FNDC5 Geni Polimorfizmleri, Serum İrisin Düzeyleri ve Alerjik Rinit Arasındaki İlişkinin Yokluğu

Amaç: Alerjik rinit (AR), alerjen maruziyetine bağlı olarak tip 1 immünoglobulin E-aracılı reaksiyonlarla oluşan bir enflamatuar burun mukozası hastalığıdır. İrisin, egzersize yanıt olarak iskelet kasları tarafından salınan bir hormondur. İrisin ile inflamasyon ilişkisini gösteren çalışmalar bulunmaktadır. Bu çalışmada, irisin kodlayan fibronektin tip III domain 5 (FNDC5) gen polimorfizmleri, serum irisin seviyeleri ve AR arasındaki potansiyel ilişkiyi araştırmayı amaçladık. Yöntem: Çalışma, 100 AR hastası ve 100 sağlıklı kontrol bireyin yer aldığı bir vaka-kontrol çalışması şeklinde dizayn edilmiştir. FNDC5 geninde bulunan rs726344 ve rs1746661 SNP'lerin genotipleme analizleri PCR-RFLP yöntemiyle gerçekleştirilmiştir. Serum irisin seviyeleri ELISA yöntemi ile ölçülmüştür. Sonuçlar: Hasta grubunda rs726344 SNP genotipleme sonuçlarına göre, %90 GG ve %10 GA genotipleri saptanırken, kontrol grubunda sırasıyla %94 GG ve %6 GA genotipleri belirlendi. AA genotipi hiçbir olguda saptanmadı. rs1746661 SNP için ise hastalarda %57 GG, %39 GT ve %4 TT genotipleri, kontrollerde ise sırasıyla %58 GG, %36 GT ve %6 TT genotipleri saptandı. Hastalar ile kontroller arasında rs726344 ve rs1746661 SNP'lerinde genotipik farklılık saptanmadı. Serum irisin seviyesi, hastalarda 406.3±56.09 ng/ml iken, kontrollerde 354.3±46.06 ng/ml olarak bulundu ve aralarında anlamlı farklılık görülmedi. Sonuç: Bu çalışma, irisin proteininin, kodlayıcı geni ve AR arasındaki ilişkiyi araştırmayı amaçlayan ilk çalışmadır. FNDC5 gen polimorfizmleri, serum irisin seviyeleri ve AR arasında anlamlı bir ilişki saptanmamıştır. Bu bulgular, bu faktörlerin AR gelişiminde sınırlı bir rolünü göstermekle birlikte, irisin-AR ilişkisinin anlaşılması için ileri çalışmalara ihtiyaç bulunmaktadır.

Anahtar Kelimeler:

Alerjik rinit, irisin, FNDC5, SNP, genotipleme.

Lack of Association Between FNDC5 Gene Polymorphisms, Serum Irisin Levels and Allergic Rhinitis

Aim: Allergic rhinitis (AR) is an inflammatory nasal mucosa disease caused by type 1 immunoglobulin E-mediated reactions to allergen exposure. Irisin is a hormone released by skeletal muscles in response to exercise. There are studies that demonstrate the relationship of irisin with inflammation. We aimed to investigate the potential association between irisin coding fibronectin type III domain 5 (FNDC5) gene polymorphisms, serum irisin levels, and AR. Method: A case-control study was designed, involving 100 AR patients and 100 healthy controls. Genotyping of rs726344 and rs1746661 SNPs within the FNDC5 gene was performed using PCR-RFLP method. Serum irisin levels were measured using ELISA. Results: Genotyping of rs726344 SNP in patients revealed 90% GG and 10% GA genotypes, while in controls, it was 94% GG and 6% GA. The AA genotype was not detected in any case. For rs1746661 SNP, patients had 57% GG, 39% GT, and 4% TT genotypes, while controls had 58% GG, 36% GT, and 6% TT genotypes. No significant difference was found in rs726344 and rs1746661 SNPs between the patients and the control group. Serum irisin level was 406.3±56.09 ng/ml in patients and 354.3±46.06 ng/ml in controls with no significant difference. Conclusion: This is the first study aiming to investigate the relationship between the irisin protein, its encoding gene, and AR. No significant association was identified between FNDC5 gene polymorphisms, serum irisin levels, and allergic rhinitis. While these findings suggest a limited role of these factors in AR, further studies are needed for more comprehensive understanding of the irisin-AR relationship.

