Inflammation Research

, Volume 65, Issue 7, pp 573–578 | Cite as

Interaction between STAT3 gene polymorphisms and smoking on Crohn’s disease susceptibility: a case–control study in a Chinese Han population

  • Jun-hong Li
  • Ning Wu
  • Hong-mei Yang
  • Hong-bing Tang
  • Dong-ping Bao
  • Jun-min Ji
Original Research Paper
  • 212 Downloads

Abstract

Aims

The aim of this study was to investigate the impact of the signal transducer and activator of transcription 3 (STAT3) gene and additional STAT3 gene–smoking interaction on Crohn’s disease (CD) risk based on a Chinese population.

Methods

A total of 1012 participants (491 men, 521 women), were selected, including 502 CD patients and 510 normal controls. The mean age of all participants was 42.3 ± 11.2 years. Logistic regression model was used to examine the association between single nucleotide polymorphism (SNP) of STAT3 and CD risk; the odds ratio (OR) and 95 % confident interval (95 % CI) were calculated. Generalized multifactor dimensionality reduction was employed to analyze the interaction among several SNPs.

Results

Logistic analysis showed the significant association between genotypes of variants in two SNP and decreased CD risk, after covariates adjustment. The carriers of homozygous mutant of two SNP polymorphism revealed decreased CD risk than those with wild-type homozygotes; OR (95 % CI) was 0.75 (0.59–0.93) and 0.68 (0.57–0.91), respectively. There was a significant two-locus model (p = 0.0107) involving rs744166 and smoking, indicating a potential gene–environment interaction between rs744166 and smoking. Overall, the cross-validation consistency was 10/10, and the testing accuracy was 62.17 %, and never smokers with TC or CC genotype have the lowest CD risk, compared to smokers with TT genotype; OR (95 % CI) was 0.52 (0.31–0.82), after covariate adjustment.

Conclusions

Our results support an important association of rs744166 and rs4796793 with decreased CD risk, and additional interaction between rs744166 and smoking.

Keywords

STAT3 Smoking Interaction Crohn’s disease SNP 

Notes

Acknowledgments

The writing of this paper was supported by Changzhou Center for Disease Control and Prevention and the First Hospital of Hengyang. We thank all the partners and staff who helped us in the process of this study.

Compliance with ethical standards

Conflict of interest

There is no conflict of interest.

