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Investigative Report

Platelet-derived Growth Factor Receptor Alpha Gene Mutations in Vitiligo Vulgaris

doi: 10.2340/00015555-0820

Abstract:

Vitiligo vulgaris is an acquired depigmenting disorder resulting from the loss of melanocytes in the skin. Though several putative susceptibility loci of vitiligo have been identified in different populations, the patho­genesis of the disease remains poorly understood.
Through genetic linkage analysis of a large Chinese family cohort of vitiligo, we identified a vitiligo linkage locus AIS4 within chromosome 4q12-q21, a region containing several possible candidate genes, including the platelet-derived growth factor receptor alpha (PDGFRA) gene. We postulated that PDGFR mutations may be linked with vitiligo. To test this hypothesis, we performed DNA sequencing on this gene in 143 multiplex families with familial vitiligo vulgaris, 480 patients with sporadic vitiligo vulgaris, and 480 healthy subjects. Mutations were found in 3.5% of familial vitiligo cases, which is significantly higher than for the general population (0.42%, p = 0.008, Fisher’s exact test), and possibly higher than in sporadic vitiligo patients (1.0%, p = 0.053). To our knowledge, this is the first observation that PDGFRA mutations are linked with familial vitiligo vulgaris.

Authors:

Shengxin Xu, Youwen Zhou, Sen Yang, Yunqing Ren, Chi Zhang, Cheng Quan, Min Gao, Caifeng He, Hui Chen, Jianwen Hhan, Jianjun Chen, Yanhua Liang, Jianqiang Yang, Liangdan Sun, Xianyong Yin, Jianjun Liu, Xuejun Zhang

