Mutlu KARKUCAK, Emel Başkan BÜLBÜL, Hakan TURAN, Tahsin YAKUT, Sevil TOKA, Hayriye SARICAOĞLU

Investigation of Monnose-Binding Lectin gene Polymorphism in Patients with Erythema Multiforme, Stevens-Johnson Syndrome and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Overlap Syndrome

Objective: Monnose-Binding lectin (MBL) appears to play an important role in the immune system. The genetic polymorphisms in the MBL2 gene can result in a reduction of serum levels, leading to a predisposition to recurrent infection. The aim of this study is to investigate the influence of a polymorphism in codon 54 of the MBL2 gene on the susceptibility to Erythema Multiforme, Stevens-Johnson Syndrome and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Overlap Syndrome (EM, SJS and SJS/TEN overlap syndrome). Material and Methods: Our study included 64 patients who were clinically and/or histopathologically diagnosed with EM, SJS, and SJS/TEN overlap syndrome and 66 healthy control subjects who were genotyped for the MBL2 gene codon 54 polymorphism using the PCR-RFLP method. For all statistical analyses, the level of significance was set at p&lt;0.05. Results: The prevalence of the B allele was 18% in the EM, SJS and SJS/TEN patient groups and 13% in the control group. No significant differences in allele frequencies of any polymorphism were observed between the patient and control groups, although the B allele was more frequent in the patient groups (p=0.328). Conclusion: Our results provide no evidence of a relationship between MBL2 gene codon 54 polymorphism and the susceptibility to EM, SJS and SJS/TEN overlap syndrome. However, these findings should be confirmed in studies with a larger sample size. Turkish Anahtar Kelimeler: Polimorfizm, MBL-2 geni, eritema multiforme, Stevens-Johnson Sendromu, Stevens-Johnson Sendromu/Toksik Epidermal Nekroliz Overlap Sendromu Amaç: Mannoz-bağlayıcı-lektin (MBL) immün sistemde önemli bir rol oynamaktadır. MBL-2 genindeki genetik polimorfizmler serum seviyelerinde bir azalmaya neden olarak tekrarlayan enfeksiyonlara yol açabilirler. Bu çalışmanın amacı MBL-2 kodon 54 gen polimorfizminin eritema multiforme, Stevens-Johnson Sendromu ve Stevens-Johnson Sendromu/Toksik Epidermal Nekroliz Overlap Sendromuna (EM, SJS and SJS/TEN overlap sendromu) yatkınlık üzerindeki etkisini araştırmaktır. Gereç ve Yöntemler: Çalışmamıza klinik ve/veya histopatolojik olarak EM, SJS ve SJS/TEN overlap sendromu tanısı almış 64 hasta ve 66 sağlıklı kontrol dahil edildi. Tüm olgulara PCR- RFLP metodu kullanılarak MBL-2 kodon 54 gen polimorfizmi için genotip analizi yapıldı. Tüm istatistiksel analizler için anlamlılık seviyesi p&lt;0,05 olarak belirlendi. Bulgular: B alel prevalansı EM, SJS ve SJS/TEN hasta grubunda %18, kontrol grubunda ise %13 idi. B aleli hasta grubunda daha yüksek sıklıkta saptanmasına rağmen (p=0,328), hasta ve kontrol grupları arasında polimorfizmin alel frekansları açısından anlamlı farklılık saptanmadı. Sonuç: Elde ettiğimiz bulgular MBL-2 kodon 54 gen polimorfizmi ile EM, SJS ve SJS/TEN overlap sendromuna yatkınlık arasında herhangi bir ilişki olmadığını göstermektedir. Ancak, bu sonuçlar daha geniş olgu sayılı çalışmalarla desteklenmelidir.

Keywords:

Polymorphism, MBL2 gene, Erythema multiforme, Stevens-Johnson syndrome, Stevens-Johnson syndrome/toxic epidermal necrolysis overlap syndrome,