References

  1. 1.
    Ng SC, Bernstein CN, Vatn MH, Lakatos PL, Loftus EV Jr, Tysk C, O’Morain C, Moum B, Colombel JF. Epidemiology and Natural history task force of the International Organization of inflammatory bowel disease (IOIBD). Geographical variability and environmental risk factors in inflammatory bowel disease. Gut. 2013;62:630–49.CrossRefPubMedGoogle Scholar
  2. 2.
    Zheng CQ, Hu GZ, Zeng ZS, Lin LJ, Gu GG. Progress in searching for susceptibility gene for inflammatory bowel disease by positional cloning. World J Gastroenterol. 2003;9(8):1646–56.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Molodecky NA, Kaplan GG. Environmental risk factors for inflammatory bowel disease. Gastroenterol Hepatol (NY). 2010;6(5):339–46.Google Scholar
  4. 4.
    Cho JH. The genetics and immunopathogenesis of inflammatory bowel disease. Nat Rev Immunol. 2008;8(6):458–66.CrossRefPubMedGoogle Scholar
  5. 5.
    Stumhofer JS, Silver JS, Laurence A, Porrett PM, Harris TH, Turka LA, Ernst M, Saris CJ, O’Shea JJ, Hunter CA. Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nat Immunol. 2007;8(12):1363–71.CrossRefPubMedGoogle Scholar
  6. 6.
    Laouar Y, Welte T, Fu XY, Flavell RA. STAT3 is required for Flt3L-dependent dendritic cell differentiation. Immunity. 2003;19(6):903–12.CrossRefPubMedGoogle Scholar
  7. 7.
    Akira S. Roles of STAT3 defined by tissue-specific gene targeting. Oncogene. 2000;19(21):2607–11.CrossRefPubMedGoogle Scholar
  8. 8.
    Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, Brant SR, Silverberg MS, Taylor KD, Barmada MM, Bitton A, Dassopoulos T, Datta LW, Green T, Griffiths AM, Kistner EO, Murtha MT, Regueiro MD, Rotter JI, Schumm LP, Steinhart AH, Targan SR, Xavier RJ, Genetics Consortium NIDDKIBD, Libioulle C, Sandor C, Lathrop M, Belaiche J, Dewit O, Gut I, Heath S, Laukens D, Mni M, Rutgeerts P, Van Gossum A, Zelenika D, Franchimont D, Hugot JP, de Vos M, Vermeire S, Louis E, Belgian-French IBD Consortium, Cardon LR, Anderson CA, Drummond H, Nimmo E, Ahmad T, Prescott NJ, Onnie CM, Fisher SA, Marchini J, Ghori J, Bumpstead S, Gwilliam R, Tremelling M, Deloukas P, Mansfield J, Jewell D, Satsangi J, Mathew CG, Parkes M, Georges M, Daly MJ. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet. 2008;40(8):955–62.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Sato K, Shiota M, Fukuda S, Iwamoto E, Machida H, Inamine T, Kondo S, Yanagihara K, Isomoto H, Mizuta Y, Kohno S, Tsukamoto K. Strong evidence of a combination polymorphism of the tyrosine kinase 2 gene and the signal transducer and activator of transcription 3 gene as a DNA-based biomarker for susceptibility to Crohn’s disease in the Japanese population. J Clin Immunol. 2009;29(6):815–25.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Ferguson LR, Han DY, Fraser AG, Huebner C, Lam WJ, Morgan AR, Duan H, Karunasinghe N. Genetic factors in chronic inflammation: single nucleotide polymorphisms in the STAT-JAK pathway, susceptibility to DNA damage and Crohn’s disease in a New Zealand population. Mutat Res. 2010;690(1–2):108–15.CrossRefPubMedGoogle Scholar
  11. 11.
    Cénit MC, Alcina A, Márquez A, Mendoza JL, Díaz-Rubio M, de las Heras V, Izquierdo G, Arroyo R, Fernández O, de la Concha EG, Matesanz F, Urcelay E. STAT3 locus in inflammatory bowel disease and multiple sclerosis susceptibility. Genes Immun. 2010;11(3):264–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Peter I, Mitchell AA, Ozelius L, Erazo M, Hu J, Doheny D, Abreu MT, Present DH, Ullman T, Benkov K, Korelitz BI, Mayer L, Desnick RJ, New York Crohn’s Disease Working Group. Evaluation of 22 genetic variants with Crohn’s disease risk in the Ashkenazi Jewish population: a case–control study. BMC Med Genet. 2011;12:63.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Franke A, Balschun T, Karlsen TH, Hedderich J, May S, Lu T, Schuldt D, Nikolaus S, Rosenstiel P, Krawczak M, Schreiber S. Replication of signals from recent studies of Crohn’s disease identifies previously unknown disease loci for ulcerative colitis. Nat Genet. 2008;40:713–5.CrossRefPubMedGoogle Scholar
  14. 14.
    Polgar N, Csongei V, Szabo M, Zambo V, Melegh BI, Sumegi K, Nagy G, Tulassay Z, Melegh B. Investigation of JAK2, STAT3 and CCR6 polymorphisms and their gene–gene interactions in inflammatory bowel disease. Int J Immunogenet. 2012;39(3):247–52.CrossRefPubMedGoogle Scholar
  15. 15.
    Wang Z, Xu B, Zhang H, Fan R, Zhou J, Zhong J. Association between STAT3 gene Polymorphisms and Crohn’s disease susceptibility: a case–control study in a Chinese Han population. Diagn Pathol. 2014;9:104.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Ryan BM, Wolff RK, Valeri N, Khan M, Robinson D, Paone A, Bowman ED, Lundgreen A, Caan B, Potter J, Brown D, Croce C, Slattery ML, Harris CC. An analysis of genetic factors related to risk of inflammatory bowel disease and colon cancer. Cancer Epidemiol. 2014;38(5):583–90.CrossRefPubMedGoogle Scholar
  17. 17.
    Lohman T, Roche AF, Martorell R. Standardization of anthropometric measurements. Champaign: Human Kinetics; 1988.Google Scholar
  18. 18.
    China Nutrition Society. Chinese residents dietary guide [M]. Beijing: Tibet people’s press; 2008. p. 15–55.Google Scholar
  19. 19.
    Lou XY, Chen GB, Yan L, Ma JZ, Zhu J, Elston RC, Li MD. A generalized combinatorial approach for detecting gene-by gene and gene-by-environment interactions with application to nicotine dependence. Am J Hum Genet. 2007;80(6):1125–37.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Cosin-Aguilar J, Andres-Conejos F, Hernandiz-Martinez A, Solaz-Minguez J, Marrugat J, Bayes-De-Luna A. Effect of smoking on sudden and premature death. J Cardiovasc Risk. 1995;2(4):345–51.CrossRefPubMedGoogle Scholar
  21. 21.
    Mahid SS, Minor KS, Soto RE, Hornung CA, Galandiuk S. Smoking and inflammatory bowel disease: a meta-analysis. Mayo Clin Proc. 2006;81:1462–71.CrossRefPubMedGoogle Scholar
  22. 22.
    Higuchi LM, Khalili H, Chan AT, Richter JM, Bousvaros A, Fuchs CS. A prospective study of cigarette smoking and the risk of inflammatory bowel disease in women. Am J Gastroenterol. 2012;107:1399–406.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Matalka II, Al-Omari FA, Salama RM, Mohtaseb AH. A novel approach for quantitative assessment of mucosal damage in inflammatory bowel disease. Diagn Pathol. 2013;8:156.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Larsen EP, Bayat A, Vyberg M. Small duct autoimmune sclerosing cholangitis and Crohn colitis in a 10-year-old child. A case report and review of the literature. Diagn Pathol. 2012;7:100.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  • Jun-hong Li
    • 1
  • Ning Wu
    • 2
  • Hong-mei Yang
    • 3
  • Hong-bing Tang
    • 1
  • Dong-ping Bao
    • 1
  • Jun-min Ji
    • 1
  1. 1.Inspection CenterChangzhou Center for Disease Control and PreventionChangzhouPeople’s Republic of China
  2. 2.Department of Clinical LaboratoryThe First Hospital of HengyangHengyangPeople’s Republic of China
  3. 3.Department of Blood Quality ManagementChangzhou Blood CenterChangzhouPeople’s Republic of China

Personalised recommendations