Skip to main content
SpringerLink
Log in

MEFV E148Q polymorphism is associated with Henoch–Schönlein purpura in Chinese children

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Henoch–Schönlein purpura (HSP) is a multifactorial inflammatory disease whose pathogenesis remains unknown. Pyrin encoded by the MEFV gene (NM_000243; OMIM 608107) is an important active member of the inflammasome and has been shown to affect the expression of many of the genes involved in immune and inflammatory responses. The aim of our study was to elucidate the possible roles of MEFV genetic variants on the susceptibility to HSP and its clinical outcomes in 78 patients with HSP and 189 controls in China. A significant association was found between the E148Q polymorphism (G->C) and HSP susceptibility (odds ratio 2.76, 95% confidence interval 1.76-4.34, P=0.0001). The C allele of E148Q was associated with joint involvement (P = 0.014) but not with HSP nephritis (P = 0.1). The clinical score was higher in subjects with the CC genotype than in those with the CG or GG genotype (4.13 ± 3.53 vs. 1.94 ± 1.70, respectively; P = 0.011). P369S was not associated with HSP or other phenotypes. M694V and M680I were absent in our patients. Our results suggest that MEFV E148Q could be a contributory genetic factor to HSP and HSP-related joint syndromes.

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

  1. Gardner-Medwin JM, Dolezalova P, Cummins C, Southwood TR (2002) Incidence of Henoch–Schönlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins. Lancet 360:1197–1202

    Article  PubMed  Google Scholar 

  2. Yang YH, Hung CF, Hsu CR, Wang LC, Chuang YH, Lin YT, Chiang BL (2005) A nationwide survey on epidemiological characteristics of childhood Henoch—Schönlein purpura in Taiwan. Rheumatology (Oxford) 44:618–622

    Article  Google Scholar 

  3. Brogan PA (2007) What’s new in the aetiopathogenesis of vasculitis? Pediatr Nephrol 22:1083–1094

    Article  PubMed  Google Scholar 

  4. Chae JJ, Wood G, Masters SL, Richard K, Park G, Smith BJ, Kastner DL (2006) The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1beta production. Proc Natl Acad Sci USA 103:9982–9987

    Article  CAS  PubMed  Google Scholar 

  5. Chae JJ, Wood G, Richard K, Jaffe H, Colburn NT, Masters SL, Gumucio DL, Shoham NG, Kastner DL (2008) The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-kappaB through its N-terminal fragment. Blood 112:1794–1803

    Article  CAS  PubMed  Google Scholar 

  6. Milhavet F, Cuisset L, Hoffman HM, Slim R, El-Shanti H, Aksentijevich I, Lesage S, Waterham H, Wise C, Sarrauste de Menthiere C, Touitou I (2008) The infevers autoinflammatory mutation online registry: update with new genes and functions. Hum Mutat 29:803–808

    Article  PubMed  Google Scholar 

  7. Villani AC, Lemire M, Louis E, Silverberg MS, Collette C, Fortin G, Nimmo ER, Renaud Y, Brunet S, Libioulle C, Belaiche J, Bitton A, Gaudet D, Cohen A, Langelier D, Rioux JD, Arnott ID, Wild GE, Rutgeerts P, Satsangi J, Vermeire S, Hudson TJ, Franchimont D (2009) Genetic variation in the familial Mediterranean fever gene (MEFV) and risk for Crohn’s disease and ulcerative colitis. PLoS ONE 4:e7154

    Article  PubMed  Google Scholar 

  8. Ayaz NA, Ozen S, Bilginer Y, Ergüven M, Taşkiran E, Yilmaz E, Beşbaş N, Topaloğlu R, Bakkaloğlu A (2009) MEFV mutations in systemic onset juvenile idiopathic arthritis. Rheumatology (Oxford) 48:23–25

    Article  CAS  Google Scholar 

  9. Ozen S, Bakkaloglu A, Yilmaz E, Duzova A, Balci B, Topaloglu R, Besbas N (2003) Mutations in the gene for familial Mediterranean fever: do they predispose to inflammation? J Rheumatol 30:2014–2018

    CAS  PubMed  Google Scholar 

  10. Migita K, Nakamura T, Maeda Y, Miyashita T, Koga T, Tanaka M, Nakamura M, Komori A, Ishibashi H, Origuchi T, Ida H, Kawasaki E, Yasunami M, Eguchi K (2008) MEFV mutations in Japanese rheumatoid arthritis patients. Clin Exp Rheumatol 26:1091–1094

    CAS  PubMed  Google Scholar 

  11. Durmus D, Alayli G, Cengiz K, Yigit S, Canturk F, Bagci H (2009) Clinical significance of MEFV mutations in ankylosing spondylitis. Joint Bone Spine 76:260–264

    Article  PubMed  Google Scholar 

  12. Yurtcu E, Gokcan H, Yilmaz U, Sahin FI (2009) Detection of MEFV gene mutations in patients with inflammatory bowel disease. Genet Test Mol Biomarkers 13:87–90

    Article  CAS  PubMed  Google Scholar 

  13. Gershoni-Baruch R, Broza Y, Brik R (2003) Prevalence and significance of mutations in the familial Mediterranean fever gene in Henoch-Schönlein purpura. J Pediatr 143:658–661

    Article  CAS  PubMed  Google Scholar 

  14. Ozçakar ZB, Yalçinkaya F, Cakar N, Acar B, Kasapçopur O, Ugüten D, Soy D, Kara N, Uncu N, Arisoy N, Ekim M (2008) MEFV mutations modify the clinical presentation of Henoch–Schönlein purpura. J Rheumatol 35:2427–2429

