美国研究人员借助全基因组扫描发现，基因SFTPA2的某种变异与特发性肺纤维化有关。这是迄今发现的与这种致命遗传性肺病相关的第三种基因。
特发性肺纤维化是一种常见于老年人的致命肺病，患者多在50岁以上发病，在确诊后3年内就可能死亡，目前尚无针对该病的有效治疗方法。在这种疾病中，遗传性病例约占2％，研究人员希望从遗传性患者入手，找到与该病有关的基因变异，最终开发出基因疗法，以战胜这一病魔。
得克萨斯大学西南医学中心的研究人员在新一期《美国人类遗传学杂志》网络版上介绍说，2007年，他们曾以两个有多人患此病的大家族为对象进行基因分析。结果发现，基因TERT和基因TERC的变异会诱发这种肺病。遗传性的特发性肺纤维化患者中，约15％的人会出现这两种基因变异。
在最新研究中，研究人员通过全基因组扫描，对上述两种基因未出现变异的遗传性特发性肺纤维化患者进行了对比分析，结果发现了第三种致病基因SETPA2。该基因正常情况下负责抵御入侵肺部的病原体，但分析发现，假如它发生某种形式的变异，变异者不仅可能出现肺纤维化，还可能患肺癌。
目前，研究人员正在进行相关的细胞分子研究，以确定为何上述3种基因的变异会使人罹患特发性肺纤维化的风险升高。他们还打算进行动物实验，以研究SETPA2基因对肺部不同细胞的影响。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
