Variants of the ABCA3 gene might contribute to susceptibility to interstitial lung diseases in the Chinese population.
Variants of the ABCA3 gene might contribute to susceptibility to interstitial lung diseases in the Chinese population.
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ABCA3基因的变异可能导致中国人群对间质性肺疾病的易感性
DOI：
10.1038/s41598-017-04486-y
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发表时间：
2017-06-22
影响因子：
4.6
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Zhou W;Zhuang Y;Sun J;Wang X;Zhao Q;Xu L;Wang Y
ATP结合盒A3（ABCA 3）是一种磷脂载体，主要表达于肺泡上皮细胞。ABCA 3的双等位基因突变与儿童致命性呼吸窘迫综合征和间质性肺病（ILD）相关。然而，ABCA 3的变异是否在成人ILD（包括特发性肺纤维化（IPF））的发生中起作用仍有待解决。在这项研究中，我们通过外显子测序在30例散发性IPF患者和30例匹配的健康对照中筛选ABCA 3的种系变异体。其中13例患者中发现11种错义突变，以杂合子为主，而2例健康对照中仅发现2种错义突变。然后，我们选择了四种检测到的错义变体（p.L39V、p.S828F、p.V968M和p.G1205R），在1,024例ILD患者（包括250例IPF和774例结缔组织病-ILD（CTD-ILD）患者）和1,054例健康个体中进行队列分析。我们的研究结果表明，p.G1205R的等位基因频率，而不是p.L39V，ILD患者显著高于健康对照组。然而，在队列分析中未检测到携带变体p.S828F或p.V968M的其他受试者。这些结果表明，杂合ABCA 3基因变异可能有助于中国人群的疾病易感性。
ATP-binding cassette A3 (ABCA3) is a phospholipid carrier that is mainly expressed in the alveolar epithelium. Biallelic mutations of ABCA3 has been associated with fatal respiratory distress syndrome and interstitial lung disease (ILD) in children. However, whether variations in ABCA3 have a role in the development of adult ILD, including idiopathic pulmonary fibrosis (IPF), remains to be addressed. In this study, we screened for germline variants of ABCA3 by exons-sequencing in 30 patients with sporadic IPF and in 30 matched healthy controls. Eleven missense variants, predominantly in heterozygous, were found in 13 of these patients, but only two missenses in 2 healthy controls. We then selected four of the detected missense variants (p.L39V, p.S828F, p.V968M and p.G1205R) to performed cohort analysis in 1,024 ILD patients, containing 250 IPF and 774 connective tissue disease-ILD (CTD-ILD) patients, and 1,054 healthy individuals. Our results showed that the allele frequency of p.G1205R, but not p.L39V, was significantly higher in ILD patients than in healthy controls. However, no additional subject carrying the variant p.S828F or p.V968M was detected in the cohort analysis. These results indicate that the heterozygous ABCA3 gene variants may contribute to susceptibility to diseases in the Chinese population.