安徽醫(yī)科大學(xué)張學(xué)軍教授團(tuán)隊(duì)和香港大學(xué)劉宇隆教授團(tuán)隊(duì)合作,，又發(fā)現(xiàn)了5個(gè)紅斑狼瘡易感基因。相關(guān)研究論文近日在線發(fā)表在《美國人類遺傳學(xué)雜志》上,。
據(jù)悉,，這是亞洲地區(qū)第一項(xiàng)系統(tǒng)性紅斑狼瘡全基因組關(guān)聯(lián)Meta分析的研究成果。Meta分析又稱薈萃分析,，是指用統(tǒng)計(jì)學(xué)方法對(duì)搜集的多個(gè)研究資料進(jìn)行分析和概括,，可增強(qiáng)結(jié)論的可信度。
2009年,，張學(xué)軍研究團(tuán)隊(duì)曾發(fā)現(xiàn)5個(gè)與漢族人群紅斑狼瘡發(fā)病密切相關(guān)的易感基因ETS1,、IKZF1、RASGRP3,、SLC15A4和TNIP1,。此次，內(nèi)地和香港學(xué)者利用兩個(gè)團(tuán)隊(duì)各自擁有的紅斑狼瘡全基因組關(guān)聯(lián)分析數(shù)據(jù)進(jìn)行Meta分析,，并在我國大陸,、香港地區(qū)、臺(tái)灣地區(qū),、泰國曼谷4個(gè)亞洲漢族人群中進(jìn)行大樣本驗(yàn)證,，又發(fā)現(xiàn)了5個(gè)與系統(tǒng)性紅斑狼瘡相關(guān)的易感基因CDKN1B、TET3,、CD80,、DRAM1和ARID5B，并揭示細(xì)胞周期調(diào)節(jié),、吞噬及DNA甲基化等機(jī)制在紅斑狼瘡發(fā)病中具有重要作用,。
該研究不僅發(fā)現(xiàn)了紅斑狼瘡發(fā)病機(jī)制中的遺傳危險(xiǎn)因素在不同人種間具有遺傳異質(zhì)性，而且揭示了疾病新的發(fā)病通路,，為揭示疾病病因和發(fā)病機(jī)制研究提供了新的科學(xué)依據(jù),。(生物谷Bioon.com)
doi: 10.1016/j.ajhg.2012.11.018
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Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians.
Yang W, Tang H, Zhang Y, Tang X, Zhang J, Sun L, Yang J, Cui Y, Zhang L, Hirankarn N, Cheng H, Pan HF, Gao J, Lee TL, Sheng Y, Lau CS, Li Y, Chan TM, Yin X, Ying D, Lu Q, Leung AM, Zuo X, Chen X, Tong KL, Zhou F, Diao Q, Tse NK, Xie H, Mok CC, Hao F, Wong SN, Shi B, Lee KW, Hui Y, Ho MH, Liang B, Lee PP,Cui H, Guo Q, Chung BH, Pu X, Liu Q, Zhang X, Zhang C, Chong CY, Fang H, Wong RW, Sun Y, Mok MY, Li XP, Avihingsanon Y, Zhai Z, Rianthavorn P,Deekajorndej T, Suphapeetiporn K, Gao F, Shotelersuk V, Kang X, Ying SK, Zhang L, Wong WH, Zhu D, Fung SK, Zeng F, Lai WM, Wong CM, Ng IO, Garcia-Barceló MM, Cherny SS, Shen N, Tam PK, Sham PC, Ye DQ, Yang S, Zhang X, Lau YL.
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.
