Xianfa Tang1,2,3, Hui Cheng1,2,3, Lu Cheng1,2,3, Bo Liang1,2,3, Mengyun Chen1,2,3, Xiaodong Zheng1,2,3, Fengli Xiao4,5,6. 1. Department of Dermatology and Institute of Dermatology at No. 1 Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China. 2. Key Laboratory of Dermatology, Ministry of Education, Hefei, China. 3. Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, China. 4. Department of Dermatology and Institute of Dermatology at No. 1 Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China. xiaofengli@126.com. 5. Key Laboratory of Dermatology, Ministry of Education, Hefei, China. xiaofengli@126.com. 6. Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, China. xiaofengli@126.com.
Abstract
BACKGROUND: Vitiligo is a complex disease in which patchy depigmentation is the result of an autoimmune-induced loss of melanocytes in affected regions. On the basis of a genome-wide linkage analysis of vitiligo in the Chinese Han population, we previously showed significant evidence of a linkage between 22q12 and vitiligo. Our aim in the current study was to identify vitiligo susceptibility variants within an expanded region of the 22q12 locus. METHODS AND RESULTS: An in-depth analysis of the expanded region of the 22q12 locus was performed by imputation using a large GWAS dataset consisting of 1117 cases and 1701 controls. Eight nominal SNPs were selected and genotyped in an independent cohort of Chinese Han individuals (2069 patients and 1370 control individuals) by using the Sequenom MassArray iPLEX1 system. The data were analyzed with PLINK 1.07 software. The C allele of rs730669 located in ZDHHC8/RTN4R showed a strong association with vitiligo (P = 3.25 × 10-8, OR = 0.81). The C allele of rs4820338 located in VPREB1 and the A allele of rs2051582 (a SNP reported in our previous study) located in IL2RB showed a suggestive association with vitiligo (P = 1.04 × 10-5, OR = 0.86; P = 1.78 × 10-6, OR = 1.27). The three identified SNPs showed independent associations with vitiligo in a conditional logistic regression analysis (all P < 1.0 × 10-5; all D' < 0.05 and r2 < 1.0 × 10-4). CONCLUSIONS: The study reveals that two novel variants rs730669 (ZDHHC8/RTN4R) and rs4820338 (VPREB1) on 22q11.2 might confer susceptibility to vitiligo and affect disease subphenotypes. The presence of multiple independent variants emphasizes their important roles in the genetic pathogenesis of disease.
BACKGROUND: Vitiligo is a complex disease in which patchy depigmentation is the result of an autoimmune-induced loss of melanocytes in affected regions. On the basis of a genome-wide linkage analysis of vitiligo in the Chinese Han population, we previously showed significant evidence of a linkage between 22q12 and vitiligo. Our aim in the current study was to identify vitiligo susceptibility variants within an expanded region of the 22q12 locus. METHODS AND RESULTS: An in-depth analysis of the expanded region of the 22q12 locus was performed by imputation using a large GWAS dataset consisting of 1117 cases and 1701 controls. Eight nominal SNPs were selected and genotyped in an independent cohort of Chinese Han individuals (2069 patients and 1370 control individuals) by using the Sequenom MassArray iPLEX1 system. The data were analyzed with PLINK 1.07 software. The C allele of rs730669 located in ZDHHC8/RTN4R showed a strong association with vitiligo (P = 3.25 × 10-8, OR = 0.81). The C allele of rs4820338 located in VPREB1 and the A allele of rs2051582 (a SNP reported in our previous study) located in IL2RB showed a suggestive association with vitiligo (P = 1.04 × 10-5, OR = 0.86; P = 1.78 × 10-6, OR = 1.27). The three identified SNPs showed independent associations with vitiligo in a conditional logistic regression analysis (all P < 1.0 × 10-5; all D' < 0.05 and r2 < 1.0 × 10-4). CONCLUSIONS: The study reveals that two novel variants rs730669 (ZDHHC8/RTN4R) and rs4820338 (VPREB1) on 22q11.2 might confer susceptibility to vitiligo and affect disease subphenotypes. The presence of multiple independent variants emphasizes their important roles in the genetic pathogenesis of disease.