Keywords:

Allergic rhinitis, irisin, FNDC5, SNP, genotyping,

PDF

___

1. Zhang Y, Lan F, Zhang L. Advances and highlights in allergic rhinitis. Allergy. 2021;76(11):3383-9. DOI: 10.1111/all.15044.
2. Greiner AN, Hellings PW, Rotiroti G, Scadding GK. Allergic rhinitis. Lancet. 2011;378(9809):2112-22. DOI: 10.1016/S0140-6736(11)60130-X.
3. Cingi C, Susaman N, Küçükcan N, Kar M, Altıntaş M, Altın F, et al. The Score for Allergic Rhinitis study in Turkey, 2020. ENT Updates. 2021;11(1):1-7. DOI: 10.5152/entupdates.2021.21024.
4. Chen ML, Zhao H, Huang QP, Xie ZF. Single nucleotide polymorphisms of IL-13 and CD14 genes in allergic rhinitis: a meta-analysis. Eur Arch Otorhinolaryngol. 2018;275(6):1491-500. DOI: 10.1007/s00405-018-4975-7.
5. Amarin JZ, Naffa RG, Suradi HH, Alsaket YM, Obeidat NM, Mahafza TM, et al. An intronic single-nucleotide polymorphism (rs13217795) in FOXO3 is associated with asthma and allergic rhinitis: a case-case-control study. BMC Med Genet. 2017;18(1):132. DOI: 10.1186/s12881-017-0494-4.
6. Li ZP, Yin LL, Wang H, Liu LS. Association between promoter polymorphisms of interleukin-4 gene and allergic rhinitis risk: a meta-analysis. J Huazhong Univ Sci Technolog Med Sci. 2014;34(3):306-13. DOI: 10.1007/s11596-014-1275-3.
7. Yilmaz I, Atac FB, Erkan AN, Verdi H, Cagici CA, Aslan S, et al. No difference in polymorphism frequency in a Turkish population with allergic rhinitis. Acta Otolaryngol. 2006;126(10):1110-1. DOI: 10.1080/00016480600702142.
8. Luo Y, Qiao X, Ma Y, Deng H, Xu CC, Xu L. Disordered metabolism in mice lacking irisin. Sci Rep. 2020;10(1):17368. DOI: 10.1038/s41598-020-74588-7.
9. Pesce M, Ballerini P, Paolucci T, Puca I, Farzaei MH, Patruno A. Irisin and Autophagy: First Update. Int J Mol Sci. 2020;21(20):7587. DOI: 10.3390/ijms21207587.
10. Wei S, Bi J, Yang L, Zhang J, Wan Y, Chen X, et al. Serum irisin levels are decreased in patients with sepsis, and exogenous irisin suppresses ferroptosis in the liver of septic mice. Clin Transl Med. 2020;10(5):e173. DOI: 10.1002/ctm2.173.
11. Chung D, Park KT, Yarlagadda B, Davis EM, Platt M. The significance of serum total immunoglobulin E for in vitro diagnosis of allergic rhinitis. Int Forum Allergy Rhinol. 2014;4(1):56-60. DOI: 10.1002/alr.21240.
12. Bousquet J, Anto JM, Bachert C, Baiardini I, Bosnic-Anticevich S, Walter Canonica G, et al. Allergic rhinitis. Nat Rev Dis Primers. 2020;6(1):95. DOI: 10.1038/s41572-020-00227-0.
13. Bao JF, She QY, Hu PP, Jia N, Li A. Irisin, a fascinating field in our times. Trends Endocrinol Metab. 2022;33(9):601-13. DOI: 10.1016/j.tem.2022.06.003.
14. Badr EA, Mostafa RG, Awad SM, Marwan H, Abd El-Bary HM, Shehab HE, et al. A pilot study on the relation between irisin single-nucleotide polymorphism and risk of myocardial infarction. Biochem Biophys Rep. 2020;22:100742. DOI: 10.1016/j.bbrep.2020.100742.
