Single nucleotide polymorphisms (SNPs) in key cytokines may modulate food allergy phenotypes
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Single nucleotide polymorphisms (SNPs) can play a direct or indirect role in phenotypic expression in food allergy pathogenesis. Our goal was to quantitate the expression of SNPs in relevant cytokines that were expressed in food allergic patients. SNPs in cytokine genes IL-4 and IL-10 are known to be important in IgE generation and regulation. We examined IL-4 (C-590T), IL-4Rα (1652A/G) and IL-10 (C-627A) SNPs using real-time PCR followed by restriction fragment length polymorphism (RFLP) analysis. Our results show that the AA, AG and GG genotypes for IL-4Rα (1652A/G) polymorphisms were statistically different in radioallergosorbent test (RAST) positive versus negative patients, and although no statistically significant differences were observed between genotypes in the IL-4 (C-590T) and IL-10 (C-627A) SNPs, we observed a significant decrease in IL-4 (C-590T) gene expression and increase in IL-4Rα (1652A/G) and IL-10 (C-627A) gene expression between RAST+ versus RAST− patients, respectively. We also observed significant modulation in the protein expression of IL-4 and IL-10 in the serum samples of the RAST+ patients as compared to the RAST− patients indicating that changes in SNP expression resulted in altered phenotypic response in these patients.
KeywordsSingle nucleotide polymorphisms Cytokines Atopy Food allergy RAST+ IgE
This study was supported by grants from the National Institutes of Health [NIAID-RO1LM009726-01 (SAS); NIDA K01 DA024577 (JR); NIDA-1R21DA030108-01 (SM)] and the Kaleida Health Foundations.
- 1.Branum AM, Lukacs SL (2008) Food allergy among U.S. children: trends in prevalence and hospitalizations. NCHS Data Brief 10:1–8Google Scholar
- 18.Campos Alberto EJ, Shimojo N, Suzuki Y, Mashimo Y, Arima T, Matsuura T, Inoue Y, Yamaide A, Tomiita M, Fujii K, Hata A, Kohno Y (2008) IL-10 gene polymorphism, but not TGF-beta1 gene polymorphisms, is associated with food allergy in a Japanese population. Pediatric Allergy Immunol: Off Pub Eur Soc Pediatric Allergy Immunol 19(8):716–721. doi: 10.1111/j.1399-3038.2007.00709.x Google Scholar
- 21.Mathias CB, Hobson SA, Garcia-Lloret M, Lawson G, Poddighe D, Freyschmidt EJ, Xing W, Gurish MF, Chatila TA, Oettgen HC (2011) IgE-mediated systemic anaphylaxis and impaired tolerance to food antigens in mice with enhanced IL-4 receptor signaling. J Allergy Clin Immunol 127(3):795–805 e791–796. doi: 10.1016/j.jaci.2010.11.009 Google Scholar
- 22.Negoro T, Orihara K, Irahara T, Nishiyama H, Hagiwara K, Nishida R, Takagi H, Satoh K, Yamamoto Y, Shimizu S, Hagiwara T, Ishii M, Tanioka T, Nakano Y, Takeda K, Yoshimura I, Iikura Y, Tobe T (2006) Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children. Pediatric Allergy Immunol: Off Pub Eur Soc Pediatric Allergy Immunol 17(8):583–590. doi: 10.1111/j.1399-3038.2006.00463.x Google Scholar
- 29.Campos E, Shimojo N, Inoue Y, Arima T, Suzuki S, Tomiita M, Matsuura T, Hata A, Suzuki Y, Aoyagi M, Kohno Y (2007) No association of polymorphisms in the 5′ region of the CD14 gene and food allergy in a Japanese population. Allergol Int: Off J Jap Soc Allergol 56(1):23–27. doi: 10.2332/allergolint.O-06-432 Google Scholar
- 31.Kusunoki T, Okafuji I, Yoshioka T, Saito M, Nishikomori R, Heike T, Sugai M, Shimizu A, Nakahata T (2005) SPINK5 polymorphism is associated with disease severity and food allergy in children with atopic dermatitis. J Allergy Clin Immunol 115(3):636–638. doi: 10.1016/j.jaci.2004.12.1114 CrossRefGoogle Scholar
- 35.Mitsuyasu H, Yanagihara Y, Mao XQ, Gao PS, Arinobu Y, Ihara K, Takabayashi A, Hara T, Enomoto T, Sasaki S, Kawai M, Hamasaki N, Shirakawa T, Hopkin JM, Izuhara K (1999) Cutting edge: dominant effect of Ile50Val variant of the human IL-4 receptor alpha-chain in IgE synthesis. J Immunol 162(3):1227–1231Google Scholar