亚洲皮肤科学会主席、安徽医科大学校长张学军教授（资料图）
安徽医科大学张学军教授团队和香港大学刘宇隆教授团队合作，又发现了5个红斑狼疮易感基因。相关研究论文近日在线发表在《美国人类遗传学杂志》上。
据悉，这是亚洲地区第一项系统性红斑狼疮全基因组关联Meta分析的研究成果。Meta分析又称荟萃分析，是指用统计学方法对搜集的多个研究资料进行分析和概括，可增强结论的可信度。
2009年，张学军研究团队曾发现5个与汉族人群红斑狼疮发病密切相关的易感基因ETS1、IKZF1、RASGRP3、SLC15A4和TNIP1。此次，内地和香港学者利用两个团队各自拥有的红斑狼疮全基因组关联分析数据进行Meta分析，并在我国大陆、香港地区、台湾地区、泰国曼谷4个亚洲汉族人群中进行大样本验证，又发现了5个与系统性红斑狼疮相关的易感基因CDKN1B、TET3、CD80、DRAM1和ARID5B，并揭示细胞周期调节、吞噬及DNA甲基化等机制在红斑狼疮发病中具有重要作用。
该研究不仅发现了红斑狼疮发病机制中的遗传危险因素在不同人种间具有遗传异质性，而且揭示了疾病新的发病通路，为揭示疾病病因和发病机制研究提供了新的科学依据。
Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians
Wanling Yang, Huayang Tang, Yan Zhang, Xianfa Tang, Jing Zhang, Liangdan Sun, Jing Yang, Yong Cui, Lu Zhang, Nattiya Hirankarn, Hui Cheng, Hai-Feng Pan, Jinping Gao, Tsz Leung Lee, Yujun Sheng, Chak Sing Lau, Yang Li, Tak Mao Chan, Xianyong Yin, Dingge Ying, Qianjin Lu, Alexander Moon Ho Leung, Xianbo Zuo, Xiang Chen, Kwok Lung Tong, Fusheng Zhou, Qingchun Diao, Niko Kei Chiu Tse, Hongfu Xie, Chi Chiu Mok, Fei Hao, Sik Nin Wong, Bingjun Shi, Ka Wing Lee, Yan Hui, Marco Hok Kung Ho, Bo Liang, Pamela Pui Wah Lee, Hongzhou Cui, Qing Guo, Brian Hon-Yin Chung, Xiongming Pu, Qiji Liu, Xiaoguang Zhang, Change Zhang, Chun Yin Chong, Hong Fang, Raymond Woon Sing Wong, Yonghu Sun, Mo Yin Mok, Xiang-Pei Li, Yingyos Avihingsanon, Zhifang Zhai, Pornpimol Rianthavorn, Thavatchai Deekajorndej, Kanya Suphapeetiporn, Fei Gao, Vorasuk Shotelersuk, Xiaojing Kang, Shirley King Yee Ying, Lijuan Zhang, Wilfred Hing Sang Wong, Dingxian Zhu, Samuel Ka Shun Fung, Fanqin Zeng, Wai Ming Lai, Chun-Ming Wong, Irene Oi Lin Ng, Maria-Mercè Garcia-Barceló, Stacey S. Cherny, Nan Shen, Paul Kwong-Hang Tam, Pak Chung Sham, Dong-Qing Ye, Sen Yang, Xuejun Zhang, and Yu Lung Lau
Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases.
