Skip to main content
SpringerLink
Log in

Four genetic variants interact to confer susceptibility to atopic dermatitis in Chinese Han population

  • Original Paper
  • Published:
Molecular Genetics and Genomics Aims and scope Submit manuscript

Abstract

Atopic dermatitis is a chronic inflammatory skin disease and is affected by environmental and genetic factors. Gene–gene/environment interactions are strongly believed to contribute to the genetic risk of common diseases. A number of gene–environment interactions of atopic dermatitis were performed. However, there are few comprehensive investigations on the gene–gene (or genetic variants) interactions for atopic dermatitis. We explored the association model of 6 single nucleotide polymorphisms (SNPs) which were most significant (P < 10E-05) in our previous genome wide association study (GWAS) for atopic dermatitis, and search for the possible genetic variant interactions based on the previous GWAS data using Generalized Multifactor Dimensionality Reduction and Plink 1.07 in the combined sample of 4,636 cases and 13,559 controls. The most significant associated evidence was observed under dominant model for SNPs rs3126085, rs12085366, and rs7701890, recessive model for SNP rs17173197, and additive model for SNPs rs2393903 and rs6010620. Three significant pair–way interactions were observed, including PRKAG2 and FLG SNPs (rs17173197 × rs3126085, P combined = 1.11E-15), PRKAG2 and TMEM232-SLC25A46 SNPs (rs17173197 × rs7701890, P combined = 2.22E-15), PRKAG2 and TNFRSF6B-ZGPAT SNPs (rs17173197 × rs6010620, P combined = 6.66E-16). Besides, a three-way significant interaction among PRKAG2, TMEM232-SLC25A46 and TNFRSF6B-ZGPAT SNPs (rs17173197 × rs7701890 × rs6010620, P combined = 5.99E-15) was observed in this study. These four genetic variant interactions confer susceptibility to atopic dermatitis, and highlight the genetic variant interactions in the etiology of atopic dermatitis in Chinese Han population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Barnes KC (2010) An update on the genetics of atopic dermatitis: scratching the surface in 2009. J Allerg Clin Immunol 125(1):16–29

    Article  CAS  Google Scholar 

  • Brown SJ, McLean WH (2009) Eczema genetics: current state of knowledge and future goals. J Invest Dermatol 129(3):543–552

    Article  CAS  PubMed  Google Scholar 

  • Chan SK, Hill ME, Gullick WJ (2006) The role of the epidermal growth factor receptor in breast cancer. J Mammary Gland Biol Neoplasia 11(1):3–11

    Article  PubMed  Google Scholar 

  • Chechlinska M, Siwicki JK, Gos M, Oczko-Wojciechowska M, Jarzab M, Pfeifer A, Jarzab B, Steffen J (2009) Molecular signature of cell cycle exit induced in human T lymphoblasts by IL-2 withdrawal. BMC Genom 10:261

    Article  Google Scholar 

  • Chen CC, Yang YH, Lin YT, Hsieh SL, Chiang BL (2004) Soluble decoy receptor 3: increased levels in atopic patients. J Allergy Clin Immunol 114(1):195–197

    Article  PubMed  Google Scholar 

  • Cherkassky V, Ma Y (2009) Another look at statistical learning theory and regularization. Neural Net 22(7):958–969

    Article  Google Scholar 

  • Cordell HJ (2009) Detecting gene-gene interactions that underlie human diseases. Nat Rev Genet 10(6):392–404

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • DaVeiga SP (2012) Epidemiology of atopic dermatitis: a review. Allergy Asthma Proc 33(3):227–234

    Article  PubMed  Google Scholar 

  • Ellinghaus D, Baurecht H, Esparza-Gordillo J, Rodriguez E, Matanovic A, Marenholz I, Hubner N, Schaarschmidt H, Novak N, Michel S, Maintz L, Werfel T, Meyer-Hoffert U, Hotze M, Prokisch H, Heim K, Herder C, Hirota T, Tamari M, Kubo M, Takahashi A, Nakamura Y, Tsoi LC, Stuart P, Elder JT, Sun L, Zuo X, Yang S, Zhang X, Hoffmann P, Nothen MM, Folster-Holst R, Winkelmann J, Illig T, Boehm BO, Duerr RH, Buning C, Brand S, Glas J, McAleer MA, Fahy CM, Kabesch M, Brown S, McLean WH, Irvine AD, Schreiber S, Lee YA, Franke A, Weidinger S (2013) High-density genotyping study identifies four new susceptibility loci for atopic dermatitis. Nat Genet 45(7):808–812

