Interleukin-1 gene variants and the risk of non-syndromic microtia

Abstract

INTRODUCTION: Microtia is a congenital anomaly, manifested by a small and disfigured auricle. Interleukin (IL) 1 is an important mediator of inflammation and cartilage destruction, This study is aimed at investigating association of IL-1A (-889) and IL-1B (-511) variants in a Turkish patient population with microtia.
METHODS: Nineteen patients diagnosed with microtia and 40 healthy controls were enrolled to the study. The IL-1A (-889) and IL-1B (-511) variants were evaluated using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. For statistical analysis, SPSS version 22.0 was used.
RESULTS: The genotype distribution of the IL-1A (-889) variant was statistically different between the cases and the control group. IL-1A -889 CC genotype was lower in microtia cases while TT genotype was more prevalent in microtia cases, respectively (p=0.008, p=0.008). High difference was also observed when the patient group and the control group were compared according to IL-1 (-889) CT+TT (p=0.003). IL-1A (-889) C allele was lower in microtia patients and T allele was higher in patients (p=0.005). The allele frequency and genotype distribution of IL-1B (-511) CT variant did not show any statistically difference between patients and controls (p>0.05).
DISCUSSION AND CONCLUSION: To our knowledge, for the first time in the literature we have demonstrated a significant association of the IL-1A (-889) functional variant with microtia in a Turkish cohort.

İngilizce Kısa Başlık: IL-1 gene variants in microtia

Keywords

• Microtia,interleukin-1A,interleukin-1B,variant

İnterlökin 1 gen varyantları ve sendromik olmayan mikrotia riski

Öz

GİRİŞ ve AMAÇ: Mikrotia küçük ve şekil bozukluğu olan kulak kepçesi ile görülen kongenital bir anomalidir. İnterlökin (IL) 1 enflamasyon ve kıkırdak harabiyeti için önemli bir düzenleyicidir. Bu çalışma Türk mikrotia hastalarında IL-1A (-889) ve IL-1B (-511) varyantlarının ilişkisini değerlendirmeyi amaçlamıştır.
YÖNTEM ve GEREÇLER: Çalışmaya mikrotia tanılı 19 hasta ve 40 sağlıklı kontrol dahil edilmiştir. IL-1A (-889) ve IL-1B (-511) varyantları polimeraz zincir reaksiyonu (PZR)- sınırlayıcı parça uzunluk polimorfizm (RFLP) yöntemi ile incelenmiştir. İstatistik analiz için, SPSS 22.0 versiyonu kullanılmıştır.
BULGULAR: IL-1A (-889) varyant genotip dağılımı hastalar ve kontrol grubu arasında istatistiksel olarak farklıydı. IL-1A -889 TT genotipi mikrotia hastalarında daha yaygınken, CC genotipi mikrotia hastalarında daha azdı, sırasıyla (p=0.008, p=0.008). Hasta ve kontrol grupları IL-1 (-889) CT+TT durumuna göre karşılaştırıldığında büyük fark saptandı (p=0.003). IL-1A (-889) C alleli mikrotia hastalarında azdı ve T alleli hastalarda çoktu (p=0.005). IL-1B (-511) CT varyant genotip ve allel dağılımı hastalar ve kontrol arasında herhangi istatistiksel fark göstermedi (p>0.05).

TARTIŞMA ve SONUÇ: Bildiğimiz kadarıyla literatürde ilk olarak, IL-1A (-889) fonksiyonel varyantın Türk topluluğunda mikrotia ile önemli ilişkisi olduğunu gösterdik.

