Ann Dermatol.  2014 Jun;26(3):343-348.

Association of CYP2C9 Genetic Variants with Vitiligo

Affiliations
  • 1Department of Dermatology, College of Medicine, Qassim University, Buraidah, Saudi Arabia. azolibani@yahoo.com
  • 2Department of Dermatology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
  • 3Research Centre, College of Medicine, Qassim University, Buraidah, Saudi Arabia.

Abstract

BACKGROUND
Vitiligo is a depigmenting skin disorder in which genetic factors play an important role.
OBJECTIVE
To examine the association of CYP2C9 *1/*2/*3 gene polymorphism with vitiligo.
METHODS
In this case controlled study, 95 Saudi patients with vitiligo (50 men and 45 women), with a mean age of 27.3 years, were analyzed. Patients were compared to 86 healthy controls from the same locality (76 men and 10 women), with a mean age of 20.1 years. In all participants, DNA was extracted and processed for characterization of 2C9 *1/*2/*3 gene variants using real time-polymerase chain reaction.
RESULTS
Vitiligo patients have a significantly higher CYP2C9 *3 allele carriage rate compared to controls (32.7% versus 4.7%, p=0.00, odds ratio=9.9, 95% confidence interval=3.3~29.6). On the other hand, frequencies of CYP2C9 *2 genotypes and alleles did not show any significant difference between vitiligo cases and controls. When the frequencies of CYP2C9 genotypes were compared among subgroups of age, gender, family history, and disease patterns, the cases with positive consanguinity had significantly higher frequencies of homozygous genotypes than others (p=0.029).
CONCLUSION
CYP2C9 *3 allele carriage is probably associated with vitiligo susceptibility.

Keyword

CYP2C9; Genetic polymorphism; Vitiligo

MeSH Terms

Alleles
Case-Control Studies
Consanguinity
DNA
Genotype
Hand
Humans
Male
Polymorphism, Genetic
Skin
Vitiligo*
DNA