    Article  PubMed  Google Scholar 

  15. Tomiyama N, Higashiuesato Y, Oda T, Baba E, Harada M, Azuma M, Yamashita T, Uehara K, Miyazato A, Hatta K, Ohya Y, Iseki K, Jinno Y, Takishita S (2008) MEFV mutation analysis of familial Mediterranean fever in Japan. Clin Exp Rheumatol 26:13–17

    CAS  PubMed  Google Scholar 

  16. Tsuchiya-Suzuki A, Yazaki M, Nakamura A, Yamazaki K, Agematsu K, Matsuda M, Ikeda S (2009) Clinical and genetic features of familial Mediterranean fever in Japan. J Rheumatol 36:1671–1676

    Article  CAS  PubMed  Google Scholar 

  17. Ozdogan H, Arisoy N, Kasapçapur O, Sever L, Calişkan S, Tuzuner N, Mat C, Yazici H (1997) Vasculitis in familial Mediterranean fever. J Rheumatol 24:323–327

    CAS  PubMed  Google Scholar 

  18. Yilmaz E, Ozen S, Balci B, Duzova A, Topaloglu R, Besbas N, Saatci U, Bakkaloglu A, Ozguc M (2001) Mutation frequency of Familial Mediterranean Fever and evidence for a high carrier rate in the Turkish population. Eur J Hum Genet 9:553–555

    Article  CAS  PubMed  Google Scholar 

  19. Mills JA, Michel BA, Bloch DA, Calabrese LH, Hunder GG, Arend WP, Edworthy SM, Fauci AS, Leavitt RY, Lie JT, Lightfoot RW Jr, Masi AT, McShane DJ, Stevens MB, Wallace SL, Zvaifler NJ (1990) The American College of Rheumatology 1990 criteria for the classification of Henoch–Schönlein purpura. Arthritis Rheum 33:1114–1121

    Article  CAS  PubMed  Google Scholar 

  20. Yang YH, Lai HJ, Kao CK, Lin YT, Chiang BL (2004) The association between transforming growth factor-beta gene promoter C-509T polymorphism and Chinese children with Henoch–Schönlein purpura. Pediatr Nephrol 19:972–975

    Article  PubMed  Google Scholar 

  21. Soylemezoglu O, Peru H, Gonen S, Cetinyurek A, Buyan N (2008) HLA-DRB1 alleles and Henoch–Schönlein purpura: susceptibility and severity of disease. J Rheumatol 35:1165–1168

    PubMed  Google Scholar 

  22. Aksentijevich I, Torosyan Y, Samuels J, Centola M, Pras E, Chae JJ, Oddoux C, Wood G, Azzaro MP, Palumbo G, Giustolisi R, Pras M, Ostrer H, Kastner DL (1999) Mutation and haplotype studies of familial Mediterranean fever reveal new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population. Am J Hum Genet 64:949–962

    Article  CAS  PubMed  Google Scholar 

  23. Balci B, Tinaztepe K, Yilmaz E, Guçer S, Ozen S, Topaloğlu R, Beşbaş N, Ozguç M, Bakkaloğlu A (2002) MEFV gene mutations in familial Mediterranean fever phenotype II patients with renal amyloidosis in childhood: a retrospective clinicopathological and molecular study. Nephrol Dial Transplant 17:1921–1923

    Article  CAS  PubMed  Google Scholar 

  24. Turanli ET, Beger T, Erdincler D, Curgunlu A, Karaman S, Karaca E, Dasdemir S, Bolayirli M, Yazici H (2009) Common MEFV mutations and polymorphisms in an elderly population: an association with E148Q polymorphism and rheumatoid factor levels. Clin Exp Rheumatol 27:340–343

    CAS  PubMed  Google Scholar 

  25. Papin S, Duquesnoy P, Cazeneuve C, Pantel J, Coppey-Moisan M, Dargemont C, Amselem S (2000) Alternative splicing at the MEFV locus involved in familial Mediterranean fever regulates translocation of the marenostrin/pyrin protein to the nucleus. Hum Mol Genet 9:3001–3009

    Article  CAS  PubMed  Google Scholar 

  26. Booth DR, Lachmann HJ, Gillmore JD, Booth SE, Hawkins PN (2001) Prevalence and significance of the familial Mediterranean fever gene mutation encoding pyrin Q148. Q J Med 94:527–531

    CAS  Google Scholar 

  27. Migita K, Nakamura T, Maeda Y, Miyashita T, Koga T, Tanaka M, Nakamura M, Komori A, Ishibashi H, Origuchi T, Ida H, Kawasaki E, Yasunami M, Eguchi K (2008) MEFV mutations in Japanese rheumatoid arthritis patients. Clin Exp Rheumatol 26:1091–1094

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was funded by the supporting program of the Ministry of Human Resource of China Oversea Returned scholars.

Author information

Authors and Affiliations

  1. Wuhan Children’s Hospital, No. 100 Hongkong Rd, Jiangan District, Wuhan, People’s Republic of China, 430016

    Xuelian He, Shixiu Kang, Jiangwei Luan, Zhisheng Liu, Wei Yin, Hui Yao, Yan Ding & Tao Li

  2. Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Proteos Building, 61 Biopolis Drive, Singapore, 138673, Singapore

    Hao Lu

  3. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore

    Chew-Kiat Heng

Authors
  1. Xuelian He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hao Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shixiu Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiangwei Luan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhisheng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wei Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hui Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yan Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Chew-Kiat Heng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xuelian He.

Rights and permissions

Reprints and permissions

About this article

Cite this article

He, X., Lu, H., Kang, S. et al. MEFV E148Q polymorphism is associated with Henoch–Schönlein purpura in Chinese children. Pediatr Nephrol 25, 2077–2082 (2010). https://doi.org/10.1007/s00467-010-1582-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-010-1582-2

Keywords

Search

Navigation