Türkçe Kısa Başlık: Mikrotiada IL-1 gen varyantları

Anahtar Kelimeler

• Microtia,interlökin-1A,interlökin-1B,varyant

References

1. 1. Luquetti DV, Heike CL, Hing AV, Cunningham ML, Cox TC. Microtia: Epidemiology and genetics. Am J Med Genet A 2012;158A:124-39.
2. 2. Cremers CW. Meatal atresia and hearing loss. Autosomal dominant and autosomal recessive inheritance. Int J Pediatr Otorhinolaryngol 1985;8:211-213.
3. 3. Vishnoi M, Pandey SN, Choudhuri G, Mittal B. IL-1 gene polymorphisms and genetic susceptibility of gallbladder cancer in a north Indian population. Cancer Genet Cytogenet 2008;186:63-68.
4. 4. Kruessel JS, Huang HY, Wen Y, Kloodt AR, Bielfeld P, Polan ML. Different pattern of interleukin-1 beta-(IL-1 beta), interleukin-1 receptor antagonist- (IL-1ra) and interleukin-1 receptor type I- (IL-1R tI) mRNA-expression in single preimplantation mouse embryos at various developmental stages. J Reprod Immunol 1997;34(2):103-120.
5. 5. Cortial D, Gouttenoire J, Rousseau CF, et al. Activation by IL-1 of bovine articular chondrocytes in culture within a 3D collagen-based scaffold. An in vitro model to address the effect of compounds with therapeutic potential in osteoarthritis. Osteoarthritis Cartilage 2006;14:631-640.
6. 6. Haroon J, Hussain S, Javed Q. Heritability of IL-1A Gene Promoter Polymorphism in Patients With Coronary Artery Disease: A Trio-Family Study. Lab Med 2015;46:20-25.
7. 7. di Giovine FS, Takhsh E, Blakemore AI, Duff GW. Single base polymorphism at -511 in the human interleukin-1 beta gene (IL1 beta). Hum Mol Genet 1992;1:450.
8. 8. Achyut BR, Srivastava A, Bhattacharya S, Mittal B. Genetic association of interleukin-1beta (-511C/T) and interleukin-1 receptor antagonist (86 bp repeat) polymorphisms with Type 2 diabetes mellitus in North Indians. Clin Chim Acta 2007;377:163-169.

9. 9. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.
10. 10. Maria de Freitas, N Imbronito AV, Neves AC, Nunes FD, Pustiglioni FE, Lotufo RF. Analysis of IL-1A(-889) and TNFA(-308) gene polymorphism in Brazilian patients with generalized aggressive periodontitis. Eur Cytokine Netw 2007;18:142-147.
11. 11. Bioque G, Crusius JB, Koutroubakis I, et al. Allelic polymorphism in IL-1 beta and IL-1 receptor antagonist (IL-1Ra) genes in inflammatory bowel disease. Clin Exp Immunol 1995;102:379-383.
12. 12. http://ihg2.helmholtz-muenchen.de/cgi-bin/hw/hwa1.pl.(Accessed July 29,2017)
13. 13. Forrester MB, Merz RD. Descriptive epidemiology of anotia and microtia, Hawaii, 1986-2002. Congenit Anom (Kyoto) 2005;45:119-124.
14. 14. Alasti F, Van Camp G. Genetics of microtia and associated syndromes. J Med Genet 2009;46:361-369.
15. 15. Singh M, Chaudhry P, Asselin E. Bridging endometrial receptivity and implantation: network of hormones, cytokines, and growth factors. J Endocrinol 2011;210:5-14.
16. 16. Kauma S, Matt D, Strom S, Eierman D, Turner T. Interleukin-lp (IL-lb),human leukocyte antigen HLA-DRn, and transforming growth factor-b (TGF-b) expression in endometrium, placenta and placental membranes. Am J Obstet Gynecol 1990;163:1430-1437.
17. 17. Orsi NM. Cytokine networks in the establishment and maintenance of pregnancy. Hum Fertil (Camb) 2008;11:222-230.
18. 18. Goldring MB, Birkhead JR, Sandell LJ, Kimura T, Krane SM. Interleukin 1 suppresses expression of cartilage-specific types II and IX collagens and increases types I and III collagens in human chondrocytes. J Clin Invest 1988;82:2026-2037.
19. 19. Richardson DW, Dodge GR. Effects of interleukin-1β and tumor necrosis factor-α on expression of matrix-related genes by cultured equine articular chondrocytes. Am J Vet Res 2000;61:624-630.
20. 20. Henrotin YE, DeGroove DD, Labasse AH, et al. Effects of exogenous IL-1, TNF-α, IL-6, IL-8 and LIF on cytokine production by human articular chondrocytes. Osteoarthritis Cartilage 1996;4:163-173.
21. 21. Arner EC, Pratta MA. Modulation of interleukin-1-induced alterations in cartilage proteoglycan metabolism by activation of protein kinase C. Arthritis Rheum 1991;34:1006-1013.
22. 22. Ghasemi M, Kashani E, Fayyaz A, Attar M, Shahbazi M. Interleukin-1 alpha variation is associated with the risk of developing preeclampsia. Eur J Obstet Gynecol Reprod Biol 2015;193:75-78.
23. 23. Sun X, Cai H, Li Z, et al. Association between IL-1β polymorphisms and gastritis risk: A meta-analysis. Medicine (Baltimore) 2017;96:e6001.