The Allele 2 of the VNTR Polymorphism in the Gene That Encodes a Natural Inhibitor of IL-1β, IL-1RA Is Favorably Associated With Chronic Otitis Media

Živković, Maja; Kolić, Ivana; Jesić, S; Jotić, Ana; Stanković, Aleksandra

doi:10.21053/ceo.2017.01060

Cited by 7 publications

(4 citation statements)

References 33 publications

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“…According to some studies the carriers of IL-1RN *2 have higher IL-1RA levels (53,55,56), and consequently the 2 allele effects could down-regulate IL-1 mediated pro-inflammatory signaling pathways by the IL-1RA blocking of IL-1R1 (37,57,58). A recent study (59) showed that individuals with genotype 2/2 VNTR IL-1RN exhibited higher IL-1RA expression compared to 1/2 and 1/1 genotypes.…”

Section: Il-1rn Vntr Polymorphismmentioning

confidence: 99%

Interleukin 1 receptor antagonist gene variable number of tandem repeats polymorphism and cutaneous melanoma

et al. 2019

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Immunity and cytokines serve crucial roles in cutaneous melanoma. The present study investigated whether a variable number tandem repeat (VNTR) polymorphism of interleukin-1 receptor antagonist (IL-1RA) gene (IL-1RN) located in intron 2 (rs2234663) is associated with cutaneous melanoma. A total of 515 subjects were studied, 133 of which were cutaneous melanoma cases (72 stage I+II non-metastatic melanoma cases and 61 stage III+IV metastatic melanoma cases), and 382 subjects were matching healthy controls from the Friuli-Venezia-Giulia Region located in Northeast Italy, an area with a high melanoma incidence. The IL-1RN-VNTR polymorphism was determined by DNA fragment length analysis following PCR amplification. According to the number of 86-bp repeats, five different IL-1RN alleles were identified: Allele 1 (4-repeats), allele 2 (2-repeats, short allele), allele 3 (5-repeats), allele 4 (3-repeats) and allele 5 (6-repeats). Alleles with three or more 86-bp repeats, i.e. allele 1, 3, 4 and 5 were collectively denoted as long (L) repeats. The present study revealed that IL-1RN-VNTR 1/2 and 2/L genotypes were more frequent among patients with cutaneous melanoma (43.6 and 45.1%, respectively) compared with healthy controls [29.6 and 30.6%, respectively; odds ratio (OR), 1.84; CI, 1.22-2.77; P=0.003; and OR, 1.66; CI, 1.24-2.79; P=0.002, respectively]. Conversely, the IL-1RN-VNTR 1/1 genotype was less frequent among melanoma cases (45.9%) compared with healthy controls (57.9%; OR, 0.62; CI, 0.41-0.92; P=0.017). Comparison of metastatic vs. non-metastatic melanoma cases identified no significant differences. The present study first demonstrated that carriage of the 1/1 IL-1RN-VNTR genotype was protective, whereas 1/2 and 2/L was a risk factor for patients with cutaneous melanoma vs. healthy controls. The short allele 2 was associated with higher expression levels of IL-1RA, a potent competitive inhibitor of the proinflammatory cytokines IL-1α and IL-1β. VNTR-IL-1RN polymorphism may affect susceptibility to melanoma and, thus, it is a potential novel diagnostic biomarker for melanoma. The present study increased the understanding of genetic melanoma susceptibility/carcinogenesis, and may indicate novel strategies in the personalized prevention of cutaneous melanoma.

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Section: Il-1rn Vntr Polymorphismmentioning

confidence: 99%

Interleukin 1 receptor antagonist gene variable number of tandem repeats polymorphism and cutaneous melanoma

et al. 2019

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“…Deubiquitinase cylindromatosis (CYLD) has been found to suppress NTHi-induced inflammation by inhibiting the expression of the key pro-inflammatory chemokine IL-8 via the MAP kinase phosphatase 1 (MKP-1)dependent inhibition of extracellular signal-regulated kinase (ERK) (Wang et al, 2014b). In a recent study, Zivkovic et al found that the IL-1RA VNTR allele 2 was associated with a chronic OM patient in Serbia and suggested that the allele is associated with higher IL-1RA levels, consistent with the increase in IL-1RA observed in mouse models of OM (Zivkovic et al, 2018).…”

Section: Genes Involved In Anti-inflammatory Responses In Ommentioning

confidence: 81%

Current Understanding of Host Genetics of Otitis Media

Geng¹,

Wang²,

Chen³

et al. 2020

Front. Genet.

