Polymorphisms of interleukin-21 and interleukin-21-receptor genes confer risk for autoimmune thyroid diseases

Abstract

BackgroundThe abnormality of interleukin-21 (IL-21)-IL-21-receptor (IL-21R) system has been found in many autoimmune diseases including autoimmune thyroid diseases (AITDs). In this study, we investigated whether polymorphisms of the IL-21 and IL-21R are associated with Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), two major forms of AITDs, among a Chinese population.MethodsRs907715, rs4833837, rs2221903 and rs2055979 of the IL-21 gene and rs3093301 and rs2285452 of the IL-21R gene were explored in a case–control study including 405 GD, 228 HT patients and 242 controls. These genes were genotyped by the PCR and restriction fragment length polymorphism (RFLP) analysis and the MASS spectrometry method.ResultsFor IL-21 gene, we identified and confirmed a higher prevalence of A alleles of rs2221903 (P = 0.018, OR = 1.50 95% CI = 1.07-2.09) in GD patients. We also found a significant association between rs2221903 and HT (allele: P = 0.009, OR = 1.69 95% CI = 1.13-2.51; genotype: recessive P = 0.021, OR = 11.72 95% CI = 1.46-94.13). For the IL-21R gene, compared with controls, the genotype frequencies of rs3093301 and rs2285452 were significantly different in HT patients using dominant genetic model (P = 0.023, OR = 1.61 95% CI = 1.07-2.42; P = 0.031, OR = 1.71 95% CI = 1.05-2.80, respectively). Furthermore, the haplotype AA containing the major alleles of rs4833837 and rs2221903 was associated with increased susceptibility to GD with an OR of 1.50(95% CI =1.08-2.09, P = 0.016), and to HT with an OR of 1.69(95% CI =1.14-2.52, P = 0.009).ConclusionOur results indicated that the SNPs of the IL-21 gene is associated with the development of GD. In addition, we found that individuals with the SNPs of the common IL-21 and IL-21R may have higher risk of HT.

Polymorphism in interleukin 21 gene is associated with decreased susceptibility to diffuse large B cell lymphoma

“…In addition, You et al have reported that The IL-21 −2498A allele predicts longer 5-year survival in breast cancer patients [19]. Our data showed that −2498GA and AA genotypes were associated with decreased susceptibility to DLBCL in the Chinese population ( [20]. However, we did not identify any correlation between IL-21 +78A/G SNP and DLBCL in our study population.…”

WITHDRAWN: Interleukin-21 receptor gene polymorphism is associated with hepatitis B virus-related hepatocellular carcinoma in Chinese patients

“…The patients with the AA genotype of IL-21R rs2285452 show higher risk of HBV-related HCC than those with the AG/GG genotype. In a previous study, the IL-21R rs2285452 polymorphism showed differential genotype distribution in Hashimoto's thyroiditis (HT) and control subjects [40]. Moreover, the IL-21 rs2221903 and IL-21R rs3093301 polymorphisms were associated with chronic HBV infection, an interactive role of IL21R rs3093301 CC with IL21 rs2221903 in inducing the elevation of IL-21 and IgE production in the HBV patients, thereby suggesting that the SNPs in the IL-21 and IL-21R genes influence the susceptibility and persistence of HBV by affecting serum IL-21 and IgE levels [38].…”

TSHR intronic polymorphisms (rs179247 and rs12885526) and their role in the susceptibility of the Brazilian population to Graves’ disease and Graves’ ophthalmopathy

“…About 25-50 % of GD patients have clinical signs of Graves' ophthalmopathy (GO), most having mild disease [2,3]. Genome-wide screens conducted in GD have identified a number of putative susceptibility genes in GD [4] and several gene loci have been reported to be associated with a risk of developing GD, including HLA [4,5], CTLA4 [6], PTPN22 [7], CD40 [8], IL2RA [9], IL21 [10], and TG [11]. About 20 identified genetic polymorphisms, including both thyroid-specific genes and those regulating the autoimmune response were already investigated.…”