Association of Cytokine Gene Polymorphisms (IL6, IL10, TNF-&amp;#945;, TGF-&amp;#946; and IFN-&amp;#947;) and Graves’ Disease in Turkish Population

Kutlutürk, Faruk; Yarman, Sema; Sarvan, Fatma Oguz; Kekik, Çiğdem

doi:10.2174/18715303113139990001

Cited by 14 publications

(10 citation statements)

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“…This result is consistent with the lack of association with GD in a Polish [8] and Taiwanese populations [11]. In contrast, two other studies in an Iranian [15] and Turkish [27] populations reported association of the IL6 -174 SNP with GD, albeit in the latter the association was on the threshold of significance. To the best of our knowledge, there are no reports implying the IL6 -174 G/C polymorphism in HT susceptibility.…”

Section: Discussionsupporting

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: Discussionsupporting

confidence: 88%

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

et al. 2014

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“…Earlier published reports and present study indicate that IL-10 promoter polymorphisms may enhance the vulnerability of schizophrenia and many diseases,[ 26 39 40 41 42 43 44 45 46 47 48 49 ] while may also exert a protective effect against others. [ 50 51 52 53 ] It has been confirmed by the twin and family studies that ~75% of the variations in IL-10 production is genetically determined.…”

Section: Discussionsupporting

confidence: 55%

Genetic variants of interleukin-10 gene promoter are associated with schizophrenia in Saudi patients: A case-control study

et al. 2014

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Background:Interleukin-10 (IL-10) gene is considered as a potential candidate gene in schizophrenia association studies. The polymorphisms on IL-10 gene have been reported to be linked with susceptibility to the development of schizophrenia within consistent results.Aims:The aim of this case-control study was to examine whether the -1082A/G, -819T/C, and -592A/C polymorphisms in IL-10 gene are implicated in schizophrenia development in the Saudi population.Materials and Methods:Molecular genotyping of IL-10 gene polymorphisms was performed to analyze the genotypes and alleles distribution of three single-nucleotide polymorphisms (SNPs) in patients (n = 181) and healthy individuals as control group (n = 211).Results:The frequencies of GA genotype at -1082, and CC genotype at positions -592 and -819 were significantly higher in schizophrenia patients compared to healthy subjects suggesting that GA, CC, and CC genotypes are susceptible to schizophrenia. The ACC haplotype known to be associated with intermediate production of IL-10 are more prevalent in our schizophrenia patients. On the other hand, genotypes -1082 GG, -819 CT, and -592 CA of IL-10 were more prevalent in healthy controls suggesting protective effects of GA, CT, and CA genotypes against schizophrenia. There was no significant association of IL-10 polymorphisms with sex or positive or negative symptoms of schizophrenia.Conclusion:This study indicates that the IL-10 gene polymorphisms play a significant role in the etiology of schizophrenia in Saudi Arabians patients.

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“…The authors demonstrated that the most significant haplotype was provided by the 6-SNP haplotype window, including rs7182786, rs8028364, rs12907134, rs4128767, rs4072111 and rs8031107, indicating that IL-16 may be a genetic marker for the diagnosis and prognosis of GD in the Taiwanese population ( 22 ). In addition, an association between IL-10 polymorphism and Graves’ disease has been reported in the Turkish population ( 23 ). A recent meta-analysis of 11 case control studies indicated that polymorphisms at the −511 locus of IL-1B are associated with the risk of GD development in Caucasian and Asian individuals in a homozygotic model ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

Expression levels and genetic polymorphisms of interleukin-2 and interleukin-10 as biomarkers of Graves’ disease

Liang

Wen

Dong

et al. 2015

Experimental and Therapeutic Medicine

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The aim of the present study was to determine whether the expression levels of interleukin (IL)-2 and IL-10 may be used as biological markers in Graves’ disease (GD) patients. A total of 256 individuals, including 118 GD patients and 138 healthy individuals, were enrolled into the study. Blood samples were collected from each patient and healthy individual, which were then subjected to enzyme-linked immunosorbent assay (ELISA). Total RNA and total proteins were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. In addition, restriction fragment length polymorphism (RFLP) analysis was performed to detect the presence of genetic polymorphisms. The ELISA results indicated that the IL-2 and IL-10 serum levels in the GD patients were increased by ~5.2 and ~7-fold when compared with the levels in the healthy controls. The results of RT-qPCR indicated that the mRNA expression levels of IL-2 and IL-10 were upregulated in the GD patients when compared with the healthy controls. Furthermore, the western blot analysis results revealed that the protein expression levels of IL-2 and IL-10 were significantly increased in the GD patients. RFLP analysis indicated that the increased number of GG single nucleotide polymorphisms (SNPs) in the GD group were detected in the −330 locus of the IL-2 promoter and the −1082 locus of the IL-10 promoter. In addition, the results indicated that the relatively high rates of homozygous GG SNPs (IL-2 −330T/G and IL-10 −1082A/G polymorphisms) on the alleles may be associated with the incidence of GD. The serum, mRNA and protein expression levels of IL-2 and IL-10 were significantly increased in GD patients when compared with the levels in the healthy controls. In conclusion, the expression levels and genetic polymorphisms of IL-2 and IL-10 may be potential biomarkers for the incidence of Graves’ disease in the population studied.

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Association of Cytokine Gene Polymorphisms (IL6, IL10, TNF-α, TGF-β and IFN-γ) and Graves’ Disease in Turkish Population

Abstract: TNF-α-308GA and IL-6 -174CC gene polymorphisms are involved in susceptibility to GD in Turkish population. The polymorphism hypothesis in pro-inflammatory cytokines might be involved in predisposition to GD.

Cited by 14 publications

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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

Genetic variants of interleukin-10 gene promoter are associated with schizophrenia in Saudi patients: A case-control study

Expression levels and genetic polymorphisms of interleukin-2 and interleukin-10 as biomarkers of Graves’ disease

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