The objective of this study is to research polymorphisms in MIF ' gene -173 site in variable haemotological malignities and evaluate its effects on febrile neutropenic attacks after chemotherapy in acute leukemia. Single nucleotide polymorphisms (SNPs) at -173 site of the MIF gene was analysed with the PCR-RFLP method (restriction endonudease Alu I) with isolated DNA samples from 48 patients who were treated for ALL and AML and 53 healthy controls, and G and C allel frequencies were compared statistically between patients and healthy controls groups. As a result of the analyzis, it was observed that the rate of patients with GG genotypes was 70.9%, with GC genotypes 29.1%, and with CC genotypes 0%.,Association is evaluated between MIF pozitivities in acute leukemias and distribution of infections, its factors, duration of feveraldays and neutropenia. Within the GC allel group; no significant differences were observed (p>0.05) in infection factors, duration of neutropenia (
1. Denkinger CM, Metz C, Fingerle-Rowson G, Denkinger
MD, Forsthuber T. Macrophage migration inhibitory factor
and its role in autoimmune diseases. Arch Immunol
Ther Ex. 2004;52:389-400
2. Bloom BR, Bennett B. Mechanism of a reaction in
vitro associated with delayed-type hypersensitivity
Science. 1966; 153:80-82
3. Weiser WY, Temple PA, Witek-Giannotti JS, Remold
HG, Clark SC, David JR., et al. Molecular cloning of a
cDNA encoding a human macrophage migration inhibitory
factor. Proc Nat Acad Sci Immunol. 1989;86:7522-7526
4. Paralkar V, Wistow G. Cloning the human gene for
macrophage migration inhibitory factor (MIF). Genomics
1994;19:48-51
5. Zhong XB, Leng L, Beitin A, Chen R, McDonald C,
Hsiao B, et al. Simultaneous detection of microsatellite
repeats and SNPs in the macrophage migration inhibitory
factor gene by thin-film biosensor chips and application
to rural field studies. Nucleic Acid Res. 2005;33,e121
6. Hizawa N, Yamaguchi E, Takahashi D, Nishihira J,
Nishimura M, et al. Functional polymorphisms in the
promoter region of macrophage migration inhibitory
factor and atopy. Am J Respir Crit Care Med
2004;169:1014-1018
7. De Benedetti F, Meazza C, Vivarelli M, Rossi F, Pistorio
A, Lamb R, et al. Functional and prognostic relevance
of the -173 polymorphism of the macrophage migration
inhibitory factor gene in systemic-onset juvenile idiopathic
arthritis. Arthritis Rheu. 2003;48:1398-1407
8. Bernhagen J, Calandra T, Mitchell RA, Martin SB,
Tracey KJ, Voelter W, et al. MIF is a pituitary-derived
cytokine that potentiates lethal endotoxaemia. Nature
1993;365:756-759
9. Bucala R. MIF rediscovered: cytokine, pituitary hormone,
and glucocorticoid-induced regulator of the immune
response. Faseb J. 1996; 10:1607-1613
10. Donn RP, Shelley E, Oilier WER. A novel 5-prime-
flanking region polymorphism of macrophage migration
inhibitory factor is associated with systemic-onset juvenile
idiopathic arthritis. Arthritis Rheum. 2001;44:1782-1785
11. Sambrook JJ, Fritsch EF, and Maniatis T. Molecular
Clonning: A laboratory manual. 1989; 2nd Edition ,Cold
Spring Laboratory Pres, Cold Spring Harbor
12. Bozza FA, Gomes RN, Japiassü AM, Soares M, Castro-
Faria-Neto HC, Bozza PT. et al. Macrophage migration
inhibitory factor levels correlate with fatal outcome in
sepsis. Shock. 2004;22(4):309-13
13. de Mendonça-Filho HT, Gomes GS, Nogueira PM,
Fernandes MA, Tura BR, Santos M, et al. Macrophage
migration inhibitory factor is associated with positive
cultures in patients with sepsis after cardiac surgery
Shock. 2005;24:313-317
14. Afig B, Arif RÖ, Zülal Ü. Association of macrophage
migration inhibitory factor gene -173G/C polymorphism
with prognosis in turkish children with juvenile
rheumatoid arthritis. Rheumatol In. 2005;10:296-305
15. Shun CT, Lin JT, Huang SP, Un MT, Wu MS. Expression
of macrophage migration inhibitory factor is associated
with enhanced angiogenesis and advanced stage in
gastric carcinomas. World J Gastroenterol. 2005; 1: 3767-377
16. Vivarelli M, D'Urbano LE, Stringini G, Ghiggeri GM,
Caridi G, Donn R, et al. Association of the macrophage
migration inhibitory factor -173*C allele with childhood
nephrotic syndrome. Pediatr Nephrol. 2008;23:743-748
17. Rigante D, Flex A, Federico G, Pola R, Candelli M,
Manna R, et al. Serum macrophage migration inhibitory
factor (MIF) in the intercritical phase of hereditary periodic
fevers and its relationship with the MIF-173G/C
polymorphism. Scand J Rheumatol. 2007;36:307-310
18. Awandare GA, Ouma C, Keller CC, Were T, Otieno R, Ouma Y, et al. A macrophage migration inhibitory factor promoter polymorphism is associated with high-density parasitemia in children with malaria. Genes Immun. 2000;7:568-575.
