Advertisement

Archives of Dermatological Research

, Volume 303, Issue 1, pp 19–27 | Cite as

TNFα gene polymorphisms in the pathogenesis of acne vulgaris

  • Kornélia Szabó
  • Gábor Tax
  • Dragos Teodorescu-Brinzeu
  • Andrea Koreck
  • Lajos Kemény
Original Paper

Abstract

Inflammation plays an important role in acne pathogenesis, and pro-inflammatory cytokines are key factors in these events. Tumor necrosis factor alpha (TNFα) is a central molecule coded by a gene that shows high level of genetic polymorphisms especially in its promoter region. Single nucleotide polymorphisms (SNPs) of the TNFα gene have been shown to be associated with an increased risk to develop chronic inflammatory diseases. In order to find out if known TNFα regulatory SNPs (−1031T>C, −857C>T, −863C>A, −308G>A, −238G>A) have a role in the development of the inflammatory reactions in acne vulgaris, we analyzed our genomic collection in a retrospective case–control study using the PCR–RFLP method, and we compared the resulting genotype and allele frequencies. There were no significant differences in the observed genotype or allele frequencies between the control and acne group in case of the −1031, −863, −238 SNPs; however, the TNFα −857 minor T allele was found to act as a protective factor in our study population in acne, and a higher occurrence of the minor −308 A allele in female acne patients was also noted. Genetic variants of the TNFα gene may affect the risk of acne vulgaris. Our results can help to elucidate the molecular events leading to acne development.

Keywords

Acne vulgaris Tumor necrosis factor alpha (TNFα) Single nucleotide polymorphism −857C>T −308G>A 

Notes

Acknowledgments

The authors wish to thank Tanácsné Bajkán Andrea for her excellent technical assistance, Viharosné Dósa-Rácz Éva for the statistical analysis, and Gyimesi Andrea for the help during the preparation of the manuscript. K.Sz. was funded by OTKA PD 73485 Grant.

Conflict of interest statement

The authors state no conflict of interest.

Supplementary material

403_2010_1050_MOESM1_ESM.jpeg (3.8 mb)
Online Resource 1 (JPEG 3913 kb)
403_2010_1050_MOESM2_ESM.doc (53 kb)
Online Resource 2 (DOC 53 kb)
403_2010_1050_MOESM3_ESM.jpeg (2.2 mb)
Online Resource 3 (JPEG 2299 kb)

