Association of<i>Interleukin-1B</i>and<i>Interleukin-4</i>Gene Variants with Autoimmune Thyroid Diseases in Tunisian Population

Zaaber, Ines; Mestiri, Souhir; Hammedi, Hounayda; Marmouch, H.; Mahjoub, S.; Jrad, Besma Bel Hadj; Saïd, Khaled

doi:10.3109/08820139.2016.1153650

Cited by 18 publications

(17 citation statements)

References 37 publications

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“…The pro-inflammatory effect of IL-1β is based on bone resorption by activation of osteoclasts and encouraged RANKL expression. 35,36 This study showed a statistically significant positive linear relationship between age, anti-dsDNA, anti-CCP, RF and duration of thyroiditis with the occurrence of rheumatic diseases, with anti-dsDNA and RF being the most significant predictors. A recent study on hypothyroid/euthyroid postmenopausal women disclosed that TSH positively correlated with OPG and negatively with IL-6 and osteocalcin, moreover that thyroid autoimmunity can affect OPG/RANKL levels independently of hypothyroidism.…”

Section: Discussionmentioning

confidence: 55%

The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in postmenopausal women

Polovina

Miljić

Zivojinović³

et al. 2017

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ObJeCTIVe: Skeletal development, linear growth, cartilage biology and bone turnover are highly dependent on the activity of thyroid hormones. Thyroid dysfunction affects the skeleton, and autoimmune thyroid disease, manifesting as a chronic inflammatory condition, may be an important contributing factor to impaired bone quality in these patients. MATeRIAlS AND MeTHODS: Measurement of TSH, FT4, TPOAb and bone mineral density and FRAX score calculations were performed in 189 postmenopausal women (110 euthyroid women and 79 women diagnosed with subclinical hypothyroidism) divided into subgroups according to the presence of TPOAb. ReSUlTS: In multivariate logistic regression analysis only TPOAb were found to be significantly related to fracture, independently of TSH values (p=0.018; OR=7.800; 95% CI 1.424-42.721). Lower bone mineral density and FRAX score for hip and for major osteoporotic fractures were associated with the presence of TPOAb in euthyroid postmenopausal women in an unadjusted logistic regression model, as well as in a model adjusted for age, bMI and smoking. TSH was a better predictive factor for fractures in women with subclinical hypothyroidism (FRAX main p <0.001; 95% CI for SE 0.858-0.959 and FRAX hip p <0.001; 95% CI for SE 0.628-0.854). CONCLUSION: Autoimmune thyroid disease is associated with decreased bone mineral density at both spine and hip and risk of future fracture incidence in euthyroid postmenopausal women. Presence of TPOAb is a potential marker of higher fracture risk in these patients. However, in subclinical hypothyroidism, TSH is a better indicator of future fragility fractures than TPOAb.

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Section: Discussionmentioning

confidence: 55%

The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in postmenopausal women

Polovina

Miljić

Zivojinović³

et al. 2017

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“…IL‐1β is a protein known by its crucial pathophysiological role in inflammatory disorders and its influence in silicosis susceptibility and/or severity has been investigated in several animal model studies, and in a clinical study . We hypothesized that there is a possible association of the IL1B +3954C>T polymorphism with the severity of silicosis, since this polymorphism has been previously associated with the severity and susceptibility to several inflammatory diseases . However, no association of the IL1B +3954C>T polymorphism with silicosis severity was detected (simple or complicated silicosis) in the present work.…”

Section: Discussionmentioning

confidence: 97%

“…Buccal cell samples were obtained by mouthwash with 5 mL of saline solution for 60 seconds, identified, and immediately stored in a freezer at −4°C. The genomic DNA extraction was performed directly from saliva by the method described by AIDAR and LINE …”

Section: Methodsmentioning

confidence: 99%

“…First, the +3954C/T (rs1143634) is located in exon 5 of the IL1B gene and the T variant allele is associated with a diminished protein expression compared to the ancestral C allele . Besides silicosis, this polymorphism has been previously associated with the modulation of the severity of other inflammatory diseases, such as Hashimoto's thyroiditis, Graves’ disease, periodontitis, and rheumatoid arthritis . Second, the −889C/T (rs1800587) SNP is located in the 5′‐untranslated region (5′‐UTR) of the IL1A gene and plays an important role in the transcriptional regulation of the gene, leading to an increased serum protein level .…”

Section: Introductionmentioning

confidence: 99%

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Interleukin 1α and 1β gene variations are associated with tuberculosis in silica exposed subjects

