生物谷綜合：乳糜瀉是一種自體免疫性疾病,，患者對小麥,、黑麥和大麥中的麩質(zhì)蛋白質(zhì)不耐受，引起小腸黏膜病變,，因此也是一種原發(fā)性吸收不良綜合征,。該病在西方人群發(fā)病率約0.03%。
如今,，研究人員在6月在線出版的《自然—遺傳學》（Nature Genetics）上報告說,，在4號染色體上含有4個與遺傳關聯(lián)性密切的基因的區(qū)域隱藏著一些變異，能夠阻止乳糜瀉癥的發(fā)展,。
通過對英國兩組乳糜瀉患者和非患者進行的研究,，David van Heel和同事對乳糜瀉癥進行了全方位的遺傳相關性分析。他們在含有IL2、IL21,、TENR和KIAA1109基因的區(qū)域中鑒別出一種保護型的變異,。KIAA1109是一種功能尚不確定的預測基因。這種相關性反復出現(xiàn)在荷蘭和愛爾蘭人群中,?；騃L2和IL21被認為是解釋這種相關性的最可能基因，因為它們編碼白細胞介素—2和白細胞介素—21的基因,，而這兩種白細胞介素與其他的腸道炎癥有關,。
要確定出這種變異如何防止乳糜瀉癥發(fā)生的機制，還需要繪制出這一區(qū)域的詳細基因圖譜,。（援引科學時報）
原始出處:
Nature Genetics
Published online: 10 June 2007 | doi:10.1038/ng2058
A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21
David A van Heel1, Lude Franke2,17, Karen A Hunt1,17, Rhian Gwilliam3,17, Alexandra Zhernakova2, Mike Inouye3, Martin C Wapenaar4, Martin C N M Barnardo5, Graeme Bethel3, Geoffrey K T Holmes6, Con Feighery7, Derek Jewell8, Dermot Kelleher7, Parveen Kumar1, Simon Travis9, Julian RF Walters10, David S Sanders11, Peter Howdle12, Jill Swift13, Raymond J Playford1, William M McLaren3, M Luisa Mearin14,15, Chris J Mulder16, Ross McManus7, Ralph McGinnis3, Lon R Cardon8, Panos Deloukas3 & Cisca Wijmenga2,4
Abstract
We tested 310,605 SNPs for association in 778 individuals with celiac disease and 1,422 controls. Outside the HLA region, the most significant finding (rs13119723; P = 2.0 10-7) was in the KIAA1109-TENR-IL2-IL21 linkage disequilibrium block. We independently confirmed association in two further collections (strongest association at rs6822844, 24 kb 5' of IL21; meta-analysis P = 1.3 10-14, odds ratio = 0.63), suggesting that genetic variation in this region predisposes to celiac disease.
Centre for Gastroenterology, Institute of Cell and Molecular Science, Queen Mary University of London, London E1 2AT, UK.
Complex Genetics Section, Department of Biomedical Genetics, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Genetics Department, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
Transplant Immunology, Oxford Transplant Centre, Churchill Hospital, Oxford OX3 7LJ, UK.
Department of Gastroenterology, Derbyshire Royal Infirmary, London Road, Derby DE1 2QY, UK.
Departments of Clinical Medicine and Immunology, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Gastroenterology Unit, University of Oxford, Oxford OX3 7BN, UK.
Gastroenterology Section, Imperial College London, Hammersmith Hospital, London W12 0HS, UK.
Department of Gastroenterology and Liver Unit, Royal Hallamshire Hospital, Sheffield S10 2JF, UK.
Department of Gastroenterology, St. James's University Hospital, Leeds LS9 7TF, UK.
Department of Gastroenterology, Llandough Hospital, Penarth CF64 2XX, UK.
Department of Paediatric Gastroenterology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Department of Pediatric Gastroenterology, Vrije University Medical Center, 1007 MB Amsterdam, The Netherlands.
Department of Gastroenterology, Vrije University Medical Center, 1007 MB Amsterdam, The Netherlands.
These authors contributed equally to this work.
Correspondence to: David A van Heel1 e-mail: [email protected]
