Association between the MUC5B Promoter Polymorphism rs35705950 and Idiopathic Pulmonary Fibrosis: a Meta-analysis

and Trial Sequential Analysis in Caucasian and Asian Populations

Qing-Qing Zhu, MD, Xin-Lin Zhang, MD,Si-Min Zhang, MM, Shao-Wen Tang, PhD, Hai-Yan Min, PhD, Long Yi, PhD, Biao Xu, MD, PhD, Yong Song,

MD, PhD

Search strategy in PubMed:(“Idiopathic pulmonary fibrosis” or “IPF” or “Usual interstitial pneumonia” or “UIP” or “Cryptogenic FibrosingAlveolitis”

or “Hamman Rich Disease” or “Fibrocystic Pulmonary Dysplasia”) and (rs35705950 or (("MUC5B" or "mucin 5B" or "MG1" or "MUC5" or "MUC9" or

"MUC-5B") and ("polymorphism" or "mutation" or "variation")))

Association between the MUC5B Promoter Polymorphism rs35705950 and Idiopathic Pulmonary Fibrosis: a Meta-analysis and Trial Sequential Analysis in Caucasian and Asian PopulationsQing-Qing Zhu, MD, Xin-Lin Zhang, MD,Si-Min Zhang, MM, Shao-Wen Tang, PhD, Hai-Yan Min, PhD, Long Yi, PhD, Biao Xu, MD, PhD, Yong Song,

MD, PhD

Table S1.Quality assessment of studies using the Newcastle-Ottawa Scale (NOS), and the definitions of IPF patients and controls.

First author Year Ethnicity Selection Comparabilit

y

Exposure Total IPF patients Controls

Seibold, et al 2011 Caucasian 4 1 3 8 The 2001 American Thoracic Society/European

Respiratory Society consensus (A high resolution

computerized tomography (HRCT) scan was

required to show definite or probable IIP

according to predefined criteria, a surgical lung

biopsy was obtained in 46% of affected

subjects.)

A COPD case-control cross-sectional study,

excluded self-reported or had a physician-diagnosis

of idiopathic pulmonary fibrosis or another

interstitial lung disease.

Borie, et al 2013 Caucasian 3 1 3 7 The 2001 American Thoracic Society/European

Respiratory Society consensus (either surgical

biopsy or a characteristic CT scan pattern)

Healthy unrelated individuals who were ethnically

matched.

Noth, et al 2013 Caucasian 4 1 3 8 The 2000 and 2011 guidelines from the American

Thoracic Society and European Respiratory

Society (A high-resolution CT scan that showed

definite or probable usual interstitial pneumonitis

was necessary for inclusion. A surgical lung

biopsy sample to confirm usual interstitial

Healthy individuals free of lung diseases based on

ICD9 coding and medical record review.

pneumonitis could be obtained if the diagnosis

was in doubt, a surgical lung biopsy was

obtained in 37.3% of subjects)

Stock, et al 2013 Caucasian 4 2 3 9 The 2001 criteria of the American Thoracic

Society/European Respiratory Society

Healthy blood donors based on a self-administered

questionnaire and by the routine laboratory

investigations performed on blood donors.

Horimasu, et al 2014 Asian 4 1 3 8 The 2001 criteria of the American Thoracic

Society/European Respiratory Society

Healthy subjects underwent pulmonary function

tests and chest X-ray studies, excluded those with

apparent lung disease such as interstitial lung

diseases (ILD) or chronic obstructive pulmonary

disease.

Horimasu, et al 2014 Caucasian 4 1 3 8 The criteria of the American Thoracic

Society/European Respiratory Society in 2002

Healthy subjects underwent pulmonary function

tests and chest X-ray studies, excluded those with

apparent lung disease such as interstitial lung

diseases (ILD) or chronic obstructive pulmonary

disease.

Wang, et al 2014 Asian 4 2 3 9 The 2011 American Thoracic Society/European

Respiratory Society International Consensus,

exclusion of the known causes of interstitial lung

disease (clinical features and HRCT evaluation,

and ahistopathologic diagnosis was made for the

cases with an atypical HRCT image)

Healthy individuals who were undergoing a routine

physical examination at the same hospital

Peljto, et al. 2015 Caucasian 3 2 3 8 The 2011 American Thoracic Society/European

Respiratory Society International Consensus

Guidelines

NA

Peljto, et al. 2015 Asian 3 2 3 8 The 2011 American Thoracic Society/European

Respiratory Society International Consensus

Guidelines

Control subjects with at least 5 years of smoking

history (former and current) and normal pulmonary

function tests were recruited from a smoking

cessation program at the same institute, and

nonsmoking control subjects were unrelated healthy

volunteers.

The Newcastle-Ottawa Scale (NOS) assesses the study quality in 3 categories: selection, comparability, and exposure. A maximum of 4 stars could be given to

selection items, 2 stars to comparability section and 3 stars to Exposure category. NA=not available.

Figure S1. Trial sequential analysis of rs35705950 polymorphism and IPF risk using the allelic model (T allele versus G allele) in Caucasian population.

Figure S2. Trial sequential analysis of rs35705950 polymorphism and IPF risk using the allelic model (T allele versus G allele) in Asian population.

Figure S3. Funnel plot assessing evidence of publication bias from the eligible studies using the allelic model (T allele versus G allele).

Figure S4. Funnel plot assessing evidence of publication bias from the eligible studies using the genotypic model (GT genotype versus GG genotype).

Figure S5. Trial sequential analysis of rs35705950 polymorphism and IPF risk using the genotypic model (GT genotype versus GG genotype) in Caucasian population.

Figure S6. Trial sequential analysis of rs35705950 polymorphism and IPF risk using the genotypic model (GT genotype versus GG genotype) in Asian population.