References

  1. 1.
    Akamatsu H, Komura J, Miyachi Y, Asada Y, Niwa Y (1990) Suppressive effects of linoleic acid on neutrophil oxygen metabolism and phagocytosis. J Invest Dermatol 95:271–274CrossRefPubMedGoogle Scholar
  2. 2.
    Ando I, Kukita A, Soma G, Hino H (1998) A large number of tandem repeats in the polymorphic epithelial mucin gene is associated with severe acne. J Dermatol 25:150–152PubMedGoogle Scholar
  3. 3.
    Barker JN, Mitra RS, Griffiths CE, Dixit VM, Nickoloff BJ (1991) Keratinocytes as initiators of inflammation. Lancet 337:211–214CrossRefPubMedGoogle Scholar
  4. 4.
    Bataille V, Snieder H, MacGregor AJ, Sasieni P, Spector TD (2002) The influence of genetics and environmental factors in the pathogenesis of acne: a twin study of acne in women. J Invest Dermatol 119:1317–1322CrossRefPubMedGoogle Scholar
  5. 5.
    Baz K, Emin EM, Yazici AC, Soylemez F, Guvenc U, Tasdelen B et al (2008) Association between tumor necrosis factor-alpha gene promoter polymorphism at position −308 and acne in Turkish patients. Arch Dermatol Res 300:371–376CrossRefPubMedGoogle Scholar
  6. 6.
    Csato M, Kenderessy AS, Judak R, Dobozy A (1990) Inflammatory mediators are involved in the Candida albicans killing activity of human epidermal cells. Arch Dermatol Res 282:348–350CrossRefPubMedGoogle Scholar
  7. 7.
    Cunliffe WJ, Holland DB, Clark SM, Stables GI (2000) Comedogenesis: some new aetiological, clinical and therapeutic strategies. Br J Dermatol 142:1084–1091CrossRefPubMedGoogle Scholar
  8. 8.
    D’Alfonso S, Richiardi PM (1994) A polymorphic variation in a putative regulation box of the TNFA promoter region. Immunogenetics 39:150–154PubMedGoogle Scholar
  9. 9.
    Emonts M, Hazelzet JA, de Groot R, Hermans PW (2003) Host genetic determinants of Neisseria meningitidis infections. Lancet Infect Dis 3:565–577CrossRefPubMedGoogle Scholar
  10. 10.
    Ferguson LR, Huebner C, Petermann I, Gearry RB, Barclay ML, Demmers P et al (2008) Single nucleotide polymorphism in the tumor necrosis factor-alpha gene affects inflammatory bowel diseases risk. World J Gastroenterol 14:4652–4661CrossRefPubMedGoogle Scholar
  11. 11.
    Fidder HH, Heijmans R, Chowers Y, Bar-Meir S, Avidan B, Pena AS et al (2006) TNF-857 polymorphism in Israeli Jewish patients with inflammatory bowel disease. Int J Immunogenet 33:81–85CrossRefPubMedGoogle Scholar
  12. 12.
    Freedberg IM, Tomic-Canic M, Komine M, Blumenberg M (2001) Keratins and the keratinocyte activation cycle. J Invest Dermatol 116:633–640CrossRefPubMedGoogle Scholar
  13. 13.
    Goto H (2003) Helicobacter pylori and gastric diseases. Nagoya J Med Sci 66:77–85PubMedGoogle Scholar
  14. 14.
    Goulden V, McGeown CH, Cunliffe WJ (1999) The familial risk of adult acne: a comparison between first-degree relatives of affected and unaffected individuals. Br J Dermatol 141:297–300CrossRefPubMedGoogle Scholar
  15. 15.
    Graham GM, Farrar MD, Cruse-Sawyer JE, Holland KT, Ingham E (2004) Proinflammatory cytokine production by human keratinocytes stimulated with Propionibacterium acnes and P. acnes GroEL. Br J Dermatol 150:421–428CrossRefPubMedGoogle Scholar
  16. 16.
    He L, Yang Z, Yu H, Cheng B, Tang W, Dong Y et al (2006) The relationship between CYP17–34T/C polymorphism and acne in Chinese subjects revealed by sequencing. Dermatology 212:338–342CrossRefPubMedGoogle Scholar
  17. 17.
    Herrmann SM, Ricard S, Nicaud V, Mallet C, Arveiler D, Evans A et al (1998) Polymorphisms of the tumour necrosis factor-alpha gene, coronary heart disease and obesity. Eur J Clin Invest 28:59–66CrossRefPubMedGoogle Scholar
  18. 18.
    Higuchi T, Seki N, Kamizono S, Yamada A, Kimura A, Kato H et al (1998) Polymorphism of the 5′-flanking region of the human tumor necrosis factor (TNF)-alpha gene in Japanese. Tissue Antigens 51:605–612CrossRefPubMedGoogle Scholar
