Genetic analysis of IREB2, FAM13A and XRCC5 variants in Chinese Han patients with chronic obstructive pulmonary disease

Guo, Yi; Lin, Hua; Gao, Kai; Xu, Hongbo; Deng, Xiong; Zhang, Qiang; Luo, Zhihua; Sun, Shenghua; Deng, Hao

doi:10.1016/j.bbrc.2011.10.042

Cited by 30 publications

(25 citation statements)

References 20 publications

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“…15 The subjects included in the above studies were all ever-smokers. However, in agreement with our study, one recent case-control study, which was also conducted in a Chinese Han population (cases ¼ 275, controls ¼ 434), found no association between IREB2 rs2568494 and COPD 16 in ever-smokers. The limit of the study is that only one SNP of IREB2 was investigated, so we can not get the information about other SNPs in IREB2 gene in that Chinese population.…”

Section: Association Of Ireb2 and Chrna3/5 With Copd In A Chinese Hansupporting

confidence: 92%

Association of IREB2 and CHRNA3/5 polymorphisms with COPD and COPD-related phenotypes in a Chinese Han population

Zhou

Yang

et al. 2012

J Hum Genet

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Genome-wide association studies and integrative genomics approaches have demonstrated significant associations between chronic obstructive pulmonary disease (COPD) and single-nucleotide polymorphisms (SNPs) in the chromosome 15q25 region that includes iron-responsive element binding protein 2 gene (IREB2) and CHRNA3/5 in non-Asian populations. We investigated whether IREB2 and CHRNA3/5 polymorphisms would be associated with COPD susceptibility and COPD-related phenotypes in a Chinese Han population. Eight SNPs (rs2568494, rs2656069, rs10851906, rs1964678, rs12593229, rs965604, rs13180, rs17483929) in IREB2 gene and four SNPs (rs16969968, rs1051730, rs938682, rs8034191) in or near CHRNA3/5 locus were genotyped in a case-control study (680 COPD patients and 687 controls). No significant associations were found between any of the SNPs and COPD in either former-smokers or current-smokers. Two SNPs (rs2656069 and rs10851906) in IREB2 were associated with COPD (P ¼ 0.045 and 0.032, respectively) in non-smoker. Four SNPs (rs1964678, rs12593229, rs965604 and rs13180) in IREB2 were associated with forced expiratory volume in 1 s (FEV 1 )% predicted and three SNPs (rs16969968, rs8034191 and rs1051730) in CHRNA3/5 were both associated with FEV 1 % predicted and FEV 1 /FVC in COPD cases (P range 0.007-0.050). The SNP rs8034191 near CHRNA3/5 locus was significantly associated with pack-years of smoking in COPD patients (P ¼ 0.033). We demonstrated IREB2 polymorphisms were associated with COPD in non-smoking subjects, and the effect of IREB2 gene on COPD may be independent from smoking and independent from CHRNA3/5 gene cluster. Besides, we confirmed that SNPs in these two gene loci were associated with pulmonary function and CHRNA3/5 polymorphism was associated with pack-year of smoking in COPD patients in the Chinese Han population.

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Section: Association Of Ireb2 and Chrna3/5 With Copd In A Chinese Hansupporting

confidence: 92%

Association of IREB2 and CHRNA3/5 polymorphisms with COPD and COPD-related phenotypes in a Chinese Han population

Zhou

Yang

et al. 2012

J Hum Genet

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“…The limitation of this study was that only one SNP was investigated and the COPD-related phenotypes were not evaluated. Therefore, information about other SNPs in XRCC5 in this Chinese population and about their association with COPD-related phenotypes was not available (Guo et al, 2011). The effect of a single polymorphism may be subtle, whereas the combination of several polymorphisms may be more predictive of an individual's response to an exposure.…”

