Graves' ophthalmopathy and gene polymorphisms in interleukin‐1α, interleukin‐1β, interleukin‐1 receptor and interleukin‐1 receptor antagonist

Khalilzadeh, Omid; Anvari, Mehdi; Esteghamati, Alireza; Mahmoudi, Mahdi; Tahvildari, Maryam; Rashidi, Armin; Khosravi, Farideh; Amirzargar, Aliakbar

doi:10.1111/j.1442-9071.2009.02093.x

Cited by 29 publications

(32 citation statements)

References 54 publications

(105 reference statements)

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“…Several studies have reported conflicting results regarding the possible role of IL1B -511 C/T polymorphism in AITD. The TT genotype has been described as a protective variant for GD [12], [53], [54], however, other studies did not report any association between this polymorphism and GD or HT [10], [55], [56]. In the present study, we also did not observe a significant association between the IL1B -511 C/T polymorphism and GD or HT.…”

Section: Discussioncontrasting

confidence: 88%

Polymorphisms in the TNFA and IL6 Genes Represent Risk Factors for Autoimmune Thyroid Disease

et al. 2014

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BackgroundAutoimmune thyroid disease (AITD) comprises diseases including Hashimoto's thyroiditis and Graves' disease, both characterized by reactivity to autoantigens causing, respectively, inflammatory destruction and autoimmune stimulation of the thyroid-stimulating hormone receptor. AITD is the most common thyroid disease and the leading form of autoimmune disease in women. Cytokines are key regulators of the immune and inflammatory responses; therefore, genetic variants at cytokine-encoding genes are potential risk factors for AITD.MethodsPolymorphisms in the IL6-174 G/C (rs1800795), TNFA-308 G/A (rs1800629), IL1B-511 C/T (rs16944), and IFNGR1-56 T/C (rs2234711) genes were assessed in a case-control study comprising 420 Hashimoto's thyroiditis patients, 111 Graves' disease patients and 735 unrelated controls from Portugal. Genetic variants were discriminated by real-time PCR using TaqMan SNP genotyping assays.ResultsA significant association was found between the allele A in TNFA-308 G/A and Hashimoto's thyroiditis, both in the dominant (OR = 1.82, CI = 1.37–2.43, p-value = 4.4×10−5) and log-additive (OR = 1.64, CI = 1.28–2.10, p-value = 8.2×10−5) models. The allele C in IL6-174 G/C is also associated with Hashimoto's thyroiditis, however, only retained significance after multiple testing correction in the log-additive model (OR = 1.28, CI = 1.06–1.54, p-value = 8.9×10−3). The group with Graves' disease also registered a higher frequency of the allele A in TNFA-308 G/A compared with controls both in the dominant (OR = 1.85, CI = 1.19–2.87, p-value = 7.0×10−3) and log-additive (OR = 1.69, CI = 1.17–2.44, p-value = 6.6×10−3) models. The risk for Hashimoto's thyroiditis and Graves' disease increases with the number of risk alleles (OR for two risk alleles is, respectively, 2.27 and 2.59).ConclusionsThis study reports significant associations of genetic variants in TNFA and IL6 with the risk for AITD, highlighting the relevance of polymorphisms in inflammation-related genes in the etiopathogenesis of AITD.

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Section: Discussioncontrasting

confidence: 88%

Polymorphisms in the TNFA and IL6 Genes Represent Risk Factors for Autoimmune Thyroid Disease

et al. 2014

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“…IL-1␣ and IL-1␤ are located at the same chromosome band (2q14) as CTLA-4; indeed, associations of these two genes with GD have been described in many studies. A family-based study and a case-control study showed a significant association of IL-1␣ (rs1800587, T-889 C) with GD, whereas Hunt et al failed to do so [15,18,27]. Polymorphism in IL-1␤ (rs16944, A-511 G) has reported their possible role in GD in Asian population, but not with GO.…”

Section: Discussionmentioning

confidence: 88%

“…Several genetic association studies provided suggestive evidence of linkage of GD to the polymorphisms of IL-1␣ and IL-1␤ genes. Two single-nucleotide polymorphisms (SNPs) included in other studies, one located in the 5= flanking region at position Ϫ889 (rs1800587, T-889 C) in the IL-1␣, and the other in the 5= flanking region at position Ϫ511 (rs16944, A-511 G) in the IL-1␤ gene, have been found associated with the risk for GD and GO, but these results are still inconclusive [15][16][17][18].…”

Section: Introductionmentioning

confidence: 96%

The association of interleukin-1α and interleukin-1β polymorphisms with the risk of Graves' disease in a case-control study and meta-analysis

Liu

et al. 2010

Human Immunology

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“…20 We have also shown significant associations between GO and IL-1a and IL-1RA gene polymorphisms in Iranian patients. 24 This study revealed significant associations between GO and certain polymorphisms in INF-g, TNF-a, and IL-12 genes.…”

Section: Discussionmentioning

confidence: 99%

Genetic susceptibility to Graves’ ophthalmopathy: the role of polymorphisms in proinflammatory cytokine genes

Anvari

Khalilzadeh

Esteghamati

et al. 2009

Eye

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Graves' ophthalmopathy and gene polymorphisms in interleukin‐1α, interleukin‐1β, interleukin‐1 receptor and interleukin‐1 receptor antagonist

Abstract: This is the first study to show a positive correlation between polymorphisms in the IL-1alpha and IL-1RA genes and susceptibility to GO. These findings promote further research into genetic correlates of GO.

Cited by 29 publications

References 54 publications

Polymorphisms in the TNFA and IL6 Genes Represent Risk Factors for Autoimmune Thyroid Disease

Polymorphisms in the TNFA and IL6 Genes Represent Risk Factors for Autoimmune Thyroid Disease

The association of interleukin-1α and interleukin-1β polymorphisms with the risk of Graves' disease in a case-control study and meta-analysis

Genetic susceptibility to Graves’ ophthalmopathy: the role of polymorphisms in proinflammatory cytokine genes

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