ASSOCIATION OF COMPLEMENTFACTOR H GENE (CFH) SINGLE NUCLEOTIDE POLYMORPHISM WITH RECURRENT APHTHUS STOMATITIS

AHMED MOHAMMED SALIH; HALIZ SADDEQ HASAN; SOLEEN SARDAR ZUHDIN; ABDULRAZZAQ MOHAMMED ABDULRAHMAN

AHMED MOHAMMED SALIH Department of Microbiology, College of Medicine, University of Duhok, Kurdistan Region, Iraq
HALIZ SADDEQ HASAN Department of Microbiology, College of Medicine, University of Duhok, Kurdistan Region, Iraq.
SOLEEN SARDAR ZUHDIN Duhok Medical Research Center, College of Medicine, University of Duhok, Kurdistan Region, Iraq
ABDULRAZZAQ MOHAMMED ABDULRAHMAN Dental Care Center, Duhok, Kurdistan region, Iraq

Keywords: Recurrent aphthus stomatitis, RAS, CFH, Tyr402His, oral mucosa

Abstract

https://doi.org/10.31386/dmj.uod.18.12.1.9

Background: Recurrent aphthous stomatitis (RAS) is a common chronic inflammation affecting oral mucosa that lead to mucosal ulceration. The causes are unclear, but dysregulation of the immune response has been proposed to be implicated in the development of the disease. In this study, we hypothesized that RAS is provoked by the dysregulation of the complement system, through the impairment of the function of complement regulatory proteins, the present study has aimed to investigate the impact of CFH gene SNPs that encodes the production of complement factor H in RAS development. Subject and Methods: Blood samples from 46 patientswith recurrent aphthus stomatitis were collected including 35 males and 11 females and 46 age and sex matched apparently healthy (with healthy oral cavity) volunteersincluding 23 males and 23 females were involved as a control group. Gnomic DNA was extractedfrom each blood sampleusing the isopropanol/ethanol method. Specific primers were used to amplify the CFH gene fragment that harbors the rs1061170 site encoding theTyr402 aminoacid. The PCR products were digested with NlaIII restriction enzyme. Results: A significant difference was found between the age groups among the RAS patients in regard to the severity of and recurrence of the RAS episodes, it was found to be higher significantly among the age group (20-30 years) compared to other age groups among RAS patients. Out of the 46 RAS patients, the CFH single nucleotide polymorphism (SNP), Tyr402His polymorphism variant was detected in 18 (39.1%); 11 (23.9%) females and 7 (15.2%) males, represented as 8 (17.4%) Tyr/His heterozygous variants and 10 (21.7%) were His/His homozygous variant. Among the 46 healthy control group, the CFH single nucleotide polymorphism (SNP), (Tyr402His polymorphism variant) was detected in 6 (13%) all of them were Tyr402His variant, 2 (4.3%) males and 4 (8.7%) females. There was a significant difference in the CFH (Tyr/His, His/His) variants rates between the RAS group and the healthy control group (p <0.05), but there was no significant difference of CFH (Tyr/His, His/His) variants rates between the males and females in the RAS group. Conclusions: We suggest that Tyr402Hispolymorphism can be considered as a risk factor for the RAS development, and His204His variant is more associated with the disease, however, more studies are recommended to be conducted on a larger sample size to confirm these evidences.

Downloads

Download data is not yet available.

