Wang Han, Wang Yuxuan, Tang Yundi, Ye Hua, Zhang Xuewu, Zhou Gengmin, Lv Jiyang, Cai Yongjiang, Li Zhanguo, Guo Jianping, Wang Qingwen
Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen, China.
Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
Front Genet. 2019 Sep 18;10:869. doi: 10.3389/fgene.2019.00869. eCollection 2019.
Leukocyte immunoglobulin-like receptor A3 () belongs to the LILR family with unique feature of a 6.7-kb deletion variation among individuals. Frequencies of the 6.7-kb deletion vary widely across populations, but so far it has not been carefully investigated among Han Chinese subpopulations. Furthermore, we previously identified the non-deleted (functional) as a novel genetic risk for multiple autoimmune diseases. The current study aimed to investigate (i) whether frequencies of the 6.7-kb deletion differ within Han Chinese subpopulations and (ii) whether the functional is a novel genetic risk for ankylosing spondylitis (AS). The 6.7-kb deletion was genotyped in two independent cohorts, including 1,567 subjects from Shenzhen Hospital and 2,507 subjects from People's Hospital of Peking University. Frequencies of the 6.7-kb deletion were first investigated in combined healthy cohort according to the Chinese administrative district divisions. Association analyses were performed on whole dataset and subsets according to the geographic regions. Impact of the functional on AS disease activity was evaluated. Frequencies of 6.7-kb deletion were highly differentiated within Han Chinese subpopulations, being gradually decreased from Northeast (80.6%) to South (47.4%). Functional seemed to be a strong genetic risk in susceptibility to AS under almost all the alternative genetic models, if the study subjects were not geographically stratified. However, stratification analysis revealed that the functional was consistently associated with AS susceptibility mainly in Northern Han subgroup under the alternative genetic models, but not in Central and Southern Hans. Functional conferred an increased disease activity in AS patients ( < 0.0001 both for CRP and ESR, and = 0.003 for BASDAI). The present study is the first to report that the frequencies of 6.7-kb deletion vary among Chinese Hans across geographic regions. The functional is associated with AS susceptibility mainly in Northern Han, but not in Central and Southern Han subgroups. Our finding provides new evidence that is a common genetic risk for multiple autoimmune diseases and highlights the genetic differentiation among different ethnicities, even within the subpopulations of an ethnic group.
白细胞免疫球蛋白样受体A3（）属于LILR家族，个体间具有独特的6.7 kb缺失变异特征。6.7 kb缺失的频率在不同人群中差异很大，但迄今为止，尚未在汉族亚人群中进行仔细研究。此外，我们之前已确定非缺失型（功能性）是多种自身免疫性疾病的一种新的遗传风险因素。本研究旨在调查：（i）汉族亚人群中6.7 kb缺失的频率是否存在差异；（ii）功能性是否是强直性脊柱炎（AS）的一种新的遗传风险因素。在两个独立队列中对6.7 kb缺失进行基因分型，包括来自深圳医院的1567名受试者和北京大学人民医院的2507名受试者。首先根据中国行政区划分，在合并的健康队列中调查6.7 kb缺失的频率。根据地理区域对整个数据集和子集进行关联分析。评估功能性对AS疾病活动度的影响。汉族亚人群中6.7 kb缺失的频率高度分化，从东北（80.6%）到南方（47.4%）逐渐降低。如果研究对象未按地理分层，在几乎所有替代遗传模型下，功能性似乎是AS易感性的一个强大遗传风险因素。然而，分层分析显示，在替代遗传模型下，功能性主要在北方汉族亚组中始终与AS易感性相关，而在中部和南方汉族中则不然。功能性使AS患者的疾病活动度增加（CRP和ESR均P<0.0001，BASDAI的P = 0.003）。本研究首次报告6.7 kb缺失的频率在中国不同地理区域的汉族人群中存在差异。功能性主要与北方汉族的AS易感性相关，而与中部和南方汉族亚组无关。我们的发现提供了新的证据，表明是多种自身免疫性疾病的常见遗传风险因素，并突出了不同种族之间的遗传分化，即使在一个种族的亚人群中也是如此。
