Association between MUC5B and TERT polymorphisms and different interstitial lung disease phenotypes.
Association between MUC5B and TERT polymorphisms and different interstitial lung disease phenotypes.
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DOI：
10.1016/j.trsl.2013.12.006
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Liu W
中科院分区：
文献类型：
--
作者：
Wei R;Li C;Zhang M;Jones-Hall YL;Myers JL;Noth I;Liu W
在最近的全基因组遗传学研究中，TERT和MUC 5 B多态性一直与特发性肺纤维化（IPF）相关。然而，目前尚不清楚这两个基因座如何有助于对散发性间质性肺病（ILD）的不同实体的易感性。我们试图在高加索人群中检测这两种多态性与IPF和非IPF ILD实体的相关性。使用227名ILD患者和689名对照检测了TERT（rs 2736100）和MUC 5 B（rs35705950）两种多态性与IPF或非IPF散发性ILD之间的关联。基因型数据也与ILD患者的肺功能测定相关。因此，rs 2736100和rs35705950作为单一表型与ILD显著且独立相关[比值比（OR）=1.29，95%置信区间（CI）：1.04-1.60，p= 2×10−2和OR=2.22，95%CI：1.69-2.92，p=7×10−9]。当单独考虑IPF和“其他ILD”（非IPF）时，rs35705950与IPF（OR=3.2，95%CI：2.21-4.63，p=1.2×10−10）的相关性强于其他ILD（OR=1.72，95%CI：1.22-2.42，p=1.2×10−3）。相比之下，rs 2736100与其他ILD相关（OR=1.43，95%CI：1.11-1.85，p=6.2×10−3），但与IPF无关（OR=1.08，95%CI：0.78-1.49，p>0.05）。RS35705950与肺功能增加显著相关（p<0.05）。在IPF和其他ILD组中，它也与无气流阻塞的ILD相关（两组均为p<0.01），并赋予无气流阻塞的IPF最高风险（OR=4.46，95%CI：2.60-7.66，p=4.5×10−9）。我们的研究表明，虽然这两个基因座赋予ILD独立的风险，rs35705950可能特别有助于差异性IPF和其他ILD实体。我们的研究进一步强调了ILD的遗传和表型异质性。
TERT and MUC5B polymorphisms have been consistently associated with idiopathic pulmonary fibrosis (IPF) in recent genome-wide genetic studies. However, it remains unclear how both loci contribute to the susceptibility to different entities of sporadic interstitial lung disease (ILD). We sought to test the associations of the two polymorphisms with IPF and non-IPF ILD entities in a Caucasian population. Associations between two polymorphisms in TERT (rs2736100) and MUC5B (rs35705950) and IPF or non-IPF sporadic ILD were tested using 227 ILD patients and 689 controls. Genotypic data were also correlated with pulmonary functions measured in ILD patients. As a result, rs2736100 and rs35705950 were significantly and independently associated with ILD as a single phenotype [Odds ratio (OR)=1.29, 95% Confidence Interval (CI): 1.04–1.60, p= 2×10−2 and OR=2.22, 95%CI: 1.69–2.92, p=7×10−9, respectively). When considering IPF and “other ILD” (non-IPF) separately, rs35705950 had a stronger association with IPF (OR=3.2, 95%CI: 2.21–4.63, p=1.2×10−10) than other ILD (OR=1.72, 95%CI: 1.22–2.42, p=1.2×10−3). In contrast, rs2736100 was associated with other ILD (OR=1.43, 95%CI: 1.11–1.85, p=6.2×10−3) but not IPF (OR=1.08, 95%CI: 0.78–1.49, p>0.05). Rs35705950 was significantly correlated with increased pulmonary function (p<0.05). It was also associated with ILD without airflow obstruction in both IPF and other ILD groups (p<0.01 for both), and conferred the highest risk for IPF without airflow obstruction (OR=4.46, 95%CI: 2.60–7.66, p=4.5×10−9). Our study suggests that while both loci confer independent risks for ILD, rs35705950 may particularly contribute differentially to IPF and other ILD entities. Our study further highlighted the genetic and phenotypic heterogeneity of ILD.
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影响因子：
30.8
作者：
Fingerlin, Tasha E.;Murphy, Elissa;Zhang, Weiming;Peljto, Anna L.;Brown, Kevin K.;Steele, Mark P.;Loyd, James E.;Cosgrove, Gregory P.;Lynch, David;Groshong, Steve;Collard, Harold R.;Wolters, Paul J.;Bradford, Williamson Z.;Kossen, Karl;Seiwert, Scott D.;du Bois, Roland M.;Garcia, Christine Kim;Devine, Megan S.;Gudmundsson, Gunnar;Isaksson, Helgi J.;Kaminski, Naftali;Zhang, Yingze;Gibson, Kevin F.;Lancaster, Lisa H.;Cogan, Joy D.;Mason, Wendi R.;Maher, Toby M.;Molyneaux, Philip L.;Wells, Athol U.;Moffatt, Miriam F.;Selman, Moises;Pardo, Annie;Kim, Dong Soon;Crapo, James D.;Make, Barry J.;Regan, Elizabeth A.;Walek, Dinesha S.;Daniel, Jerry J.;Kamatani, Yoichiro;Zelenika, Diana;Smith, Keith;McKean, David;Pedersen, Brent S.;Talbert, Janet;Kidd, Raven N.;Markin, Cheryl R.;Beckman, Kenneth B.;Lathrop, Mark;Schwarz, Marvin I.;Schwartz, David A.
通讯作者：
Schwartz, David A.
DOI：
10.1056/nejmoa1216076
发表时间：
2013-06-06
期刊：
The New England journal of medicine
影响因子：
--
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
通讯作者：
Schwartz DA
DOI：
10.1513/pats.201008-056ms
发表时间：
2011-05-01
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
Garcia, Christine Kim
通讯作者：
Garcia, Christine Kim
DOI：
10.1097/maj.0b013e31821a9d8e
发表时间：
2011-06
期刊：
The American journal of the medical sciences
影响因子：
--
作者：
Zoz DF;Lawson WE;Blackwell TS
通讯作者：
Blackwell TS
影响因子：
76.2
作者：
Noth, Imre;Zhang, Yingze;Ma, Shwu-Fan;Flores, Carlos;Barber, Mathew;Huang, Yong;Broderick, Steven M.;Wade, Michael S.;Hysi, Pirro;Scuirba, Joseph;Richards, Thomas J.;Juan-Guardela, Brenda M.;Vij, Rekha;Han, MeiLan K.;Martinez, Fernando J.;Kossen, Karl;Seiwert, Scott D.;Christie, Jason D.;Nicolae, Dan;Kaminski, Naftali;Garcia, Joe G. N.
通讯作者：
Garcia, Joe G. N.