References

1. Porter SR, Scully C, Pedersen A. Recurrent aphthous stomatitis. Crit Rev Oral Biol Med. 1998;9(3):306–321.
2. Sunday O. Akintoye, Martin S. Greenberg. Recurrent Aphthous Stomatitis. Dent Clin North Am. 2014 ; 58(2): 281–297.
3. Rogers RS., 3rd Recurrent aphthous stomatitis: clinical characteristics and associated systemic disorders. Semin Cutan Med Surg. 1997 Dec;16(4):278–283.
4. Ship JA, Chavez EM, Doerr PA, Henson BS, Sarmadi M. Recurrent aphthous stomatitis. Quintessence Int. 2000 Feb;31(2):95–112.
5. Terkeltaub RA. Colchicine update. Semin Arthritis Rheum. 2009 Jun;38(6):411–419.
6. Berkenstadt M, Weisz B, Cuckle H, Di-Castro M, Guetta E, Barkai G. Chromosomal abnormalities and birth defects among couples with colchicine treated familial Mediterranean fever. Am J Obstet Gynecol. 2005 Oct;193(4):1513–1516.
7. Lewkowicz N, Lewkowicz P, Dzitko K, Kur B, Tarkowski M, Kurnatowska A, Tchórzewski H. Dysfunction of CD4+CD25 high T regulatory cells in patients with recurrent aphthous stomatitis. J Oral Pathol Med. 2008 Sep;37(8):454–461.
8. Mohammad R, Halboub E, Mashlah A, Abou-Hamed H. Levels of salivary IgA in patients with minor recurrent aphthous stomatitis: a matched case-control study. Clinical oral investigations. 2013;17(3):975–980.
9. Lewkowicz N, Banasik M, Tchórzewski H. Predominance of production of Th1 type cytokines in recurrent aphthous ulceration. Dent Med Probl. 2004;42:655–660.
10. Borra RC, Andrade PM, Silva ID, I. D. C. G. Silva, A. Morgun, L.M.Weckx, A.S. Sminova, M. Franco. The Th1/Th2 immune-type response of the recurrent aphthous ulceration analyzed by cDNA microarray. J Oral Pathol Med. 2004;33:140–146.
11. Hietanen J, Häyrinen-Immonen R, Al-Samadi A, Koskenpato K, Konttinen YT. Recurrent aphthous ulcers—a Toll-like receptor-mediated disease?. J Oral Pathol Med. 2012;41:158–164.
12. Adinolfi M, Dobson NC, Bradwell AR. Synthesis of two components of human complement, beta 1H and C3bINA, during fetal life. Acta Paediatr Scand. 1981;70:705–710.
13. Agarwal S, Ferreira VP, Cortes C, Pangburn MK, Rice PA, Ram S. An Evaluation of the Role of Properdin in Alternative Pathway Activation on Neisseria meningitidis and Neisseria gonorrhoeae. J. Immunol. 2010; Jul 1;185(1):507-16. doi:10.4049 /jimmunol.0903598.
14. Ajona D, Hsu YF, Corrales L, Montuenga LM, Pio R. Down-regulation of human complement factor h sensitizes non-small cell lung cancer cells to complement attack and reduces in vivo tumor growth. J.Immunol. 2007;178:5991–5998.
15. Alsenz J, Lambris JD, Schulz TF, Dierich MP. Localization of the complement component C3b binding site and the cofactor activity for factor I in the 38 kDatryptic fragment of factor H. Biochem. J. 1984;224:389–398.
16. Areschoug T, Stalhammar-Carlemalm M, Karlsson I, Lindahl G. Streptococcal beta protein has separate binding sites for human factor H and IgA-Fc. J. Biol. Chem. 2002;277:12642–12648.
17. Kardys I, Klaver CC, Despriet DD. A common polymorphism in the complement factor H gene is associated with increased risk of myocardial infarction: the Rotterdam Study. J Am Coll Cardiol. 2006; 47: 1568-75.
18. Giannakis E, Jokiranta TS, Male DA, Ranganathan S, Ormsby RJ, Fischetti VA, Mold C, Gordon DL. A common site within factor H SCR 7 responsible for binding heparin, Creactive protein and streptococcal M protein. Eur J Immunol. 2003; 33: 962-9.
19. Sambrook J, Russel D. Molecular Cloning: A Laboratory Manual. 3rd edition. Vol. 1. New York, NY, USA: Cold Spring Harbor Laboratory Press; 2001.
20. Nada E., Dalia El-Lebedy, Amira D., Ahmed El-Bastawissy, Alaa Eldin Shalaby. Complement factor H polymorphism rs1061170 and the effect of cigarette smoking on the risk of lung cancer. Contemp Oncol . 2015; 19 (6): 441–445.