PI*Z worldwide and effective screening for each of the five phenotypic classes PI*MS, PI*MZ, PI*SS, PI*SZ, and PI*ZZ: a comprehensive review. Ther Adv Respir Dis 2012;6:277–95. https://doi.org/10.1177/1753465812457113.Search in Google Scholar PubMed

41. Lotfi, AS, MohammadianYajloo, M, MesbahNamin, S, Hasannia, S, Beiglarzadeh, M, GholamhoseinGoodarzi, B. The frequency of the alpha-1-antitrypsin M1, M2, M3, S and Z variants in Iranian population. JRUMS 2005;4:35–9.Search in Google Scholar

42. Kheirollah, A, Zahraei, M. The study of alterations of alpha–1–antitrypsin (1-AT) in serum of hypothyroid patients. Avicenna J Clin Med 1998;5:1–10.Search in Google Scholar

43. Mitchell, EL, Khan, Z. Liver disease in alpha-1 antitrypsin deficiency: current approaches and future directions. Curr Pathobiol Rep 2017;5:243–52. https://doi.org/10.1007/s40139-017-0147-5.Search in Google Scholar PubMed PubMed Central

44. Wang, Q, Du, J, Yu, P, Bai, B, Zhao, Z, Wang, S, et al.. Hepatic steatosis depresses alpha-1-antitrypsin levels in human and rat acute pancreatitis. Sci Rep 2015;4:17833. https://doi.org/10.1038/srep17833.Search in Google Scholar PubMed PubMed Central

45. Casas, F, Blanco, I, Martinez, MT, Bustamante, A, Miravitlles, M, Cadenas, S, et al.. Indications for active case searches and intravenous alpha-1 antitrypsin treatment for patients with alpha-1 antitrypsin deficiency chronic pulmonary obstructive disease: an update. Arch Bronconeumol 2015;51:185–92. https://doi.org/10.1016/j.arbr.2014.12.006.Search in Google Scholar

46. Kishimoto, Y, Yamada, S, Hirayama, C. An association between alpha 1-antitrypsin phenotype and chronic liver disease. Hum Genet 1990;84:132–6. https://doi.org/10.1007/bf00208927.Search in Google Scholar PubMed

47. Brunt, PW. Antitrypsin and the liver. Gut 1974;15:573–80. https://doi.org/10.1136/gut.15.7.573.Search in Google Scholar PubMed PubMed Central

48. Tanash, HA, Piitulainen, E. Liver disease in adults with severe alpha-1-antitrypsin deficiency. J Gastroenterol 2019;54:541–8. https://doi.org/10.1007/s00535-019-01548-y.Search in Google Scholar PubMed PubMed Central

49. Topic, A, Alempijevic, T, Milutinovic, AS, Kovacevic, N. Alpha-1-antitrypsin phenotypes in adult liver disease patients. Ups J Med Sci 2009;114:228–34. https://doi.org/10.3109/03009730903243472.Search in Google Scholar PubMed PubMed Central

Received: 2022-01-04
Accepted: 2022-05-23
Published Online: 2022-08-17

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/hmbci-2022-0001
Keywords for this article
alpha-1-antitrypsin; liver cirrhosis; phenotypes

Articles in the same Issue

  1. Frontmatter
  2. Letter to the Editor
  3. COVID-19 pandemic: transmission of SARS-CoV-2 in animals, a risk for human beings
  4. Original Articles
  5. Anti Mullerian hormone as a diagnostic tool for polycystic ovary syndrome in women of reproductive age with morbid obesity
  6. Potential tumor marker for hepatocellular carcinoma identification: PI3K and pro-inflammatory cytokines (TGF-β, IL-1, and IL-6)
  7. The investigation of the frequency of the alpha-1-antitrypsin phenotype in patients with liver cirrhosis
  8. Anti-oxidant effect of metformin through AMPK/SIRT1/PGC-1α/SIRT3– independent GPx1 expression in the heart of mice with endometriosis
  9. Hypoxia-inducible factor-1α and ischemia-modified albumin levels in intensive care COVID-19 Patients
  10. Association between TP53 Arg72Pro variant and recurrent pregnancy loss in the Greek population
  11. Selective estrogen receptor α and β antagonist aggravate cardiovascular dysfunction in type 2 diabetic ovariectomized female rats
  12. Adrenocorticotropic hormone (ACTH) level and adrenal deficiency in patients with mucocutaneous pemphigus
  13. The effect of resistance training on serum levels of sex hormones and sperm quality in male rats under X-ray radiation
  14. The effect of high-intensity interval training on serum and adipose tissues vaspin levels in rats fed a high-fat high-sucrose diet
  15. Anti-migratory effect of curcumin on A-549 lung cancer cells via epigenetic reprogramming of RECK/ matrix metalloproteinase axis
  16. Efficacy of rectal progesterone on maternal and neonatal outcomes in pregnant women with Preterm Premature Rupture of membranes: a triple-blind randomised clinical trial
  17. Case Report
  18. Ovarian tissue cryopreservation in Malaysia: a case series
  19. Review Articles
  20. An overview of prognostic value of neurologic and cardiac biomarkers in patients with COVID-19 sequelae
  21. Potential role of melatonin in prevention and treatment of lung cancer
  22. Esketamine–A quick-acting novel antidepressant without the disadvantages of ketamine
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