Hirano Chihiro, Ohshimo Shinichiro, Horimasu Yasushi, Iwamoto Hiroshi, Fujitaka Kazunori, Hamada Hironobu, Hattori Noboru, Shime Nobuaki, Bonella Francesco, Guzman Josune, Costabel Ulrich, Kohno Nobuoki
Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan.
Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan; Department of Emergency and Critical Care Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan.
Respir Med. 2017 Feb;123:105-109. doi: 10.1016/j.rmed.2016.12.007. Epub 2016 Dec 22.
Family with sequence similarity 13, member A (FAM13A) variants have been associated with susceptibility to chronic lung diseases. A recent genome-wide association study has shown an association between a polymorphism in FAM13A rs2609255 and idiopathic interstitial pneumonias in a Caucasian population. However, the relationship between rs2609255 polymorphism and prognosis in idiopathic interstitial pneumonias has not been investigated.
Sixty-five patients with idiopathic pulmonary fibrosis (IPF) and 310 Japanese healthy volunteers were enrolled in this study. Genomic DNA was extracted from all subjects. rs2609255 was genotyped by a commercially available assay. The correlations between rs2609255 polymorphism and survival and the occurrence of acute exacerbation were evaluated.
The frequency of the minor G allele was significantly higher in IPF patients (59.2%) than in controls (41.9%; OR = 1.78, 95% CI; 1.29-2.44, p < 0.001). The rs2609255 major T allele was associated with lower diffusing capacity of carbon monoxide values and higher composite physiologic index after adjustment for age, sex and smoking (β = -7.20, p = 0.005 and β = 5.59, p = 0.009, respectively). In the Kaplan-Meier analysis, the T allele carriers showed a significantly increased mortality compared to the non-carriers (p < 0.05). In the multivariate Cox-proportional hazards analysis, the T allele of rs2609255 was independently associated with poor survival (hazard ratio, 5.37; p = 0.031; 95% confidence interval, 1.16-24.82).
FAM13A gene polymorphism showed a significant association with the susceptibility to IPF, with severity of lung function impairment and with poor prognosis.
家族序列相似性13成员A（FAM13A）变异与慢性肺部疾病易感性相关。最近一项全基因组关联研究显示，FAM13A基因rs2609255位点的多态性与白种人群特发性间质性肺炎有关。然而，rs2609255多态性与特发性间质性肺炎预后的关系尚未得到研究。
本研究纳入65例特发性肺纤维化（IPF）患者和310名日本健康志愿者。从所有受试者中提取基因组DNA。采用商业检测方法对rs2609255进行基因分型。评估rs2609255多态性与生存率及急性加重发生之间的相关性。
IPF患者中次要G等位基因频率（59.2%）显著高于对照组（41.9%；比值比=1.78，95%可信区间：1.29 - 2.44，p<0.001）。在校正年龄、性别和吸烟因素后，rs2609255主要T等位基因与较低的一氧化碳弥散量值及较高的综合生理指数相关（β=-7.20，p=0.005；β=5.59，p=0.009）。在Kaplan-Meier分析中，T等位基因携带者的死亡率显著高于非携带者（p<0.05）。在多变量Cox比例风险分析中，rs2609255的T等位基因与不良生存独立相关（风险比，5.37；p=0.031；95%可信区间，1.16 - 24.82）。
FAM13A基因多态性与IPF易感性、肺功能损害严重程度及不良预后显著相关。