  19. 19.
    Hoogendoorn B, Coleman SL, Guy CA, Smith K, Bowen T, Buckland PR et al (2003) Functional analysis of human promoter polymorphisms. Hum Mol Genet 12:2249–2254CrossRefPubMedGoogle Scholar
  20. 20.
    Ingham E, Eady EA, Goodwin CE, Cove JH, Cunliffe WJ (1992) Pro-inflammatory levels of interleukin-1 alpha-like bioactivity are present in the majority of open comedones in acne vulgaris. J Invest Dermatol 98:895–901CrossRefPubMedGoogle Scholar
  21. 21.
    Jiang L, He B, Zhao MW, Ning LD, Li XY, Yao WZ (2005) Association of gene polymorphisms of tumour necrosis factor-alpha and interleukin-13 with chronic obstructive pulmonary disease in Han nationality in Beijing. Chin Med J (Engl) 118:541–547Google Scholar
  22. 22.
    Kato T, Honda M, Kuwata S, Juji T, Fukuda M, Honda Y, Kato N (1999) A search for a mutation in the tumour necrosis factor-alpha gene in narcolepsy. Psychiatry Clin Neurosci 53(3):421–423Google Scholar
  23. 23.
    Kim J (2005) Review of the innate immune response in acne vulgaris: activation of Toll-like receptor 2 in acne triggers inflammatory cytokine responses. Dermatology 211:193–198CrossRefPubMedGoogle Scholar
  24. 24.
    Koreck A, Pivarcsi A, Dobozy A, Kemeny L (2003) The role of innate immunity in the pathogenesis of acne. Dermatology 206:96–105CrossRefPubMedGoogle Scholar
  25. 25.
    Kroeger KM, Carville KS, Abraham LJ (1997) The -308 tumor necrosis factor-alpha promoter polymorphism effects transcription. Mol Immunol 34:391–399CrossRefPubMedGoogle Scholar
  26. 26.
    Miyachi Y, Yoshioka A, Imamura S, Niwa Y (1986) Effect of antibiotics on the generation of reactive oxygen species. J Invest Dermatol 86:449–453CrossRefPubMedGoogle Scholar
  27. 27.
    Murphy JE, Robert C, Kupper TS (2000) Interleukin-1 and cutaneous inflammation: a crucial link between innate and acquired immunity. J Invest Dermatol 114:602–608CrossRefPubMedGoogle Scholar
  28. 28.
    Nagy I, Pivarcsi A, Koreck A, Szell M, Urban E, Kemeny L (2005) Distinct strains of Propionibacterium acnes induce selective human beta-defensin-2 and interleukin-8 expression in human keratinocytes through toll-like receptors. J Invest Dermatol 124:931–938CrossRefPubMedGoogle Scholar
  29. 29.
    Nickoloff BJ, Turka LA (1993) Keratinocytes: key immunocytes of the integument. Am J Pathol 143:325–331PubMedGoogle Scholar
  30. 30.
    Paraskevaidis A, Drakoulis N, Roots I, Orfanos CE, Zouboulis CC (1998) Polymorphisms in the human cytochrome P-450 1A1 gene (CYP1A1) as a factor for developing acne. Dermatology 196:171–175CrossRefPubMedGoogle Scholar
  31. 31.
    Plewig G, Fulton JE, Kligman AM (1971) Cellular dynamics of comedo formation in acne vulgaris. Arch Dermatol Forsch 242:12–29CrossRefPubMedGoogle Scholar
  32. 32.
    Pochi PE, Strauss JS (1969) Sebaceous gland response in man to the administration of testosterone, delta-4-androstenedione, and dehydroisoandrosterone. J Invest Dermatol 52:32–36PubMedGoogle Scholar
  33. 33.
    Pomerantz JL, Baltimore D (2002) Two pathways to NF-kappaB. Mol Cell 10:693–695CrossRefPubMedGoogle Scholar
  34. 34.
    Roxo VM, Pereira NF, Pavoni DP, Lin MT, Hansen JA, de Poersch O et al (2003) Polymorphisms within the tumor necrosis factor and lymphotoxin-alpha genes and endemic pemphigus foliaceus—are there any associations? Tissue Antigens 62:394–400CrossRefPubMedGoogle Scholar
  35. 35.
    Simmonds MJ, Heward JM, Howson JM, Foxall H, Nithiyananthan R, Franklyn JA et al (2004) A systematic approach to the assessment of known TNF-alpha polymorphisms in Graves’ disease. Genes Immun 5:267–273CrossRefPubMedGoogle Scholar
  36. 36.