Akut lösemilerde MIF Genindeki polimorfizmlerin önemi ve febril nötropenîk ataklara etkisi
Bu çalışmanın amacı; Akut Lösemiler (AL)'de Makrofaj Migrasyon inhibitor Faktörü (MIF) geninin -173 bölgesine ait polimorfizmleri araştırmak ve kemoterapi sonrası gelişen febril nötropenik (FN) ataklara etkisini değerlendirmektir. Akut Myeloblastik Lösemi (AML) ve Akut Lenfoid Lösemi (ALL) tanısıyla tedavi gören 48 hasta ile 53 sağlıklı kontrolden izole edilen DNA örneklerinde MIF geni -173 bölgesine ait tek nükleotid polimorfizmleri, PCR-RFLP yöntemi ile araştırılarak, G ye C allel ve genotip dağılımları hasta ile kontrol grupları arasında karşılaştırmıştır. Analizler sonucunda GG genotipini taşıyan hastaların oranı %70.9, GC'yi taşıyanların oranı %29.1 ye CC'yi taşıyanların oranı %0 olarak saptanmıştır. Hasta ve kontrol grubunda genotip ye allel frekansları açısından anlamlı bir farklılık ile Hardy-Weinberg dengesinden bir sapma gözlenmemiştir. AL'lerde elde edilen MIF pozitifliği ile infeksiyonların dağılımı,'etkenleri, ateşli gün süresi ve nötropeni süresi arasındaki ilişki değerlendirildiğinde; GC allel grubunda, infeksiyonların etkenleri, nötropeni (0.05). Sonuç olarak; Fungal - pnömoni, GC aleli taşıyan grupta, GG aleli taşıyan gruba göre (%22/ll,5) daha sık izlenmiş olup çalışma grubunun' genişletilerek tekrarlanması durumunda anlamlı bir ilişki saptanabileceği düşünülmüştür.
1. Denkinger CM, Metz C, Fingerle-Rowson G, Denkinger
MD, Forsthuber T. Macrophage migration inhibitory factor
and its role in autoimmune diseases. Arch Immunol
Ther Ex. 2004;52:389-400
2. Bloom BR, Bennett B. Mechanism of a reaction in
vitro associated with delayed-type hypersensitivity
Science. 1966; 153:80-82
3. Weiser WY, Temple PA, Witek-Giannotti JS, Remold
HG, Clark SC, David JR., et al. Molecular cloning of a
cDNA encoding a human macrophage migration inhibitory
factor. Proc Nat Acad Sci Immunol. 1989;86:7522-7526
4. Paralkar V, Wistow G. Cloning the human gene for
macrophage migration inhibitory factor (MIF). Genomics
1994;19:48-51
5. Zhong XB, Leng L, Beitin A, Chen R, McDonald C,
Hsiao B, et al. Simultaneous detection of microsatellite
repeats and SNPs in the macrophage migration inhibitory
factor gene by thin-film biosensor chips and application
to rural field studies. Nucleic Acid Res. 2005;33,e121
6. Hizawa N, Yamaguchi E, Takahashi D, Nishihira J,
Nishimura M, et al. Functional polymorphisms in the
promoter region of macrophage migration inhibitory
factor and atopy. Am J Respir Crit Care Med
2004;169:1014-1018
7. De Benedetti F, Meazza C, Vivarelli M, Rossi F, Pistorio
A, Lamb R, et al. Functional and prognostic relevance
of the -173 polymorphism of the macrophage migration
inhibitory factor gene in systemic-onset juvenile idiopathic
arthritis. Arthritis Rheu. 2003;48:1398-1407
8. Bernhagen J, Calandra T, Mitchell RA, Martin SB,
Tracey KJ, Voelter W, et al. MIF is a pituitary-derived
cytokine that potentiates lethal endotoxaemia. Nature
1993;365:756-759
9. Bucala R. MIF rediscovered: cytokine, pituitary hormone,
and glucocorticoid-induced regulator of the immune
response. Faseb J. 1996; 10:1607-1613
10. Donn RP, Shelley E, Oilier WER. A novel 5-prime-
flanking region polymorphism of macrophage migration
inhibitory factor is associated with systemic-onset juvenile
idiopathic arthritis. Arthritis Rheum. 2001;44:1782-1785
11. Sambrook JJ, Fritsch EF, and Maniatis T. Molecular