References

  • Hann SK, Nordlund J. Vitiligo: a comprehensive monograph on basic and clinical science. New York: Blackwell Science, 2000.
  • Hofmann UB, Brocker EB, Hamm H. Simultaneous onset of segmental vitiligo and a halo surrounding a congenital melanocytic naevus. Acta Derm Venereol 2009; 89: 402–406.
  • Yalcin B, Tamer E, Gur G, Oztas P, Polat MU, Alli N. Neurofibromatosis 1/Noonan syndrome associated with Hashimoto’s thyroiditis and vitiligo. Acta Derm Venereol 2006; 86: 80–81.
  • Hafez M, Sharaf L, Abd el-Nabi SM. The genetics of vitiligo. Acta Derm Venereol 1983; 63: 249–251.
  • Pehlivan S, Ozkinay F, Alper S, Onay H, Yuksel E, Pehlivan M, et al. Association between IL4 (-590), ACE (I)/(D), CCR5 (Delta32), CTLA4 (+49) and IL1-RN (VNTR in intron 2) gene polymorphisms and vitiligo. Eur J Dermatol 2009; 19: 126–128.
  • Li M, Gao Y, Li C, Liu L, Li K, Gao L, et al. Association of COX2 functional polymorphisms and the risk of vitiligo in Chinese populations. J Dermatol Sci 2009; 53: 176–181.
  • Birlea SA, Laberge GS, Procopciuc LM, Fain PR, Spritz RA. CTLA4 and generalized vitiligo: two genetic association studies and a meta-analysis of published data. Pigment Cell Melanoma Res 2009; 22: 230–234.
  • Ren Y, Yang S, Xu S, Gao M, Huang W, Gao T, et al. Genetic variation of promoter sequence modulates XBP1 expression and genetic risk for vitiligo. PLoS Genet 2009; 5: e1000523.
  • Zhang XJ, Chen JJ, Liu JB. The genetic concept of vitiligo. J Dermatol Sci 2005; 39: 137–146.
  • Chen JJ, Huang W, Gui JP, Yang S, Zhou FS, Xiong QG, et al. A novel linkage to generalized vitiligo on 4q13-q21 identified in a genomewide linkage analysis of Chinese families. Am J Hum Genet 2005; 76: 1057–1065.
  • Mol CD, Lim KB, Sridhar V, Zou H, Chien EY, Sang BC, et al. Structure of a c-kit product complex reveals the basis for kinase transactivation. J Biol Chem 2003; 278: 31461–31464.
  • Gruneberg H, Truslove GM. Two closely linked genes in the mouse. Genet Res 1960; 1: 69–90.
  • Legros L, Cassuto JP, Ortonne JP. Imatinib mesilate (Glivec): a systemic depigmenting agent for extensive vitiligo? Br J Dermatol 2005; 153: 691–692.
  • Adameyko I, Lallemend F, Aquino JB, Pereira JA, Topilko P, Muller T, et al. Schwann cell precursors from nerve innervation are a cellular origin of melanocytes in skin. Cell 2009; 139: 366–379.
  • Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.
  • Kawagishi J, Kumabe T, Yoshimoto T, Yamamoto T. Structure, organization, and transcription units of the human alpha-platelet-derived growth factor receptor gene, PDGFRA. Genomics 1995; 30: 224–232.
  • Yu JC, Li W, Wang LM, Uren A, Pierce JH, Heidaran MA. Differential requirement of a motif within the carboxyl-terminal domain of alpha-platelet-derived growth factor (alpha PDGF) receptor for PDGF focus forming activity chemotaxis, or growth. J Biol Chem 1995; 270: 7033–7036.
  • Raanani P, Goldman JM, Ben-Bassat I. Challenges in oncology. Case 3. Depigmentation in a chronic myeloid leukemia patient treated with STI-571. J Clin Oncol 2002; 20: 869–870.
  • Hasan S, Dinh K, Lombardo F, Dawkins F, Kark J. Hypopigmentation in an African patient treated with imatinib mesylate: a case report. J Natl Med Assoc 2003; 95: 722–724.
  • Tsao AS, Kantarjian H, Cortes J, O’Brien S, Talpaz M. Imatinib mesylate causes hypopigmentation in the skin. Cancer 2003; 98: 2483–2487.
  • Brazzelli V, Roveda E, Prestinari F, Barbagallo T, Bellani E, Trevisan V, et al. Vitiligo-like lesions and diffuse lightening of the skin in a pediatric patient treated with imatinib mesylate: a noninvasive colorimetric assessment. Pediatr Dermatol 2006; 23: 175–178.
  • Boissy RE, Liu YY, Medrano EE, Nordlund JJ. Structural aberration of the rough endoplasmic reticulum and melanosome compartmentalization in long-term cultures of melanocytes from vitiligo patients. J Invest Dermatol 1991; 97: 395–404.
  • Boissy RE, Beato KE, Nordlund JJ. Dilated rough endoplasmic reticulum and premature death in melanocytes cultured from the vitiligo mouse. Am J Pathol 1991; 138: 1511–1525.
  • Wankowicz-Kalinska A, Le Poole C, van den Wijngaard R, Storkus WJ, Das PK. Melanocyte-specific immune response in melanoma and vitiligo: two faces of the same coin? Pigment Cell Res 2003; 16: 254–260.
  • Lerner AB, Nordlund JJ. Vitiligo: the loss of pigment in skin, hair and eyes. J Dermatol 1978; 5: 1–8.
  • Koga M. Vitiligo: a new classification and therapy. Br J Dermatol 1977; 97: 255–261.
  • Chakravarti A. Population genetics – making sense out of sequence. Nat Genet 1999; 21: 56–60.
  • Lander ES. The new genomics: global views of biology. Science 1996; 274: 536–539.
  • Zhang XJ, Huang W, Yang S, Sun LD, Zhang FY, Zhu QX, et al. Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nat Genet 2009; 41: 205–210.
  • Cargill M, Schrodi SJ, Chang M, Garcia VE, Brandon R, Callis KP, et al. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 2007; 80: 273–290.
  • Musone SL, Taylor KE, Lu TT, Nititham J, Ferreira RC, Ortmann W, et al. Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus. Nat Genet 2008; 40: 1062–1064.
  • Graham RR, Cotsapas C, Davies L, Hackett R, Lessard CJ, Leon JM, et al. Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. Nat Genet 2008; 40: 1059–1061.
  • Lee-Kirsch MA, Gong M, Chowdhury D, Senenko L, Engel K, Lee YA, et al. Mutations in the gene encoding the 3’-5’ DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Nat Genet 2007; 39: 1065–1067.
  • Polychronakos C. Common and rare alleles as causes of complex phenotypes. Curr Atheroscler Reports 2008; 10: 194–200.
  • Yang C-F, Hwu W-L, Yang L-C, Chung W-H, Chien Y-H, Hung C-F, et al. A Promoter Sequence Variant of ZNF750 Is Linked with Familial Psoriasis. J Invest Dermatol 2008; 128: 1662–1668.
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    Volume 90, Issue 2

    DOI: 10.2340/00015555-0820

    Pages: 131-135

    View at PubMed