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The pathogenesis of otitis media (OM), an inflammatory disease of the middle ear (ME), involves interplay between many different factors, including the pathogenicity of infectious pathogens, host immunological status, environmental factors, and genetic predisposition, which is known to be a key determinant of OM susceptibility. Animal models and human genetics studies have identified many genes and gene variants associated with OM susceptibility: genes that encode components of multiple signaling pathways involved in host immunity and inflammatory responses of the ME mucosa; genes involved in cellular function, such as mucociliary transport, mucin production, and mucous cell metaplasia; and genes that are essential for Eustachian tube (ET) development, ME cavitation, and homeostasis. Since our last review, several new mouse models with mutations in genes such as CCL3, IL-17A, and Nisch have been reported. Moreover, genetic variants and polymorphisms in several genes, including FNDC1, FUT2, A2ML1, TGIF1, CD44, and IL1-RA variable number tandem repeat (VNTR) allele 2, have been identified as being significantly associated with OM. In this review, we focus on the current understanding of the role of host genetics in OM, including recent discoveries and future research prospects. Further studies on the genes identified thus far and the discovery of new genes using advanced technologies such as gene editing, next generation sequencing, and genome-wide association studies, will advance our understanding of the molecular mechanism underlying the pathogenesis of OM and provide new avenues for early screening and developing effective preventative and therapeutic strategies to treat OM.

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“…It has an influence on numerous target cells, stimulating the pro-inflammatory network in the middle ear. Hence, it could result in the activation and proliferation of fibroblasts and the growth of osteoclasts in the middle ear, possibly leading to fibrosis and bone erosion 30 …”

Section: Discussionmentioning

confidence: 99%

Audiometric notch for the prediction of early occupational hearing loss and its association with the interleukin-1beta genotype

Amer

Taha

Ibrahim

et al. 2019

Journal of Taibah University Medical Sciences

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Objectives Noise-induced hearing loss (NIHL) is a frequent and irreversible industrial-health problem, the early diagnosis of which can prevent hearing deterioration, especially of speech frequencies. This study aimed to assess hearing impairment in workers occupationally exposed to noise. Audiometric notches and IL-1β gene polymorphisms were evaluated. Methods The study included 98 workers employed in a textile factory. Pure-tone audiometric testing was conducted for all workers, using a manual pure-tone diagnostic audiometer, and the noise level was measured at four different work sites in a spinning section. IL-1β gene polymorphism was determined using PCR-RFLP methods. Results Workers were exposed to a mean noise level of 105.5 dB. As many as 27.6% of them complained of tinnitus and the majority suffered from some degree of hearing loss in either ear, but none of them exceeded 60 dB. Audiometric notches were detected in either one or both ears. Only 28.6% of workers showed the absence of notches. The TT genotype of IL-1β polymorphisms was dominant in 49% of the workers, whereas TC was predominant in 39.8% and CC in 11.2%. The CC genotype was associated with smoking (54.5%) and audiometric notches (100%). The IL-1β genotype distribution showed no significant difference with or without tinnitus. Conclusion This study showed an association between the CC genotype and smoking as well as audiometric notches in workers occupationally exposed to noise. Workers showing audiometric notches should be followed up regularly. Further studies are required to confirm the interrelationship amongst tinnitus, audiometric notches, and IL-1β genotypes.

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The Allele 2 of the VNTR Polymorphism in the Gene That Encodes a Natural Inhibitor of IL-1β, IL-1RA Is Favorably Associated With Chronic Otitis Media

Cited by 7 publications

References 33 publications

Interleukin 1 receptor antagonist gene variable number of tandem repeats polymorphism and cutaneous melanoma

Interleukin 1 receptor antagonist gene variable number of tandem repeats polymorphism and cutaneous melanoma

Current Understanding of Host Genetics of Otitis Media

Audiometric notch for the prediction of early occupational hearing loss and its association with the interleukin-1beta genotype

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