Clonning: A laboratory manual. 1989; 2nd Edition ,Cold
Spring Laboratory Pres, Cold Spring Harbor
12. Bozza FA, Gomes RN, Japiassü AM, Soares M, Castro-
Faria-Neto HC, Bozza PT. et al. Macrophage migration
inhibitory factor levels correlate with fatal outcome in
sepsis. Shock. 2004;22(4):309-13
13. de Mendonça-Filho HT, Gomes GS, Nogueira PM,
Fernandes MA, Tura BR, Santos M, et al. Macrophage
migration inhibitory factor is associated with positive
cultures in patients with sepsis after cardiac surgery
Shock. 2005;24:313-317
14. Afig B, Arif RÖ, Zülal Ü. Association of macrophage
migration inhibitory factor gene -173G/C polymorphism
with prognosis in turkish children with juvenile
rheumatoid arthritis. Rheumatol In. 2005;10:296-305
15. Shun CT, Lin JT, Huang SP, Un MT, Wu MS. Expression
of macrophage migration inhibitory factor is associated
with enhanced angiogenesis and advanced stage in
gastric carcinomas. World J Gastroenterol. 2005; 1: 3767-377
16. Vivarelli M, D'Urbano LE, Stringini G, Ghiggeri GM,
Caridi G, Donn R, et al. Association of the macrophage
migration inhibitory factor -173*C allele with childhood
nephrotic syndrome. Pediatr Nephrol. 2008;23:743-748
17. Rigante D, Flex A, Federico G, Pola R, Candelli M,
Manna R, et al. Serum macrophage migration inhibitory
factor (MIF) in the intercritical phase of hereditary periodic
fevers and its relationship with the MIF-173G/C
polymorphism. Scand J Rheumatol. 2007;36:307-310
18. Awandare GA, Ouma C, Keller CC, Were T, Otieno R, Ouma Y, et al. A macrophage migration inhibitory factor promoter polymorphism is associated with high-density parasitemia in children with malaria. Genes Immun. 2000;7:568-575.
Güven, S., Pehlivan, M., Yılmaz, M., Okan, V., et al. (2009). Akut lösemilerde MIF Genindeki polimorfizmlerin önemi ve febril nötropenîk ataklara etkisi. Gaziantep Medical Journal, 15(2), 5-9.
AMA
Güven S, Pehlivan M, Yılmaz M, Okan V, Pehlivan S. Akut lösemilerde MIF Genindeki polimorfizmlerin önemi ve febril nötropenîk ataklara etkisi. Gaziantep Medical Journal. March 2009;15(2):5-9.
Chicago
Güven, Sebahat, Mustafa Pehlivan, Mehmet Yılmaz, Vahap Okan, and Sacide Pehlivan. “Akut lösemilerde MIF Genindeki Polimorfizmlerin önemi Ve Febril nötropenîk Ataklara Etkisi”. Gaziantep Medical Journal 15, no. 2 (March 2009): 5-9.
EndNote
Güven S, Pehlivan M, Yılmaz M, Okan V, Pehlivan S (March 1, 2009) Akut lösemilerde MIF Genindeki polimorfizmlerin önemi ve febril nötropenîk ataklara etkisi. Gaziantep Medical Journal 15 2 5–9.
IEEE
S. Güven, M. Pehlivan, M. Yılmaz, V. Okan, and S. Pehlivan, “Akut lösemilerde MIF Genindeki polimorfizmlerin önemi ve febril nötropenîk ataklara etkisi”, Gaziantep Medical Journal, vol. 15, no. 2, pp. 5–9, 2009.
ISNAD
Güven, Sebahat et al. “Akut lösemilerde MIF Genindeki Polimorfizmlerin önemi Ve Febril nötropenîk Ataklara Etkisi”. Gaziantep Medical Journal 15/2 (March 2009), 5-9.
JAMA
Güven S, Pehlivan M, Yılmaz M, Okan V, Pehlivan S. Akut lösemilerde MIF Genindeki polimorfizmlerin önemi ve febril nötropenîk ataklara etkisi. Gaziantep Medical Journal. 2009;15:5–9.
MLA
Güven, Sebahat et al. “Akut lösemilerde MIF Genindeki Polimorfizmlerin önemi Ve Febril nötropenîk Ataklara Etkisi”. Gaziantep Medical Journal, vol. 15, no. 2, 2009, pp. 5-9.
Vancouver
Güven S, Pehlivan M, Yılmaz M, Okan V, Pehlivan S. Akut lösemilerde MIF Genindeki polimorfizmlerin önemi ve febril nötropenîk ataklara etkisi. Gaziantep Medical Journal. 2009;15(2):5-9.