Association study between polymorphisms of CD28, CTLA4 and ICOS and non-segmental vitiligo in a Korean population

Abstract

Abstract. CD28 molecule (CD28), cytotoxic T-lymphocyteassociated protein 4 (CTLA4) and inducible T-cell co-stimulator (ICOS) are important regulators of the immune system. Vitiligo, a common autoimmune skin disorder, is characterized by a loss of melanocytes that results in cutaneous white patches. The aim of the present study was to determine whether or not polymorphisms of the CD28, CTLA4 and ICOS genes are associated with non-segmental vitiligo in a Korean population. To determine the relationships between CD28, CTLA4 and ICOS genes and vitiligo, four single nucleotide polymorphisms (SNPs) associated with the CD28 gene [rs1879877 (promoter, -1198), rs3181097 (promoter, -1059), rs2140148 (intron 1) and rs3116494 (intron 2)], two SNPs associated with the CTLA4 gene [rs231777 (intron 1) and rs231779 (intron 1)] and five SNPs associated with the ICOS gene [rs4270326 (intron 3), rs11571314 (intron 3), rs10183087 (3' untranslated region; UTR), rs4404254 (3'UTR) and rs1559931 (3'UTR)] were selected. Two hundred and thirty-one patients with non-segmental vitiligo (NSV) and 405 healthy controls were enrolled. Genotyping was performed using the restriction fragment length polymorphism technique and direct sequencing. SNPStats, Haploview 4.2 and SPSS 18.0 were used to conduct the analyses. Significant differences were noted between CTLA4 (p<0.05) and NSV, but not CD28 and ICOS (p>0.05). However, these associations disappeared after Bonferroni correction. The CD28, CTLA4 and ICOS genes may not be associated with NSV.

Modern vitiligo genetics sheds new light on an ancient disease

“…published a comprehensive review of 33 claimed vitiligo candidate genes ( ACE , AIRE , CAT , CD4 , CLEC11A , COMT , CTLA4 , C12orf10 , DDR1 , EDN1 , ESR1 , FAS , FBXO11 , FOXD3 , FOXP3 , GSTM1 , GSTT1 , IL1RN , IL10 , KITLG , MBL2 , NFE2L2 , PDGFRA‐KIT , PTGS2 , STAT4 , TAP1‐PSMB8 , TGFBR2 , TNF , TSLP , TXNDC5 , UVRAG , VDR , XBP1 ), finding support for only three ( TSLP , XBP1 , FOXP3 ) in analysis of a genome‐wide vitiligo GWAS dataset . Additional claimed candidate gene associations with vitiligo include AHR , COX2 , GSTP1 , IL4 , IL19 and IL20RB , INOS , PRO2268 , TLR2 and TLR4 , while candidate genes reported not to be associated include CD28 , ICOS , IL20 , IL24e and IL20RA , MTHFR , and SMOC2 . Some of these claimed novel candidate gene associations may be valid, though most are likely to represent false‐positives.…”

Understanding the Role of Lymphocytes in Vitiligo

“…CD40 ND CD40L were not changed between stable vitiligo and active cases [28,38]. CD28, CTLA4, and ICOS were studied too and although they are important regulators of the immune system yet in vitiligo, no polymorphism or changes were recorded to conclude that the CD28, CTLA4, and ICOS genes may not be associated with NSV [30,48]. A similar experiment was done on melanoma cases with the same outcome [49].…”

“…The increase in the number of CD8+ T cells was significant suggesting that SV also has an autoimmune mechanism. T cells are also involved in early evolving segmental vitiligo [48].…”