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Association of ORAI1 gene polymorphisms with chronic spontaneous urticaria and the efficacy of the nonsedating H1 antihistamine desloratadine Jie Li, MD, PhD, Aiyuan Guo, MD, PhD, Wangqing Chen, PhD, Lianghua Bin, PhD, Yijing He, MD, PhD, Wu Zhu, MD, PhD, Cong Peng, PhD, Siyu Yan, MD, Mingliang Chen, MD, PhD, Jianglin Zhang, MD, PhD, Juan Su, MD, PhD, Mei Yi, MD, PhD, Zhaoqian Liu, MD, PhD, Wei Zhang, MD, PhD, Weiqi Zeng, PhD, Donald Y.M. Leung, MD, PhD, Xiang Chen, MD, PhD Journal of Allergy and Clinical Immunology Volume 139, Issue 4, Pages e9 (April 2017) DOI: /j.jaci Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig 1 CSU susceptibility-associated ORAI1 SNPs have increased promoter activation and mast cell degranulation. A, ORAI1 promotor with rs T allele has increased promoter activation than ORAI1 with rs G allele determined by reporter gene assays. B, ORAI1 gene expression in PBMCs was evaluated by real-time PCR. Subjects who carried the rs TT genotype (n = 7) have increased ORAI mRNA levels as compared with subjects who carried the rs GG genotype (n = 5). C, The resting [Ca2+] influx (black bar) and the thapsigargin (TG) evoking [Ca2+] influx (gray bar) are significantly increased in RBL-2H3 cells that overexpressed the rs A allele than RBL-2H3 cells that overexpressed the rs G allele. D, The β-HEX release by phorbol 12-myristate 13-acetate and ionomycin stimulation was evaluated in RBL-2H3 cells with different rs alleles. Cells were first silenced for ORAI1 gene (siRNA-ORAI1) and then reconstituted with different rs alleles. Cells with rs A (ORAI1-A, 0.81 ± 0.05) have significantly greater β-HEX release than do cells with rs G (ORAI1-G, 0.61 ± 0.04). Data were presented as mean ± SD of at least 4 independent experiments performed in triplicate. β-HEX, β-Hexosaminidase. Journal of Allergy and Clinical Immunology , e9DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig E1 Site of each SNP in ORAI1 gene. Both rs and rs are located in the promoter region of ORAI1. rs and rs are located in the exon; the former results in a synonymous mutation, whereas the latter is a nonsynonymous mutation leading to the replacement of Serine by Glycine at amino acid 218. TSS, Transcription start site. Journal of Allergy and Clinical Immunology , e9DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig E2 LD (linkage disequilibrium) heatmap of the linkage disequilibrium (D′, r2) among the 4 SNPs. Linkage disequilibrium was assessed through the Web site r2 more than 0.8 means SNPs linkage disequilibrium. All r2 values were less than 0.8 between the different SNPs. Journal of Allergy and Clinical Immunology , e9DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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