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Terai I, Kobayashi K, Matsushita M, Miyakawa H, Mafune N, Ki- kuta H. Relationship between gene polymorphisms of Monnose- binding lectin (MBL) and two molecular forms of MBL. Eur J Im- munol 2003;33:2755-63. [CrossRef]
Dumestre-Perard C, Ponard D, Arlaud GJ, Monnier N, Sim RB, Co- lomb MG. Evaluation and clinical interest of mannan binding lectin function in human plasma. Mol Immunol 2002;39:465-73. [CrossRef]
Fujita T, Matsushita M, Endo Y. The lectin-complement path- way--its role in innate immunity and evolution. Immunol Rev 2004;198:185-202. [CrossRef]
Eisen DP, Minchinton RM. Impact of monnose-binding lectin on suscepti- bility to infectious diseases. Clin Infect Dis 2003;37:1496-505. [CrossRef]
Garred P, Larsen F, Madsen HO, Koch C. Monnose-binding lectin deficiency--revisited. Mol Immunol 2003;40:73-84. [CrossRef]
Forman R, Koren G, Shear NH. Erythema multiforme, Stevens- Johnson syndrome and toxic epidermal necrolysis in children: a re- view of 10 years’ experience. Drug Saf 2002;25:965-72. [CrossRef]
Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC. Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Der- matol 1993;129:92-6. [CrossRef]
French LE, Prins C. Toxic epidermal necrolysis. In:Bolognia JL, Jorizzo JL, Rapini RP, editors. Dermatology St.Louis: Mosby; 2003. 323-31.
Sotozono C, Inagaki K, Fujita A, Koizumi N, Sano Y, Inatomi T, et al. Methicillin-resistant Staphylococcus aureus and methicillin- resistant Staphylococcus epidermidis infections in the cornea. Cornea 2002;21:94-101. [CrossRef]
Vardar F, Pehlivan S, Onay H, Atlihan F, Güliz N, Ozkinay C, et al. Association between mannose binding lectin polymor- phisms and predisposition to bacterial meningitis. Turk J Pediatr 2007;49:270-3.
Roujeau JC, Huynh TN, Bracq C, Guillaume JC, Revuz J, Touraine R. Genetic susceptibility to toxic epidermal necrolysis. Arch Der- matol 1987;123:1171-3. [CrossRef]
Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, et al. Medical genetics: a marker for Stevens- Johnson syndrome. Nature 2004;428:486. [CrossRef]
Ueta M, Sotozono C, Tokunaga K, Yabe T, Kinoshita S. Strong as- sociation between HLA-A*0206 and Stevens-Johnson syndrome in the Japanese. Am J Ophthalmol 2007;143:367- 8. [CrossRef]
Khalil I, Lepage V, Douay C, Morin L, al-Daccak R, Wallach D, et al. HLA DQB1*0301 allele is involved in the susceptibility to erythema multiforme. J Invest Dermatol 1991;97:697-700. [CrossRef]
Léauté-Labrèze C, Lamireau T, Chawki D, Maleville J, Taïeb A. Diagno- sis, classification, and management of erythema multiforme and Ste- vens-Johnson syndrome. Arch Dis Child 2000;83:347-52. [CrossRef]
Di Lernia V, Lo Scocco G, Bisighini G. Erythema multiforme following hepatitis B vaccine. Pediatr Dermatol 1994;11:363-4. [CrossRef]
Griffith RD, Miller OF 3rd. Erythema multiforme following diph- theria and tetanus toxoid vaccination. J Am Acad Dermatol 1988;19:758-9. [CrossRef]
Madsen HO, Garred P, Thiel S, Kurtzhals JA, Lamm LU, Ryder LP, et al. Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein. J Immunol 1995;155:3013-20.
Im CH, Kim J, Lee YJ, Lee EY, Lee EB, Park KS, et al. Monnose- binding lectin 2 gene haplotype analysis in Korean patients with ankylosing spondylitis. Rheumatol Int 2012;32:2251-5. [CrossRef]
Hibberd ML, Sumiya M, Summerfield JA, Booy R, Levin M. As- sociation of variants of the gene for Monnose-binding lectin with susceptibility to meningococcal disease. Meningococcal Re- search Group. Lancet 1999;353:1049-53. [CrossRef]
Lipscombe RJ, Sumiya M, Summerfield JA, Turner MW. Distinct physicochemical characteristics of human mannose binding pro- tein expressed by individuals of differing genotype. Immunology 1995;85:660-7.
Super M, Thiel S, Lu J, Levinsky RJ, Turner MW. Association of low levels of mannan-binding protein with a common defect of opsonisation. Lancet 1989;2:1236-9. [CrossRef]
Seppänen M, Lokki ML, Lappalainen M, Hiltunen-Back E, Rovio AT, Kares S, et al. Monnose-binding lectin 2 gene polymorphism in recurrent herpes simplex virus 2 infection. Hum Immunol 2009;70:218-21. [CrossRef]
Hamvas RM, Johnson M, Vlieger AM, Ling C, Sherriff A, Wade A, et al. Role for mannose binding lectin in the prevention of Myco- plasma infection. Infect Immun 2005;73:5238-40. [CrossRef]
Hashimoto S, Nakamura K, Oyama N, Kaneko F, Fujita T, Tsunemi Y, et al. Monnose-binding lectin (MBL) single nucleotide poly- morphism is not associated with atopic dermatitis in Japanese patients. J Dermatol 2005;32:1038-40.
Aydemir C, Onay H, Oguz SS, Ozdemir TR, Erdeve O, Ozkinay F, et al. Monnose-binding lectin codon 54 gene polymorphism in relation to risk of nosocomial invasive fungal infection in preterm neonates in the neonatal intensive care unit. J Matern Fetal Neo- natal Med 2011;24:1124-7. [CrossRef]
Rantala A, Lajunen T, Juvonen R, Bloigu A, Paldanius M, Silven- noinen-Kassinen S, et al. Low Monnose-binding lectin levels and MBL2 gene polymorphisms associate with Chlamydia pneumoni- ae antibodies. Innate Immun 2011;17:35-40. [CrossRef]
Ueta M, Sotozono C, Inatomi T, Kojima K, Tashiro K, Hamuro J, et al. Toll-like receptor 3 gene polymorphisms in Japanese patients with Ste- vens-Johnson syndrome. Br J Ophthalmol 2007;91:962-5. [CrossRef]
Turan H, Bulbul Baskan E, Yakut T, Karkucak M, Tunali S, Saricao- glu H. Toll-like receptor 9 polymorphism observed with erythema multiforme, stevens johnson syndrome and stevens Johnson syn- drome/toxic epidermal necrolysis overlap syndrome. Bratisl Lek Listy 2011;112; 260-3.