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fang C, Siew LQ, Corrigan CJ, Ying S (2010) The role of thymic stromal lymphopoietin in allergic inflammation and chronic obstructive pulmonary disease. Archi Immunol et Therapiae Exp 58(2):81–90

    Article  CAS  Google Scholar 

  • Hirota T, Takahashi A, Kubo M, Tsunoda T, Tomita K, Sakashita M, Yamada T, Fujieda S, Tanaka S, Doi S, Miyatake A, Enomoto T, Nishiyama C, Nakano N, Maeda K, Okumura K, Ogawa H, Ikeda S, Noguchi E, Sakamoto T, Hizawa N, Ebe K, Saeki H, Sasaki T, Ebihara T, Amagai M, Takeuchi S, Furue M, Nakamura Y, Tamari M (2012) Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. Nat Genet 44(11):1222–1226

    Article  CAS  PubMed  Google Scholar 

  • Li M, Liu J-B, Liu Q, Yao M, Cheng R, Xue H, Zhou H, Yao Z (2012) Interactions between FLG mutations and allergens in atopic dermatitis. Arch Dermatol Res 304(10):787–793

    Article  CAS  PubMed  Google Scholar 

  • Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, McCarthy MI, Ramos EM, Cardon LR, Chakravarti A, Cho JH, Guttmacher AE, Kong A, Kruglyak L, Mardis E, Rotimi CN, Slatkin M, Valle D, Whittemore AS, Boehnke M, Clark AG, Eichler EE, Gibson G, Haines JL, Mackay TF, McCarroll SA, Visscher PM (2009) Finding the missing heritability of complex diseases. Nature 461(7265):747–753

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mascia F, Mariani V, Girolomoni G, Pastore S (2003) Blockade of the EGF receptor induces a deranged chemokine expression in keratinocytes leading to enhanced skin inflammation. Am J Pathol 163(1):303–312

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, Goudie DR, Sandilands A, Campbell LE, Smith FJ, O’Regan GM, Watson RM, Cecil JE, Bale SJ, Compton JG, DiGiovanna JJ, Fleckman P, Lewis-Jones S, Arseculeratne G, Sergeant A, Munro CS, El Houate B, McElreavey K, Halkjaer LB, Bisgaard H, Mukhopadhyay S, McLean WH (2006) Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 38(4):441–446

    Article  CAS  PubMed  Google Scholar 

  • Palmieri F (2004) The mitochondrial transporter family (SLC25): physiological and pathological implications. Pflugers Arch 447(5):689–709

    Article  CAS  PubMed  Google Scholar 

  • Pastore S, Mascia F, Mariani V, Girolomoni G (2008) The epidermal growth factor receptor system in skin repair and inflammation. J Invest Dermatol 128(6):1365–1374

    Article  CAS  PubMed  Google Scholar 

  • Ritchie MD, Hahn LW, Roodi N, Bailey LR, Dupont WD, Parl FF, Moore JH (2001) Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet 69(1):138–147

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sun L-D, Xiao F-L, Li Y, Zhou W-M, Tang H-Y, Tang X-F, Zhang H, Schaarschmidt H, Zuo X-B, Foelster-Holst R (2011) Genome-wide association study identifies two new susceptibility loci for atopic dermatitis in the Chinese Han population. Nat Genet 43(7):690–694

    Article  CAS  PubMed  Google Scholar 

  • Tamari M, Hirota T (2014) Genome-wide association studies of atopic dermatitis. J Dermatol 41(3):213–220

    Article  CAS  PubMed  Google Scholar 

  • van den Oord RA, Sheikh A (2009) Filaggrin gene defects and risk of developing allergic sensitisation and allergic disorders: systematic review and meta-analysis. BMJ 9(339):b2433

