美國(guó)研究人員借助全基因組掃描發(fā)現(xiàn),，基因SFTPA2的某種變異與特發(fā)性肺纖維化有關(guān)。這是迄今發(fā)現(xiàn)的與這種致命遺傳性肺病相關(guān)的第三種基因,。
特發(fā)性肺纖維化是一種常見于老年人的致命肺病，患者多在50歲以上發(fā)病,，在確診后3年內(nèi)就可能死亡,，目前尚無(wú)針對(duì)該病的有效治療方法。在這種疾病中,，遺傳性病例約占2％,，研究人員希望從遺傳性患者入手，找到與該病有關(guān)的基因變異,，最終開發(fā)出基因療法,，以戰(zhàn)勝這一病魔。
得克薩斯大學(xué)西南醫(yī)學(xué)中心的研究人員在新一期《美國(guó)人類遺傳學(xué)雜志》網(wǎng)絡(luò)版上介紹說(shuō),，2007年,，他們?cè)詢蓚€(gè)有多人患此病的大家族為對(duì)象進(jìn)行基因分析,。結(jié)果發(fā)現(xiàn)，基因TERT和基因TERC的變異會(huì)誘發(fā)這種肺病,。遺傳性的特發(fā)性肺纖維化患者中,，約15％的人會(huì)出現(xiàn)這兩種基因變異。
在最新研究中,，研究人員通過(guò)全基因組掃描,，對(duì)上述兩種基因未出現(xiàn)變異的遺傳性特發(fā)性肺纖維化患者進(jìn)行了對(duì)比分析，結(jié)果發(fā)現(xiàn)了第三種致病基因SETPA2,。該基因正常情況下負(fù)責(zé)抵御入侵肺部的病原體,，但分析發(fā)現(xiàn)，假如它發(fā)生某種形式的變異,，變異者不僅可能出現(xiàn)肺纖維化,，還可能患肺癌。
目前,，研究人員正在進(jìn)行相關(guān)的細(xì)胞分子研究,，以確定為何上述3種基因的變異會(huì)使人罹患特發(fā)性肺纖維化的風(fēng)險(xiǎn)升高,。他們還打算進(jìn)行動(dòng)物實(shí)驗(yàn),，以研究SETPA2基因?qū)Ψ尾坎煌?xì)胞的影響。（生物谷Bioon.com）
生物谷推薦原始出處：
The American Journal of Human Genetics, 18 December 2008 doi:10.1016/j.ajhg.2008.11.010
Genetic Defects in Surfactant Protein A2 Are Associated with Pulmonary Fibrosis and Lung Cancer
Yongyu Wang1,Phillip J. Kuan1,2,Chao Xing1,Jennifer T. Cronkhite1,Fernando Torres2,Randall L. Rosenblatt2,J. Michael DiMaio3,Lisa N. Kinch4,Nick V. Grishin4,5andChristine Kim Garcia1,2,,
1 Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
2 Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
3 Department of Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
4 Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
5 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Idiopathic pulmonary fibrosis (IPF) is a lethal scarring lung disease that affects older adults. Heterozygous rare mutations in the genes encoding telomerase are found in 15% of familial cases. We have used linkage to map another disease-causing gene in a large family with IPF and adenocarcinoma of the lung to a 15.7 Mb region on chromosome 10. We identified a rare missense mutation in a candidate gene, SFTPA2, within the interval encoding surfactant protein A2 (SP-A2). Another rare mutation in SFTPA2 was identified in another family with IPF and lung cancer. Both mutations involve invariant residues in the highly conserved carbohydrate-recognition domain of the protein and are predicted to disrupt protein structure. Recombinant proteins carrying these mutations are retained in the endoplasmic reticulum and are not secreted. These data are consistent with SFTPA2 germline mutations that interfere with protein trafficking and cause familial IPF and lung cancer.
