Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis
Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis
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DOI：
10.1136/thoraxjnl-2012-201786
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发表时间：
2013-05-01
期刊：
影响因子：
10
通讯作者：
Renzoni, Elisabetta A.
中科院分区：
文献类型：
--
作者：
Stock, Carmel J.;Sato, Hiroe;Renzoni, Elisabetta A.
背景 MUC5B（编码粘蛋白 5 亚型 B 的基因）上游 3 kb 的多态性 (rs35705950) 已被证明与家族性和散发性特发性肺纤维化 (IPF) 相关。我们着手验证该变异是否也是其他环境下纤维化肺病的危险因素，并确认在英国白种人 IPF 人群中发表的研究结果。方法对英国白种人健康对照 (n=416) 和患有 IPF (n=110)、结节病 (n=180) 和系统性硬化症 (SSc) (n=440) 的患者进行基因分型，以测试关联性。 SSc 和结节病队列根据是否存在纤维化肺病进行细分。为了评估与疾病进展的相关性，在 IPF 和 SSc 组中使用了用力肺活量和/或肺一氧化碳转移因子下降的时间，而在结节病患者中评估了自基线起 4 年的持续下降。 结果 MUC5B 启动子单核苷酸多态性与 IPF 显着相关（p=2.04x10(-17)；OR 4.90，95% CI 3.42 至 7.03）在英国人群中得到证实。 MUC5B 变异不是 SSc 或结节病患者肺纤维化的危险因素，并且不能预测任何组中进展更快的肺部疾病。相反，在 IPF 患者中观察到用力肺活量有较长时间下降的趋势。结论我们证实了 MUC5B 变异与 IPF 的关联。我们没有观察到 SSc 或结节病与肺纤维化之间的关联，这可能凸显了遗传易感性的根本差异，尽管有限的亚组数量不允许明确排除关联。
Background A polymorphism (rs35705950) 3 kb upstream of MUC5B, the gene encoding Mucin 5 subtype B, has been shown to be associated with familial and sporadic idiopathic pulmonary fibrosis (IPF). We set out to verify whether this variant is also a risk factor for fibrotic lung disease in other settings and to confirm the published findings in a UK Caucasian IPF population.Methods Caucasian UK healthy controls (n=416) and patients with IPF (n=110), sarcoidosis (n=180) and systemic sclerosis (SSc) (n=440) were genotyped to test for association. The SSc and sarcoidosis cohorts were subdivided according to the presence or absence of fibrotic lung disease. To assess correlation with disease progression, time to decline in forced vital capacity and/or lung carbon monoxide transfer factor was used in the IPF and SSc groups, while a persistent decline at 4 years since baseline was evaluated in patients with sarcoidosis.Results A significant association of the MUC5B promoter single nucleotide polymorphism with IPF (p=2.04x10(-17); OR 4.90, 95% CI 3.42 to 7.03) was confirmed in this UK population. The MUC5B variant was not a risk factor for lung fibrosis in patients with SSc or sarcoidosis and did not predict more rapidly progressive lung disease in any of the groups. Rather, a trend for a longer time to decline in forced vital capacity was observed in patients with IPF.Conclusions We confirm the MUC5B variant association with IPF. We did not observe an association with lung fibrosis in the context of SSc or sarcoidosis, potentially highlighting fundamental differences in genetic susceptibility, although the limited subgroup numbers do not allow a definitive exclusion of an association.