MUC5B promoter polymorphism and interstitial lung abnormalities.
MUC5B promoter polymorphism and interstitial lung abnormalities.
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DOI：
10.1056/nejmoa1216076
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发表时间：
2013-06-06
期刊：
影响因子：
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通讯作者：
Schwartz DA
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作者：
Hunninghake GM;Hatabu H;Okajima Y;Gao W;Dupuis J;Latourelle JC;Nishino M;Araki T;Zazueta OE;Kurugol S;Ross JC;San José Estépar R;Murphy E;Steele MP;Loyd JE;Schwarz MI;Fingerlin TE;Rosas IO;Washko GR;O'Connor GT;Schwartz DA
编码粘蛋白5 B的基因MUC 5 B中常见的启动子多态性（rs35705950）与特发性肺纤维化相关。目前尚不清楚这种多态性是否与一般人群中的间质性肺病有关。我们对2633名参与心脏研究的受试者通过胸部容积计算机断层扫描（CT）检测到的间质性肺异常进行了盲法评估。我们评估了rs35705950位点的异常和基因型之间的关系。在评价的2633例胸部CT扫描中，177例（7%）存在间质性肺异常。与无此类异常的受试者相比，有此类异常的受试者更可能出现呼吸急促和慢性咳嗽，以及总肺容量和弥散容量的测量值降低。在调整协变量后，对于每个次要rs35705950等位基因拷贝，间质性肺异常的几率增加2.8倍（95%置信区间[CI]，2.0 - 3.9; P<0.001），明确的肺纤维化CT证据的几率增加6.3倍（95% CI，3.1 - 12.7; P<0.001）。尽管在年龄大于50岁的参与者中，MUC 5 B基因型与间质性肺异常之间存在关联的证据更大，但吸烟史似乎并不影响这种关联。MUC 5 B启动子多态性被发现与一般人群中的间质性肺病相关。虽然这种关联在老年人中更为明显，但似乎不受吸烟的影响。（由美国国立卫生研究院和其他机构资助; ClinicalTrials.gov编号，NCT 00005121。）
A common promoter polymorphism (rs35705950) in MUC5B, the gene encoding mucin 5B, is associated with idiopathic pulmonary fibrosis. It is not known whether this polymorphism is associated with interstitial lung disease in the general population. We performed a blinded assessment of interstitial lung abnormalities detected in 2633 participants in the Framingham Heart Study by means of volumetric chest computed tomography (CT). We evaluated the relationship between the abnormalities and the genotype at the rs35705950 locus. Of the 2633 chest CT scans that were evaluated, interstitial lung abnormalities were present in 177 (7%). Participants with such abnormalities were more likely to have shortness of breath and chronic cough and reduced measures of total lung and diffusion capacity, as compared with participants without such abnormalities. After adjustment for covariates, for each copy of the minor rs35705950 allele, the odds of interstitial lung abnormalities were 2.8 times greater (95% confidence interval [CI], 2.0 to 3.9; P<0.001), and the odds of definite CT evidence of pulmonary fibrosis were 6.3 times greater (95% CI, 3.1 to 12.7; P<0.001). Although the evidence of an association between the MUC5B genotype and interstitial lung abnormalities was greater among participants who were older than 50 years of age, a history of cigarette smoking did not appear to influence the association. The MUC5B promoter polymorphism was found to be associated with interstitial lung disease in the general population. Although this association was more apparent in older persons, it did not appear to be influenced by cigarette smoking. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00005121.)