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Functional polymorphisms in NFκB1/IκBα predict risks of chronic obstructive pulmonary disease and lung cancer in Chinese.
MedLine Citation:
PMID:  23322360     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Lung inflammation is the major pathogenetic feature for both chronic obstructive pulmonary disease (COPD) and lung cancer. The nuclear factor-kappa B (NFκB) and its inhibitor (IκB) play crucial roles in inflammatory. Here, we tested the hypothesis that single nucleotide polymorphisms (SNPs) in NFκB/IκB confer consistent risks for COPD and lung cancer. Four putative functional SNPs (NFκB1: -94del>insATTG; NFκB2: -2966G>A; IκBα: -826C>T, 2758G>A) were analyzed in southern and validated in eastern Chineses to test their associations with COPD risk in 1,511 COPD patients and 1,677 normal lung function controls, as well as lung cancer risk in 1,559 lung cancer cases and 1,679 cancer-free controls. We found that the -94ins ATTG variants (ins/del + ins/ins) in NFκB1 conferred an increased risk of COPD (OR 1.27, 95 % CI 1.06-1.52) and promoted COPD progression by accelerating annual FEV1 decline (P = 0.015). The 2758AA variant in IκBα had an increased risk of lung cancer (OR 1.53, 95 % CI 1.30-1.80) by decreasing IκBα expression due to the modulation of microRNA hsa-miR-449a but not hsa-miR-34b. Furthermore, both adverse genotypes exerted effect on increasing lung cancer risk in individuals with pre-existing COPD, while the -94del>insATTG did not in those without pre-existing COPD. However, no significant association with COPD or lung cancer was observed for -2966G>A and -826C>T. Our data suggested a common susceptible mechanism of inflammation in lung induced by genetic variants in NFκB1 (-94del>ins ATTG) or IκBα (2758G>A) to predict risk of COPD or lung cancer.
Authors:
Dongsheng Huang; Lei Yang; Yehua Liu; Yumin Zhou; Yuan Guo; Mingan Pan; Yunnan Wang; Yigang Tan; Haibo Zhong; Min Hu; Wenju Lu; Weidong Ji; Jian Wang; Pixin Ran; Nanshan Zhong; Yifeng Zhou; Jiachun Lu
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-16
Journal Detail:
Title:  Human genetics     Volume:  -     ISSN:  1432-1203     ISO Abbreviation:  Hum. Genet.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7613873     Medline TA:  Hum Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
School of Public Health, The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou, 510182, China.
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