Cyclooxygenase-2 (COX2) plays an important role in the production of prostaglandin E2 (PGE2), which is made by epidermal keratinocytes in response to ultraviolet radiation (UVR). PGE2 is important for the proliferation and melanogenesis of epidermal melanocytes, the loss of which leads to vitiligo. COX2-1195A > G, -765G > C, and -8473T > C polymorphisms may influence the mRNA levels of COX2 and affect the production of PGE2 subsequently. Therefore, we supposed that these polymorphisms may be associated with vitiligo.
The aim of the study was to elucidate the association between three functional COX2 polymorphisms and the risk of vitiligo.
This was a hospital-based, case–control study of 755 vitiligo patients and 774 vitiligo-free controls who were frequency matched by age and sex. We genotyped COX2-1195A>G, -765G>C, and -8473T>C polymorphisms by using PCR-restriction fragment length polymorphism (RFLP) method and assessed their respective associations with the risk of vitiligo in Han Chinese populations.
We found a statistically significant increased risk of vitiligo to be associated with the COX2-1195 G variant allele (p = 0.004). Significantly higher vitiligo risks were found among subgroups with these characteristics: age >20 years, male, active, nonsegmental vitiligo, and onset age >20 years. In addition, the interaction between COX2-1195 and COX2-8473 was statistically significant (p = 0.004).
For the first time, we provide evidence that functional polymorphisms in the COX2 gene may influence the risk of vitiligo in Han Chinese populations, suggesting new clues that help to clarify the pathogenesis of vitiligo. Larger studies are needed to verify these findings.
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- Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their families.Pigment Cell Res. 2003; 16: 208-214
- An epidemiological survey for four skin diseases in Anhui.Chin J Dermatol. 2002; 35 ([in Chinese]): 406-407
- Prostaglandin E2 regulates melanocyte dendrite formation through activation of PKCzeta.Exp Cell Res. 2007; 313: 3840-3850
- Epidermal COX2 induction following ultraviolet irradiation: suggested mechanism for the role of COX2 inhibition in photoprotection.J Invest Dermatol. 2003; 121: 853-861
- Prostaglandin metabolism in human hair follicle.Exp Dermatol. 2007; 16: 762-769
- Influence of prostaglandin F2alpha and its analogues on hair regrowth and follicular melanogenesis in a murine model.Exp Dermatol. 2005; 14: 323-328
- Proteinase-activated receptor-2 stimulates prostaglandin production in keratinocytes: analysis of prostaglandin receptors on human melanocytes and effects of PGE2 and PGF2alpha on melanocyte dendricity.J Invest Dermatol. 2004; 122: 1214-1224
- Topical prostaglandin analog (PGE2) in vitiligo—a preliminary study.Int J Dermatol. 2002; 41: 942-945
- Effect of regulated expression of human cyclooxygenase isoforms on eicosanoid and isoeicosanoid production in inflammation.J Clin Invest. 2000; 105: 1473-1482
- Transcription of prostanoid receptor genes and cyclooxygenase enzyme genes in cultivated human iridial melanocytes from eyes of different colours.Pigment Cell Res. 2003; 16: 43-49
- Constitutive expression and localization of Cox-1 and Cox-2 in rabbit iris and ciliary body.Exp Eye Res. 2001; 72: 611-621
- A proposed COX-2 and PGE(2) receptor interaction in UV-exposed mouse skin.Mol Carcinog. 2007; 46: 699-704
- A role for cyclooxygenase-2 in ultraviolet light-induced skin carcinogenesis.Mol Carcinog. 2007; 46: 692-698
- Assignment of the human prostaglandin-endoperoxide synthase 2 (PTGS2) gene to 1q25 by fluorescence in situ hybridization.Genomics. 1994; 23: 718-719
- Identification of functional genetic variants in cyclooxygenase-2 and their association with risk of esophageal cancer.Gastroenterology. 2005; 129: 565-576
- The 3′-untranslated region of murine cyclooxygenase-2 contains multiple regulatory elements that alter message stability and translational efficiency.J Biol Chem. 2001; 276: 23179-23185
- Association of COX-2 gene haplotypes with prostaglandins production in bronchial asthma.J Allergy Clin Immunol. 2005; 116: 221-223
- Clinical predictors of outcome in vitiligo.Indian J Dermatol Venereol Leprol. 2002; 68: 323-325
- Association of prostaglandin-endoperoxide synthase 2 (PTGS2) polymorphisms and Alzheimer's disease in Chinese.Neurobiol Aging. 2007; (Epub ahead of print)
- Polymorphisms of the neuronal and inducible nitric oxide synthase genes and the risk of cutaneous melanoma: a case–control study.Cancer. 2007; 109: 1570-1578
- Polymorphisms in the DNA repair genes XPC, XPD, and XPG and risk of cutaneous melanoma: a case–control analysis.Cancer Epidemiol Biomarkers Prev. 2006; 15: 2526-2532
- Vitiligo in childhood.Med Pregl. 2002; 55: 475-480
- A common polymorphism in the 3’UTR of cyclooxygenase 2/prostaglandin synthase 2 gene and risk of lung cancer in a Chinese population.Lung Cancer. 2005; 48: 11-17
- Common promoter variant in cyclooxygenase-2 represses gene expression: evidence of role in acute-phase inflammatory response.Arterioscler Thromb Vasc Biol. 2002; 22: 1631-1636
- The proximal region of the 3-untranslated region of cyclooxygenase-2 is recognized by a multimeric protein complex containing HuR, TIA-1, TIAR, and the heterogeneous nuclear ribonucleoprotein U.J Biol Chem. 2003; 278: 36157-36162
- Identification of RNA-binding proteins in RAW 264,7 cells that recognize a lipopolysaccharide-responsive element in the 3-untranslated region of the murine cyclooxygenase-2 mRNA.J Biol Chem. 2004; 279: 8196-8205
- Allellic variants in regulatory regions of cyclooxygenase-2: association with advanced colorectal adenoma.Br J Cancer. 2005; 93: 953-959
- Association of a common polymorphism in the cyclooxygenase 2 gene with risk of non-small cell lung cancer.Carcinogenesis. 2004; 25: 229-235
- COX-2 gene promoter haplotypes and prostate cancer risk.Carcinogenesis. 2004; 25: 961-966
- Polymorphisms in COX-2, NSAID use and risk of basal cell carcinoma in a prospective study of Danes.Mutat Res. 2007; 617: 138-146
Published online: July 12, 2010
Accepted: September 25, 2008
Received in revised form: September 20, 2008
Received: July 28, 2008
© 2008 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.