Salum

Castro

Moreira

et al. 2019

American J Industrial Med

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Introduction: Silicosis is a fibrotic lung disease resulting from the inhalation of crystalline silica and can be classified as simple or complicated according to the International Labour Organization criteria. Furthermore, individuals exposed to crystalline silica also have a higher risk for the development of tuberculosis (Tb).The contribution of inflammatory cytokines to the risk of silicosis and Tb in different populations has previously been reported. Since genetic background might be related to susceptibility to silicosis and Tb, the study of polymorphisms within IL-1α, IL-1β, and tumor necrosis factor protein-coding genes may contribute to elucidating the genetic basis of these diseases.Methods: Single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction using restriction fragment length polymorphism or by Taqman methodology, in a sample of 102 silica-exposed patients from Brazil.Results: No significant associations were observed between the SNPs studied and the severity of silicosis. However, significant associations were found between Tb and the C allele (odds ratio [OR] = 1.93, 95% confidence interval [CI], 1.01-3.73) and the CC genotype (OR = 2.34, 95% CI, 1.04-5.31) of IL1A −899C>T. The IL1B +3954C>T polymorphism also showed an association with Tb (T allele dominant model OR = 2.38, 95% CI, 1.04-5.41). Conclusion:These preliminary results demonstrate that the IL1A and IL1B gene variations may contribute to some extent to susceptibility to Tb, but not silicosis.However, additional studies are still needed to confirm these results.

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“…In a previous study, we showed also the implication of IL‐4 polymorphism in HT. We found an association between a variable number of tandem repeat (VNTR) polymorphism in intron 3 of the IL‐4 gene and HT susceptibility (Zaaber et al, ). Our results are in line with the study of Hunt and collaborators who showed an association between IL‐4 rs2243250 polymorphism and HT (Hunt et al, ).…”

Section: Discussionmentioning

confidence: 99%

Association of cytokine Th2 gene polymorphisms with autoimmune thyroid diseases in Tunisian population

Mestiri

Zaaber

Inoubli

et al. 2020

Int J Immunogenetics

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Autoimmune thyroid diseases (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are complex genetic diseases. Th2 cytokines act on the development of AITD. This study was conducted on Tunisian patients with AITD to investigate the association of Th2 cytokine gene polymorphisms and haplotype combination with GD or HT risk. A total of 156 controls, 160 patients with HT and 88 patients with GD were genotyped for IL-4 rs2243250, IL-5 rs2069812, IL-6 rs1800796 and IL-13 rs1800925 polymorphisms by PCR-RFLP. The AITD risk was assessed by a logistic regression analysis using the SNP stats statistical program. False-positive report probability (FPRP) was estimated to evaluate significant findings. IL-13 rs1800925 was associated with GD, after adjustment for age and gender, in codominant, dominant and allele genetic models (p = .0072; p = .0018; p = .012, respectively). Significant association of the IL-6 rs1800796C/G genotype with GD was also detected (p = .025).Furthermore, increased risk of HT was still found for IL-13 rs1800925T allele (p = .039, OR = 1.39) and for IL-4 rs2243250T/T genotype both in codominant (p = .033, OR = 2.59) and recessive (p = .011, OR = 2.73) models after adjustment for age and gender. Interestingly, haplotype analysis performed on the IL-4, IL-5 and IL-13 genes revealed a high risk of HT with CTT haplotype (p = .008, OR = 2.12). However, the CCT haplotype is a protective factor (OR = 0.36). Patients carrying the CT haplotype with only one minor allele had a moderate risk of HT (OR = 1.56). The FPRP analysis showed that the association of IL-13 rs1800925 polymorphism with GD and HT and the association of CTT haplotype with HT were noteworthy. In conclusion, the IL-4, IL-5, IL-6 and IL-13 polymorphism may play a role in susceptibility to GD and HT in the Tunisian population. Furthermore, gene-gene interaction between the IL-4, IL-5 and IL-13 significantly increases the risk of AITD. Further studies with larger numbers of individuals are needed to confirm the results. K E Y W O R D Sautoimmune thyroid diseases, IL-13, IL-4, IL-5, IL-6, polymorphism | 295 MESTIRI ET al.

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Association ofInterleukin-1BandInterleukin-4Gene Variants with Autoimmune Thyroid Diseases in Tunisian Population

Cited by 18 publications

References 37 publications

The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in postmenopausal women

The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in postmenopausal women

Interleukin 1α and 1β gene variations are associated with tuberculosis in silica exposed subjects

Association of cytokine Th2 gene polymorphisms with autoimmune thyroid diseases in Tunisian population

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