    Skoog T, van't Hooft FM, Kallin B, Jovinge S, Boquist S, Nilsson J, Eriksson P, Hamsten A (1999) A common functional polymorphism (C-->A substitution at position -863) in the promoter region of the tumour necrosis factor-alpha (TNF-alpha) gene associated with reduced circulating levels of TNF-alpha. Hum Mol Genet 8(8):1443–1449Google Scholar
  37. 37.
    Sobjanek M, Zablotna M, Nedoszytko B, Sokolowska-Wojdylo M, Wlodarkiewicz A (2009) Lack of association between the promoter polymorphisms at positions −238 and −308 of the tumour necrosis factor alpha gene and acne vulgaris in Polish patients. J Eur Acad Dermatol Venereol 23:331–332CrossRefPubMedGoogle Scholar
  38. 38.
    Soga Y, Nishimura F, Ohyama H, Maeda H, Takashiba S, Murayama Y (2003) Tumor necrosis factor-alpha gene (TNF-alpha) -1031/-863, -857 single-nucleotide polymorphisms (SNPs) are associated with severe adult periodontitis in Japanese. J Clin Periodontol 30(6):524–531Google Scholar
  39. 39.
    Takeuchi O, Hoshino K, Kawai T, Sanjo H, Takada H, Ogawa T, Takeda K, Akira S (1999) Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity 11:443–451CrossRefPubMedGoogle Scholar
  40. 40.
    van Heel DA, Udalova IA, De Silva AP, McGovern DP, Kinouchi Y, Hull J, Lench NJ, Cardon LR, Carey AH, Jewell DP, Kwiatkowski D (2002) Inflammatory bowel disease is associated with a TNF polymorphism that affects an interaction between the OCT1 and NF(-kappa)B transcription factors. Hum Mol Genet 11:1281–1289CrossRefPubMedGoogle Scholar
  41. 41.
    Waldron-Lynch F, Adams C, Shanahan F, Molloy MG, O’Gara F (1999) Genetic analysis of the 3′ untranslated region of the tumour necrosis factor shows a highly conserved region in rheumatoid arthritis affected and unaffected subjects. J Med Genet 36:214–216PubMedGoogle Scholar
  42. 42.
    Waldron-Lynch F, Adams C, Amos C, Zhu DK, McDermott MF, Shanahan F et al (2001) Tumour necrosis factor 5′ promoter single nucleotide polymorphisms influence susceptibility to rheumatoid arthritis (RA) in immunogenetically defined multiplex RA families. Genes Immun 2(2):82–87Google Scholar
  43. 43.
    Webster GF, Leyden JJ, Tsai CC, Baehni P, McArthur WP (1980) Polymorphonuclear leukocyte lysosomal release in response to Propionibacterium acnes in vitro and its enhancement by sera from inflammatory acne patients. J Invest Dermatol 74:398–401CrossRefPubMedGoogle Scholar
  44. 44.
    Wilschanski M, Schlesinger Y, Faber J, Rudensky B, Ohnona FS, Freier S, Rahman E, Refael S, Halle D (2007) Combination of Helicobacter pylori strain and tumor necrosis factor-alpha polymorphism of the host increases the risk of peptic ulcer disease in children. J Pediatr Gastroenterol Nutr 45:199–203Google Scholar
  45. 45.
    Wilson AG, di Giovine FS, Blakemore AI, Duff GW (1992) Single base polymorphism in the human tumour necrosis factor alpha (TNF alpha) gene detectable by NcoI restriction of PCR product. Hum Mol Genet 1(5):353Google Scholar
  46. 46.
    Wilson AG, di Giovine FS, Blakemore AIF, Duff GW (1997a) Single base polymorphism in the human tumor necrosis alpha promoter on transcriptional activation. Proc Natl Acad Sci USA 94:3195CrossRefPubMedGoogle Scholar
  47. 47.
    Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW (1997b) Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci UA 94:3195–3199CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Kornélia Szabó
    • 1
    • 2
  • Gábor Tax
    • 2
  • Dragos Teodorescu-Brinzeu
    • 4
  • Andrea Koreck
    • 2
    • 3
  • Lajos Kemény
    • 1
    • 2
  1. 1.Dermatological Research Group of the Hungarian Academy of SciencesSzegedHungary
  2. 2.Department of Dermatology and Allergology, Albert Szent-Györgyi Medical and Pharmaceutical CenterUniversity of SzegedSzegedHungary
  3. 3.Department of ImmunologyVictor Babes University TimisoaraTimisoaraRomania
  4. 4.Department of DermatologyVictor Babes University TimisoaraTimisoaraRomania

Personalised recommendations