Section: Discussionmentioning

confidence: 99%

Association of XRCC5 polymorphisms with COPD and COPD-related phenotypes in the Han Chinese population: a case-control cohort study

et al. 2014

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ABSTRACT. Genome-wide association studies (GWAS) and integrative genomic approaches have demonstrated significant associations between chronic obstructive pulmonary disease (COPD) and polymorphisms of the X-ray repair cross-complementing protein 5 gene (XRCC5) in non-Asian populations. We investigated whether XRCC5 polymorphisms might be associated with COPD susceptibility and COPD-related phenotypes in the Chinese Han population. Nine single nucleotide polymorphisms (SNPs) (rs3821104, rs12470053, rs207936, rs3770498, rs6704622, rs3770492, rs4674066, rs7573191, and rs207906) in the XRCC5 gene were genotyped in a case-control study including 680 COPD patients and 687 controls. To estimate the strength of association, odds ratios (ORs) were calculated and the effects of potentially confounding variables were tested by logistic regression analysis. The association between haplotypes 7071 Association of XRCC5 with COPD in the Chinese Han population ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (3): 7070-7078 (2014) and COPD outcome was also assessed. Our data identified that the SNP rs207936 was associated with COPD with an adjusted P value of 0.038, which was also found when analyzing only data of current smokers (P = 0.046). No significant associations were found between any of the SNPs and pulmonary function. Eight SNPs (rs3821104, rs12470053, rs207936, rs3770498, rs6704622, rs3770492, rs4674066, and rs7573191) showed strong linkage disequilibrium (R 2 ≥ 0.9). Two major haplotypes were observed and showed a significant difference between case and control groups (P = 0.0054 and 0.0081, respectively). The present study showed that the XRCC5 locus might be a contributor to COPD susceptibility in the Chinese Han population.

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“…We first examine the behavior of the algorithm on the smaller set of 2,441 subjects. In order to study the sensitivity of the method with respect to the main parameter (the number of the latent factors K ), we choose three SNPs associated with COPD (rs578776 [18]), nicotine dependence (rs17483721 [19]), and lung cancer (rs2568494 [6]), and evaluate the significance of the model fit for different values of K .…”

Section: Methodsmentioning

confidence: 99%

“…Standard GWAS identifies correlations between genetic variants and a single phenotype ( e.g., mostly disease vs. control). Although such analysis identified several variants relevant to COPD ( e.g., IREB2 on chromosome 15 [6]), such studies are likely incomplete. First, COPD is a mixture of diseases and therefore is unlikely to be explained by a single factor.…”

Section: Introductionmentioning

confidence: 99%

Spherical Topic Models for Imaging Phenotype Discovery in Genetic Studies

Batmanghelich¹,

Cho

Jose

et al. 2014

Bayesian and grAphical Models for Biomedical Imaging

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In this paper, we use Spherical Topic Models to discover the latent structure of lung disease. This method can be widely employed when a measurement for each subject is provided as a normalized histogram of relevant features. In this paper, the resulting descriptors are used as phenotypes to identify genetic markers associated with the Chronic Obstructive Pulmonary Disease (COPD). Features extracted from images capture the heterogeneity of the disease and therefore promise to improve detection of relevant genetic variants in Genome Wide Association Studies (GWAS). Our generative model is based on normalized histograms of image intensity of each subject and it can be readily extended to other forms of features as long as they are provided as normalized histograms. The resulting algorithm represents the intensity distribution as a combination of meaningful latent factors and mixing co-efficients that can be used for genetic association analysis. This approach is motivated by a clinical hypothesis that COPD symptoms are caused by multiple coexisting disease processes. Our experiments show that the new features enhance the previously detected signal on chromosome 15 with respect to standard respiratory and imaging measurements.

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Genetic analysis of IREB2, FAM13A and XRCC5 variants in Chinese Han patients with chronic obstructive pulmonary disease

Cited by 30 publications

References 20 publications

Association of IREB2 and CHRNA3/5 polymorphisms with COPD and COPD-related phenotypes in a Chinese Han population

Association of IREB2 and CHRNA3/5 polymorphisms with COPD and COPD-related phenotypes in a Chinese Han population

Association of XRCC5 polymorphisms with COPD and COPD-related phenotypes in the Han Chinese population: a case-control cohort study

Spherical Topic Models for Imaging Phenotype Discovery in Genetic Studies

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