Reference

1. Grimes PE. New insights and new therapies in vitiligo. JAMA. 2005; 293:730–735.
Article
2. van den Wijngaard R, Wankowicz-Kalinska A, Le Poole C, Tigges B, Westerhof W, Das P. Local immune response in skin of generalized vitiligo patients. Destruction of melanocytes is associated with the prominent presence of CLA+ T cells at the perilesional site. Lab Invest. 2000; 80:1299–1309.
Article
3. Ongenae K, Van Geel N, Naeyaert JM. Evidence for an autoimmune pathogenesis of vitiligo. Pigment Cell Res. 2003; 16:90–100.
Article
4. Kemp EH, Waterman EA, Hawes BE, O'Neill K, Gottumukkala RV, Gawkrodger DJ, et al. The melanin-concentrating hormone receptor 1, a novel target of autoantibody responses in vitiligo. J Clin Invest. 2002; 109:923–930.
Article
5. Majumder PP, Nordlund JJ, Nath SK. Pattern of familial aggregation of vitiligo. Arch Dermatol. 1993; 129:994–998.
Article
6. Handa S, Kaur I. Vitiligo: clinical findings in 1436 patients. J Dermatol. 1999; 26:653–657.
Article
7. O'Sullivan JJ, Stevenson CJ. Screening for occupational vitiligo in workers exposed to hydroquinone monomethyl ether and to paratertiary-amyl-phenol. Br J Ind Med. 1981; 38:381–383.
8. Schallreuter KU, Wood JM. Free radical reduction in the human epidermis. Free Radic Biol Med. 1989; 6:519–532.
Article
9. Bièche I, Narjoz C, Asselah T, Vacher S, Marcellin P, Lidereau R, et al. Reverse transcriptase-PCR quantification of mRNA levels from cytochrome (CYP)1, CYP2 and CYP3 families in 22 different human tissues. Pharmacogenet Genomics. 2007; 17:731–742.
Article
10. Orellana M, Guajardo V. Cytochrome P450 activity and its alteration in different diseases. Rev Med Chil. 2004; 132:85–94.
11. Spiecker M, Darius H, Hankeln T, Soufi M, Sattler AM, Schaefer JR, et al. Risk of coronary artery disease associated with polymorphism of the cytochrome P450 epoxygenase CYP2J2. Circulation. 2004; 110:2132–2136.
Article
12. Hoffmann MM, Bugert P, Seelhorst U, Wellnitz B, Winkelmann BR, Boehm BO, et al. The -50G>T polymorphism in the promoter of the CYP2J2 gene in coronary heart disease: the Ludwigshafen Risk and Cardiovascular Health study. Clin Chem. 2007; 53:539–540.
Article
13. Delozier TC, Kissling GE, Coulter SJ, Dai D, Foley JF, Bradbury JA, et al. Detection of human CYP2C8, CYP2C9, and CYP2J2 in cardiovascular tissues. Drug Metab Dispos. 2007; 35:682–688.
Article
14. Boxenbaum H. Cytochrome P450 3A4 in vivo ketoconazole competitive inhibition: determination of Ki and dangers associated with high clearance drugs in general. J Pharm Pharm Sci. 1999; 2:47–52.
15. Gras J, Llenas J. Effects of H1 antihistamines on animal models of QTc prolongation. Drug Saf. 1999; 21:Suppl 1. 39–44. discussion 81-87.
Article
16. Sanderson S, Emery J, Higgins J. CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: a HuGEnet systematic review and meta-analysis. Genet Med. 2005; 7:97–104.
Article
17. Burian M, Grösch S, Tegeder I, Geisslinger G. Validation of a new fluorogenic real-time PCR assay for detection of CYP2C9 allelic variants and CYP2C9 allelic distribution in a German population. Br J Clin Pharmacol. 2002; 54:518–521.
Article
18. Veenstra DL, Blough DK, Higashi MK, Farin FM, Srinouanprachan S, Rieder MJ, et al. CYP2C9 haplotype structure in European American warfarin patients and association with clinical outcomes. Clin Pharmacol Ther. 2005; 77:353–364.
Article
19. Hercogová J, Schwartz RA, Lotti TM. Classification of vitiligo: a challenging endeavor. Dermatol Ther. 2012; 25:Suppl 1. S10–S16.
Article
20. Enayetallah AE, French RA, Thibodeau MS, Grant DF. Distribution of soluble epoxide hydrolase and of cytochrome P450 2C8, 2C9, and 2J2 in human tissues. J Histochem Cytochem. 2004; 52:447–454.
Article
21. Schallreuter KU, Wood JM, Berger J. Low catalase levels in the epidermis of patients with vitiligo. J Invest Dermatol. 1991; 97:1081–1085.
Article
22. Maresca V, Roccella M, Roccella F, Camera E, Del Porto G, Passi S, et al. Increased sensitivity to peroxidative agents as a possible pathogenic factor of melanocyte damage in vitiligo. J Invest Dermatol. 1997; 109:310–313.
