Zhou Xiaodong, Lee Jong Eun, Arnett Frank C, Xiong Momiao, Park Min Young, Yoo Yeon Kyeong, Shin Eun Soon, Reveille John D, Mayes Maureen D, Kim Jin Hyun, Song Ran, Choi Ji Yong, Park Ji Ah, Lee Yun Jong, Lee Eun Young, Song Yeong Wook, Lee Eun Bong
University of Texas Health Science Center at Houston, Houston, TX, USA.
Arthritis Rheum. 2009 Dec;60(12):3807-14. doi: 10.1002/art.24982.
To identify systemic sclerosis (SSc) susceptibility loci via a genome-wide association study.
A genome-wide association study was performed in 137 patients with SSc and 564 controls from Korea using the Affymetrix Human SNP Array 5.0. After fine-mapping studies, the results were replicated in 1,107 SSc patients and 2,747 controls from a US Caucasian population.
The single-nucleotide polymorphisms (SNPs) (rs3128930, rs7763822, rs7764491, rs3117230, and rs3128965) of HLA-DPB1 and DPB2 on chromosome 6 formed a distinctive peak with log P values for association with SSc susceptibility (P=8.16x10(-13)). Subtyping analysis of HLA-DPB1 showed that DPB11301 (P=7.61x10(-8)) and DPB10901 (P=2.55x10(-5)) were the subtypes most susceptible to SSc in Korean subjects. In US Caucasians, 2 pairs of SNPs, rs7763822/rs7764491 and rs3117230/rs3128965, showed strong association with SSc patients who had either circulating anti-DNA topoisomerase I (P=7.58x10(-17)/4.84x10(-16)) or anticentromere autoantibodies (P=1.12x10(-3)/3.2x10(-5)), respectively.
The results of our genome-wide association study in Korean subjects indicate that the region of HLA-DPB1 and DPB2 contains the loci most susceptible to SSc in a Korean population. The confirmatory studies in US Caucasians indicate that specific SNPs of HLA-DPB1 and/or DPB2 are strongly associated with US Caucasian patients with SSc who are positive for anti-DNA topoisomerase I or anticentromere autoantibodies.
通过全基因组关联研究确定系统性硬化症（SSc）的易感基因座。
使用Affymetrix人类SNP Array 5.0对137例韩国SSc患者和564例对照进行全基因组关联研究。经过精细定位研究后，在美国白种人的1107例SSc患者和2747例对照中对结果进行重复验证。
6号染色体上HLA-DPB1和DPB2的单核苷酸多态性（SNP）（rs3128930、rs7763822、rs7764491、rs3117230和rs3128965）形成了一个独特的峰值，与SSc易感性相关的对数P值（P = 8.16×10⁻¹³）。HLA-DPB1的亚型分析表明，DPB11301（P = 7.61×10⁻⁸）和DPB10901（P = 2.55×10⁻⁵）是韩国受试者中最易患SSc的亚型。在美国白种人中，两对SNP，即rs7763822/rs7764491和rs3117230/rs3128965，分别与循环抗DNA拓扑异构酶I（P = 7.58×10⁻¹⁷/4.84×10⁻¹⁶）或抗着丝粒自身抗体（P = 1.12×10⁻³/3.2×10⁻⁵）阳性的SSc患者有很强的相关性。
我们在韩国受试者中进行的全基因组关联研究结果表明，HLA-DPB1和DPB2区域包含韩国人群中最易患SSc的基因座。在美国白种人中进行的验证性研究表明，HLA-DPB1和/或DPB2的特定SNP与抗DNA拓扑异构酶I或抗着丝粒自身抗体阳性的美国白种人SSc患者密切相关。