15. Pavlova T, Zlamal F, Tomandl J, Hodicka Z, Gulati S, Bienertova-Vasku J. Irisin Maternal Plasma and Cord Blood Levels in Mothers with Spontaneous Preterm and Term Delivery. Dis Markers. 2018;2018:7628957. DOI: 10.1155/2018/7628957.
16. Al-Daghri NM, Mohammed AK, Al-Attas OS, Amer OE, Clerici M, Alenad A, et al. SNPs in FNDC5 (irisin) are associated with obesity and modulation of glucose and lipid metabolism in Saudi subjects. Lipids Health Dis. 2016;15:54. DOI: 10.1186/s12944-016-0224-5.
17. Brondani LA, Boelter G, Assmann TS, Leitao CB, Canani LH, Crispim D. Irisin-encoding gene (FNDC5) variant is associated with changes in blood pressure and lipid profile in type 2 diabetic women but not in men. Metabolism. 2015;64(9):952-7. DOI: 10.1016/j.metabol.2015.05.005.
18. Khan DA. Allergic rhinitis and asthma: epidemiology and common pathophysiology. Allergy Asthma Proc. 2014;35(5):357-61. DOI: 10.2500/aap.2014.35.3794.
19. Choi BY, Han M, Kwak JW, Kim TH. Genetics and Epigenetics in Allergic Rhinitis. Genes (Basel). 2021;12(12):2004. DOI: 10.3390/genes12122004.
20. Bulut T, Yalcin AD, Celik B, Genc GE, Gocmen AY, Gumuslu S. Are thermogenic proteins and adipokine chemerin affected by monoclonal antibody therapy in asthma? Eurasian J Pulmonol. 2019;21(3):161-6. DOI: 10.4103/ejop.ejop_60_18.
21. Sun J, Jia X, Duan Y, Zong A. Irisin alleviates lung injury in asthma mice by inhibiting phosphoinositide-3-kinase-protein kinase B (PI3K/AKT) phosphorylation and release of inflammatory factors. Materials Express. 2022;12(7):956-62. DOI: 10.1166/mex.2022.2247.
22. Szilasi ME, Pak K, Kardos L, Varga VE, Seres I, Mikaczo A, et al. The Alteration of Irisin-Brain-Derived Neurotrophic Factor Axis Parallels Severity of Distress Disorder in Bronchial Asthma Patients. Front Neurosci. 2017;11:653. DOI: 10.3389/fnins.2017.00653.
23. Mazur-Bialy AI, Pochec E, Zarawski M. Anti-Inflammatory Properties of Irisin, Mediator of Physical Activity, Are Connected with TLR4/MyD88 Signaling Pathway Activation. Int J Mol Sci. 2017;18(4):701 DOI: 10.3390/ijms18040701.
24. Aldred S, Love JA, Tonks LA, Stephens E, Jones DS, Blannin AK. The effect of steady state exercise on circulating human IgE and IgG in young healthy volunteers with known allergy. J Sci Med Sport. 2010;13(1):16-9. DOI: 10.1016/j.jsams.2008.07.001.
25. Tongtako W, Klaewsongkram J, Jaronsukwimal N, Buranapraditkun S, Mickleborough TD, Suksom D. The effect of acute exhaustive and moderate intensity exercises on nasal cytokine secretion and clinical symptoms in allergic rhinitis patients. Asian Pac J Allergy Immunol. 2012;30(3):185-92. PMID: 23156847.