The Role of IFIH1 Gene Rs1990760 and Rs2111485 Single-nucleotide Polymorphisms in Generalized Vitiligo Predisposition

Overview

Journal Turk J Med Sci

Specialty General Medicine

Date 2019 Feb 15

PMID 30761886

Citations 2

Authors

Duru Onan

Ahu Yorulmaz

Fatih Suheyl Ezgu

Kadir Mutlu Hayran

Seray Kulcu

Refika Ferda Artuz

Basak Yalcin

Affiliations

Soon will be listed here.

Abstract

Background/aim: Interferon-induced helicase (IFIH1) is a gene locus that has been recently defined as a candidate for susceptibility to generalized vitiligo (GV). The objectives of this study were to assess the association of IFIH1 gene, rs2111485, and rs1990760 single-nucleotide polymorphisms (SNP) with susceptibility to GV and the autoimmune diseases accompanying GV.

Materials And Methods: We prospectively studied GV patients and frequency-matched healthy controls by age and sex. The genotypes of the participants were determined for rs1990760 and rs2111485 SNPs of IFIH1. Dominant, recessive, and additive models were evaluated for each SNP adjusted for age and sex.

Results: The patients and their controls were observed to be in the Hardy–Weinberg equilibrium for SNP1 (2q24.2, rs1990760, IFIH1, T/C) and SNP2 (2q24.2, rs2111485, IFIH1, G/A), respectively (all P > 0.7). For SNP1, every T allel addition was significantly associated with 1.53 times protectiveness in terms of vitiligo risk (P = 0.033). As for SNP2, every G allel addition was associated with 1.42 times protectiveness, close to statistical significance (P = 0.100).

Conclusions: We detected that for SNP1, each T allel and for SNP2, each G allel are protective in terms of vitiligo development. Hereby, we confirmed that IFIH1 gene locus has a role in GV susceptibility.

Citing Articles

Association Among , and Gene Polymorphisms and Non-Segmental Vitiligo in a Chinese Han Population.

Wang D, Min S, Lin X, Jiang G Clin Cosmet Investig Dermatol. 2022; 15:1597-1609.

PMID: 35983127 PMC: 9380431. DOI: 10.2147/CCID.S369418.

Association of rs4711998 of IL-17A, rs2275913 of IL-17A and rs763780 IL-17F gene polymorphisms with non-segmental vitiligo in a Mexican population.

Zapata-Salazar N, Kubelis-Lopez D, Salinas-Santander M, Sanchez-Dominguez C, Xolalpa-Rosales A, Gomez-Galindo M Arch Dermatol Res. 2022; 315(3):447-454.

PMID: 35960353 DOI: 10.1007/s00403-022-02382-8.

References

Gill L, Zarbo A, Isedeh P, Jacobsen G, Lim H, Hamzavi I . Comorbid autoimmune diseases in patients with vitiligo: A cross-sectional study. J Am Acad Dermatol. 2015; 74(2):295-302. DOI: 10.1016/j.jaad.2015.08.063. View

Yin X, Low H, Wang L, Li Y, Ellinghaus E, Han J . Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility. Nat Commun. 2015; 6:6916. PMC: 4423213. DOI: 10.1038/ncomms7916. View

Shigemoto T, Kageyama M, Hirai R, Zheng J, Yoneyama M, Fujita T . Identification of loss of function mutations in human genes encoding RIG-I and MDA5: implications for resistance to type I diabetes. J Biol Chem. 2009; 284(20):13348-13354. PMC: 2679434. DOI: 10.1074/jbc.M809449200. View

Spritz R . Recent progress in the genetics of generalized vitiligo. J Genet Genomics. 2011; 38(7):271-8. PMC: 3513342. DOI: 10.1016/j.jgg.2011.05.005. View

Spritz R . The genetics of generalized vitiligo and associated autoimmune diseases. Pigment Cell Res. 2007; 20(4):271-8. DOI: 10.1111/j.1600-0749.2007.00384.x. View

Jin Y, Andersen G, Santorico S, Spritz R . Multiple Functional Variants of IFIH1, a Gene Involved in Triggering Innate Immune Responses, Protect against Vitiligo. J Invest Dermatol. 2016; 137(2):522-524. DOI: 10.1016/j.jid.2016.09.021. View

Czajkowski R, Mecinska-Jundzill K . Current aspects of vitiligo genetics. Postepy Dermatol Alergol. 2014; 31(4):247-55. PMC: 4171675. DOI: 10.5114/pdia.2014.43497. View

Martinez A, Santiago J, Cenit M, de Las Heras V, De La Calle H, Fernandez-Arquero M . IFIH1-GCA-KCNH7 locus: influence on multiple sclerosis risk. Eur J Hum Genet. 2008; 16(7):861-4. DOI: 10.1038/ejhg.2008.16. View

Smyth D, Cooper J, Bailey R, Field S, Burren O, Smink L . A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region. Nat Genet. 2006; 38(6):617-9. DOI: 10.1038/ng1800. View

10.

Spritz R, Andersen G . Genetics of Vitiligo. Dermatol Clin. 2017; 35(2):245-255. PMC: 5362127. DOI: 10.1016/j.det.2016.11.013. View

11.

Looney B, Xia C, Concannon P, Ostrov D, Clare-Salzler M . Effects of type 1 diabetes-associated IFIH1 polymorphisms on MDA5 function and expression. Curr Diab Rep. 2015; 15(11):96. DOI: 10.1007/s11892-015-0656-8. View

12.

Jin Y, Andersen G, Yorgov D, Ferrara T, Ben S, Brownson K . Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants. Nat Genet. 2016; 48(11):1418-1424. PMC: 5120758. DOI: 10.1038/ng.3680. View

13.

Richmond J, Frisoli M, Harris J . Innate immune mechanisms in vitiligo: danger from within. Curr Opin Immunol. 2013; 25(6):676-82. PMC: 3935321. DOI: 10.1016/j.coi.2013.10.010. View

14.

Nejentsev S, Walker N, Riches D, Egholm M, Todd J . Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes. Science. 2009; 324(5925):387-9. PMC: 2707798. DOI: 10.1126/science.1167728. View

15.

Nakashima R, Imura Y, Kobayashi S, Yukawa N, Yoshifuji H, Nojima T . The RIG-I-like receptor IFIH1/MDA5 is a dermatomyositis-specific autoantigen identified by the anti-CADM-140 antibody. Rheumatology (Oxford). 2009; 49(3):433-40. DOI: 10.1093/rheumatology/kep375. View

16.

Cen H, Wang W, Leng R, Wang T, Pan H, Fan Y . Association of IFIH1 rs1990760 polymorphism with susceptibility to autoimmune diseases: a meta-analysis. Autoimmunity. 2013; 46(7):455-62. DOI: 10.3109/08916934.2013.796937. View

17.

Li Y, Liao W, Cargill M, Chang M, Matsunami N, Feng B . Carriers of rare missense variants in IFIH1 are protected from psoriasis. J Invest Dermatol. 2010; 130(12):2768-72. PMC: 3680368. DOI: 10.1038/jid.2010.214. View

18.

Jin Y, Birlea S, Fain P, Ferrara T, Ben S, Riccardi S . Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo. Nat Genet. 2012; 44(6):676-80. PMC: 3366044. DOI: 10.1038/ng.2272. View

19.

Gateva V, Sandling J, Hom G, Taylor K, Chung S, Sun X . A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet. 2009; 41(11):1228-33. PMC: 2925843. DOI: 10.1038/ng.468. View

20.

Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K . Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature. 2006; 441(7089):101-5. DOI: 10.1038/nature04734. View