    Article  Google Scholar 

  • Velez DR, White BC, Motsinger AA, Bush WS, Ritchie MD, Williams SM, Moore JH (2007) A balanced accuracy function for epistasis modeling in imbalanced datasets using multifactor dimensionality reduction. Genet Epidemiol 31(4):306–315

    Article  PubMed  Google Scholar 

  • Willis-Owen SA, Morar N, Willis-Owen CA (2007) Atopic dermatitis: insights from linkage overlap and disease co-morbidity. Expert Rev Mol Med 9(9):1–13

    Article  PubMed  Google Scholar 

  • Yin XY, Zhang R, Cheng H, Pan Q, Shen CB, Fan X, Wang ZX, Sun LD, Yang S, Zhang XJ (2013) Gene-gene interactions between HLA-C, ERAP1, TNFAIP3 and TRAF3IP2 and the risk of psoriasis in the Chinese Han population. Br J Dermatol 169(4):941–943

    Article  CAS  PubMed  Google Scholar 

  • Zuo XB, Sheng YJ, Hu SJ, Gao JP, Li Y, Tang HY, Tang XF, Cheng H, Yin XY, Wen LL, Sun LD, Yang S, Cui Y, Zhang XJ (2014) Variants in TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3 interact to confer risk of systemic lupus erythematosus in Chinese population. Rheumatol Int 34(4):459–464

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by the China Natural Science Foundation Youth Project (No.81301353, 81370044), and China Natural Science Foundation Normal Project (No.81172838). We acknowledge the individuals who participated in this project and their families.

Conflict of interest

None declared.

Author information

Author notes

    Authors and Affiliations

    1. Institute and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China

      Changbing Shen, Longdan Liu, Zengqiong Jiang, Xiaodong Zheng, Li Meng, Xianyong Yin, Yujun Sheng, Jingping Gao, Yang Li, Fusheng Zhou, Fengli Xiao, Liangdan Sun, Yong Cui, Sen Yang, Xianbo Zuo & Xuejun Zhang

    2. The Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China

      Changbing Shen, Longdan Liu, Zengqiong Jiang, Xiaodong Zheng, Li Meng, Xianyong Yin, Yujun Sheng, Jingping Gao, Yang Li, Fusheng Zhou, Fengli Xiao, Liangdan Sun, Yong Cui, Sen Yang, Xianbo Zuo & Xuejun Zhang

    3. Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, China

      Changbing Shen, Longdan Liu, Zengqiong Jiang, Xiaodong Zheng, Li Meng, Xianyong Yin, Yujun Sheng, Jingping Gao, Yang Li, Fusheng Zhou, Fengli Xiao, Liangdan Sun, Yong Cui, Sen Yang, Xianbo Zuo & Xuejun Zhang

    4. Department of Dermatology, The Second Affiliated Hospital, Anhui Medical University, Hefei, China

      Jing Gao & Xuejun Zhang

    5. Department of Dermatology, Shanghai Skin Diseases Hospital, Shanghai, China

      Li Meng

    Authors
    1. Changbing Shen
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Longdan Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Zengqiong Jiang
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Xiaodong Zheng
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Li Meng
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Xianyong Yin
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Jing Gao
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Yujun Sheng
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Jingping Gao
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Yang Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Fusheng Zhou
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Fengli Xiao
      View author publications

      You can also search for this author in PubMed Google Scholar

    13. Liangdan Sun
      View author publications

      You can also search for this author in PubMed Google Scholar

    14. Yong Cui
      View author publications

      You can also search for this author in PubMed Google Scholar

    15. Sen Yang
      View author publications

      You can also search for this author in PubMed Google Scholar

    16. Xianbo Zuo
      View author publications

      You can also search for this author in PubMed Google Scholar

    17. Xuejun Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Xianbo Zuo or Xuejun Zhang.

    Additional information

    Communicated by S. Hohmann.

    C. Shen, L. Liu, and Z. Jiang contributed equally to this work and shared first authorship.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Shen, C., Liu, L., Jiang, Z. et al. Four genetic variants interact to confer susceptibility to atopic dermatitis in Chinese Han population. Mol Genet Genomics 290, 1493–1498 (2015). https://doi.org/10.1007/s00438-015-1014-x

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00438-015-1014-x

    Keywords

    Search

    Navigation