Department of Dermatology, Santa Casa de Misericórdia Hospital, Pontifical Catholic University of Paraná, Curitiba, Paraná, Brazil.
J Invest Dermatol. 2010 Jul;130(7):1813-8. doi: 10.1038/jid.2010.34. Epub 2010 Feb 25.
Vitiligo is a chronic disease characterized by macules devoid of melanin and identifiable melanocytes. Adhesion of melanocytes to the basement membrane by integrin CCN3 is mediated through collagen IV receptor DDR1. We hypothesize that genetic variants of the DDR1 gene are associated with the occurrence of vitiligo. To test this hypothesis, we genotyped 10 DDR1 tag single-nucleotide polymorphisms (SNPs) in 212 trios composed of an affected child and both parents. Associated markers were then genotyped in 134 independent, unrelated individuals with vitiligo and 134 unrelated controls. Allele T of tag SNP rs4618569 was associated with an increased risk for vitiligo in the family trios (P=0.002, odds ratio (OR)=5.27; 95% confidence interval (CI)=1.59-17.40), whereas allele C of tag SNP rs2267641 was associated with an increased risk for vitiligo in both family-based and case-control populations (P=0.01, OR=3.47; 95% CI=1.22-9.17; P=0.04, OR=6.00; 95% CI=1.73-52.33, respectively). The best evidence for association in the trios was obtained for a haplotype composed of risk alleles of markers rs4618569 and rs2267641 (P=0.0006). There was an age-dependent enrichment of rs4618569 T allele and rs2267641 C allele in early-onset affected individuals. In conclusion, we propose DDR1 as a susceptibility gene for vitiligo, possibly implicating a defective cell adhesion in vitiligo pathogenesis.
白癜风是一种以黑素细胞缺失和可识别的黑素细胞为特征的慢性疾病。整合素 CCN3 通过胶原蛋白 IV 受体 DDR1 将黑素细胞黏附于基膜。我们假设 DDR1 基因的遗传变异与白癜风的发生有关。为了验证这一假说，我们对由一个患病孩子及其父母组成的 212 个三核苷酸组中的 10 个 DDR1 标签单核苷酸多态性（SNP）进行了基因分型。然后，在 134 名独立的、无关的白癜风患者和 134 名无关的对照者中对关联标记物进行了基因分型。标签 SNP rs4618569 的等位基因 T 与家系三核苷酸组中白癜风的发病风险增加相关（P=0.002，比值比（OR）=5.27；95%置信区间（CI）=1.59-17.40），而标签 SNP rs2267641 的等位基因 C 与家系和病例对照人群中的白癜风发病风险增加相关（P=0.01，OR=3.47；95%CI=1.22-9.17；P=0.04，OR=6.00；95%CI=1.73-52.33）。在三核苷酸组中，与 rs4618569 和 rs2267641 标记物的风险等位基因组成的单倍型相关性最佳（P=0.0006）。rs4618569 T 等位基因和 rs2267641 C 等位基因在早发性发病个体中存在年龄依赖性富集。总之，我们提出 DDR1 是白癜风的易感基因，可能暗示细胞黏附缺陷在白癜风发病机制中起作用。