Authors: Ying Jin; Stanca A Birlea; Pamela R Fain; Katherine Gowan; Sheri L Riccardi; Paulene J Holland; Christina M Mailloux; Alexandra J D Sufit; Saunie M Hutton; Anita Amadi-Myers; Dorothy C Bennett; Margaret R Wallace; Wayne T McCormack; E Helen Kemp; David J Gawkrodger; Anthony P Weetman; Mauro Picardo; Giovanni Leone; Alain Taïeb; Thomas Jouary; Khaled Ezzedine; Nanny van Geel; Jo Lambert; Andreas Overbeck; Richard A Spritz Journal: N Engl J Med Date: 2010-04-21 Impact factor: 91.245
Authors: Ying Jin; Stanca A Birlea; Pamela R Fain; Christina M Mailloux; Sheri L Riccardi; Katherine Gowan; Paulene J Holland; Dorothy C Bennett; Margaret R Wallace; Wayne T McCormack; E Helen Kemp; David J Gawkrodger; Anthony P Weetman; Mauro Picardo; Giovanni Leone; Alain Taïeb; Thomas Jouary; Khaled Ezzedine; Nanny van Geel; Jo Lambert; Andreas Overbeck; Richard A Spritz Journal: Nat Genet Date: 2010-06-06 Impact factor: 38.330
Authors: K Ezzedine; H W Lim; T Suzuki; I Katayama; I Hamzavi; C C E Lan; B K Goh; T Anbar; C Silva de Castro; A Y Lee; D Parsad; N van Geel; I C Le Poole; N Oiso; L Benzekri; R Spritz; Y Gauthier; S K Hann; M Picardo; A Taieb Journal: Pigment Cell Melanoma Res Date: 2012-05 Impact factor: 4.693
Authors: Ying Jin; Genevieve Andersen; Daniel Yorgov; Tracey M Ferrara; Songtao Ben; Kelly M Brownson; Paulene J Holland; Stanca A Birlea; Janet Siebert; Anke Hartmann; Anne Lienert; Nanja van Geel; Jo Lambert; Rosalie M Luiten; Albert Wolkerstorfer; J P Wietze van der Veen; Dorothy C Bennett; Alain Taïeb; Khaled Ezzedine; E Helen Kemp; David J Gawkrodger; Anthony P Weetman; Sulev Kõks; Ele Prans; Külli Kingo; Maire Karelson; Margaret R Wallace; Wayne T McCormack; Andreas Overbeck; Silvia Moretti; Roberta Colucci; Mauro Picardo; Nanette B Silverberg; Mats Olsson; Yan Valle; Igor Korobko; Markus Böhm; Henry W Lim; Iltefat Hamzavi; Li Zhou; Qing-Sheng Mi; Pamela R Fain; Stephanie A Santorico; Richard A Spritz Journal: Nat Genet Date: 2016-10-10 Impact factor: 38.330
Authors: Ying Jin; Stanca A Birlea; Pamela R Fain; Tracey M Ferrara; Songtao Ben; Sheri L Riccardi; Joanne B Cole; Katherine Gowan; Paulene J Holland; Dorothy C Bennett; Rosalie M Luiten; Albert Wolkerstorfer; J P Wietze van der Veen; Anke Hartmann; Saskia Eichner; Gerold Schuler; Nanja van Geel; Jo Lambert; E Helen Kemp; David J Gawkrodger; Anthony P Weetman; Alain Taïeb; Thomas Jouary; Khaled Ezzedine; Margaret R Wallace; Wayne T McCormack; Mauro Picardo; Giovanni Leone; Andreas Overbeck; Nanette B Silverberg; Richard A Spritz Journal: Nat Genet Date: 2012-05-06 Impact factor: 38.330