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Epistatic interactions between HLA-DRB1 and interleukin 4, but not interferon-gamma, increase susceptibility to giant cell arteritis.

Amoli MM, Gonzalez-Gay M, Zeggini E, Salway F, Garcia-Porrua C, Ollier WER

J Rheumatol. 2004;31( 12):2413-7.

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OBJECTIVE: To assess the roles of the interleukin 4 (IL-4) and interferon-g (IFN-g) gene polymorphisms in a series of patients with biopsy-proven giant cell arteritis (GCA). METHODS: Eighty-two patients with biopsy-proven GCA and 102 ethnically matched controls from the Lugo region (Northwest Spain) were studied. The following single nucleotide polymorphisms (SNP) were assessed: IL-4 (SNP1: rs2070874, SNP2: rs2227284, SNP3: rs2227282, SNP4: rs2243266, and SNP5: rs2243267) and IFN-g (SNP1: rs1861494, SNP2: rs1861493, and SNP3: rs2069718). RESULTS: Significant differences in allele and genotype frequencies were observed for the IL-4 SNP between HLA-DRB1*04 negative patients and controls. Epistatic interaction between SNP2 (rs2227284) with HLA-DRB1 showed a significant interaction (p = 0.001) and carriage of the SNP2*T allele in the absence of HLA-DRB1*04 resulted in a 4-fold risk of developing GCA (OR 4.2, 95% CI 1.1-15.6). Also, a significant increase in the frequency of the T-T-C-A-C IL-4 haplotype was observed in HLA-DRB1*04 negative GCA patients compared to the controls (p = 0.02; OR 2.0, 95% CI 1.0-3.9). Similar distributions of allele and genotype frequencies were observed for the IFN-g polymorphisms in both GCA patients and controls. CONCLUSION: Our results suggest an association with IL-4 gene polymorphism that is dependent on HLA-DRB1 genotype in GCA susceptible individuals. These data indicate an interaction between HLA-DRB1 and IL-4 that contributes to pronounced disease susceptibility.

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31( 12)
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29th August, 2009, 15:08:21
Last modified:
20th July, 2015, 12:57:10

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