Article
23. Dell'Anna ML, Maresca V, Briganti S, Camera E, Falchi M, Picardo M. Mitochondrial impairment in peripheral blood mononuclear cells during the active phase of vitiligo. J Invest Dermatol. 2001; 117:908–913.
24. Giovannelli L, Bellandi S, Pitozzi V, Fabbri P, Dolara P, Moretti S. Increased oxidative DNA damage in mononuclear leukocytes in vitiligo. Mutat Res. 2004; 556:101–106.
Article
25. Hashemi-Soteh SM, Shahabi-Majd N, Gholizadeh AR, Shiran MR. Allele and genotype frequencies of CYP2C9 within an Iranian population (Mazandaran). Genet Test Mol Biomarkers. 2012; 16:817–821.
Article
26. Xie HG, Prasad HC, Kim RB, Stein CM. CYP2C9 allelic variants: ethnic distribution and functional significance. Adv Drug Deliv Rev. 2002; 54:1257–1270.
Article
27. Rathore SS, Agarwal SK, Pande S, Mittal T, Mittal B. Frequencies of VKORC1 -1639 G>A, CYP2C9*2 and CYP2C9*3 genetic variants in the Northern Indian population. Biosci Trends. 2010; 4:333–337.
28. Lee HW, Lim MS, Lee J, Jegal MY, Kim DW, Lee WK, et al. Frequency of CYP2C9 variant alleles, including CYP2C9*13 in a Korean population and effect on glimepiride pharmacokinetics. J Clin Pharm Ther. 2012; 37:105–111.
Article
29. Yang ZF, Cui HW, Hasi T, Jia SQ, Gong ML, Su XL. Genetic polymorphisms of cytochrome P450 enzymes 2C9 and 2C19 in a healthy Mongolian population in China. Genet Mol Res. 2010; 9:1844–1851.
Article
30. Scibona P, Redal MA, Garfi LG, Arbelbide J, Argibay PF, Belloso WH. Prevalence of CYP2C9 and VKORC1 alleles in the Argentine population and implications for prescribing dosages of anticoagulants. Genet Mol Res. 2012; 11:70–76.
Article
31. Schallreuter KU, Moore J, Wood JM, Beazley WD, Gaze DC, Tobin DJ, et al. In vivo and in vitro evidence for hydrogen peroxide (H2O2) accumulation in the epidermis of patients with vitiligo and its successful removal by a UVB-activated pseudocatalase. J Investig Dermatol Symp Proc. 1999; 4:91–96.
Article
32. Schallreuter KU, Moore J, Wood JM, Beazley WD, Peters EM, Marles LK, et al. Epidermal H(2)O(2) accumulation alters tetrahydrobiopterin (6BH4) recycling in vitiligo: identification of a general mechanism in regulation of all 6BH4-dependent processes? J Invest Dermatol. 2001; 116:167–174.
Article
33. Jin Y, Birlea SA, Fain PR, Ferrara TM, Ben S, Riccardi SL, et al. Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo. Nat Genet. 2012; 44:676–680.
Article
34. Tang XF, Zhang Z, Hu DY, Xu AE, Zhou HS, Sun LD, et al. Association analyses identify three susceptibility Loci for vitiligo in the Chinese Han population. J Invest Dermatol. 2013; 133:403–410.
Article
35. Tang J, Liu JL, Zhang C, Hu da Y, He SM, Zuo XB, et al. The association between a single nucleotide polymorphism rs11966200 in MHC region and clinical features of generalized vitiligo in Chinese Han population. Mol Biol Rep. 2013; 40:4097–4100.
Article
36. Weise A, Prause S, Eidens M, Weber MM, Kann PH, Forst T, et al. Prevalence of CYP450 gene variations in patients with type 2 diabetes. Clin Lab. 2010; 56:311–318.
37. Pedersen RS, Brasch-Andersen C, Sim SC, Bergmann TK, Halling J, Petersen MS, et al. Linkage disequilibrium between the CYP2C19*17 allele and wildtype CYP2C8 and CYP2C9 alleles: identification of CYP2C haplotypes in healthy Nordic populations. Eur J Clin Pharmacol. 2010; 66:1199–1205.
Article
38. Semiz S, Dujic T, Ostanek B, Prnjavorac B, Bego T, Malenica M, et al. Analysis of CYP2C9*2, CYP2C19*2, and CYP2D6*4 polymorphisms in patients with type 2 diabetes mellitus. Bosn J Basic Med Sci. 2010; 10:287–291.
Article
39. Kaur-Knudsen D, Bojesen SE, Nordestgaard BG. Cytochrome P450 1B1 and 2C9 genotypes and risk of ischemic vascular disease, cancer, and chronic obstructive pulmonary disease. Curr Vasc Pharmacol. 2012; 10:512–520.
Article
40. Liu Y, Zhong SL, Tan HH, Yang M, Fei HW, Yu XY, et al. Impact of CYP2C9 and VKORC1 polymorphism on warfarin response during initiation of therapy. Zhonghua Xin Xue Guan Bing Za Zhi. 2011; 39:929–935.
Full Text Links
  • AD
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr