Chest
Original Research: Diffuse Lung DiseaseThe MUC5B Promoter Polymorphism Is Associated With Idiopathic Pulmonary Fibrosis in a Mexican Cohort but Is Rare Among Asian Ancestries
Section snippets
Candidate SNPs
We chose 12 SNPs from 11 loci previously reported to be common in the non-Hispanic white population and associated with pulmonary fibrosis.1, 2, 3 The MUC5B promoter polymorphism was originally reported to be associated with IPF by Seibold et al,3 nine loci outside of the MUC5B locus were reported by Fingerlin et al,1 and two SNPs within TOLLIP were reported by Noth et al.2 We chose not to genotype a third reported SNP within TOLLIP, since it was found to be in high linkage disequilibrium (r2 =
Results
The Mexican and Korean patients were similar in age, proportion of women, and diffusion capacity of carbon monoxide; however, Korean patients were more likely to have a history of smoking (P = .004) and better FVC at the time of diagnosis (P < .0001) compared with the Mexican patients (Table 1).
The MUC5B promoter polymorphism was the most strongly associated variant in the Mexican cohort (rs35705950 in MUC5B; OR = 7.36, P = .0001), as has been reported for non-Hispanic white cohorts.
Discussion
We found that the strongest genetic risk factor for pulmonary fibrosis, rs35705950 in the promoter of MUC5B, identified in non-Hispanic white populations, is also a risk factor in Hispanic populations, but is rare among Asian cases of IPF. This suggests that findings related to IPF and MUC5B or future treatments that target MUC5B may apply to Hispanic patients, in addition to non-Hispanic white patients. In the Korean cohort, the MUC5B promoter polymorphism was extremely rare among patients
Acknowledgments
Author contributions: A. L. P. had full access to the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. A. L. P., M. I. S., I. V. Y., D. A. S., and T. E. F. contributed to the study design; M. S., D. S. K., A. P., J. S. L., and W. J. recruited patients and conducted clinical evaluations; E. M. and L. T. performed the laboratory work; A. L. P., L. T., and T. E. F. analyzed data; M. I. S., I. V. Y., D. A. S., and T. E. F. contributed
References (17)
- et al.
Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study
Lancet Respir Med
(2013) - et al.
Ethnic and racial differences in the presence of idiopathic pulmonary fibrosis at death
Respir Med
(2012) - et al.
Racial and ethnic disparities in idiopathic pulmonary fibrosis: A UNOS/OPTN database analysis
Am J Transplant
(2006) - et al.
Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis
Nat Genet
(2013) - et al.
A common MUC5B promoter polymorphism and pulmonary fibrosis
N Engl J Med
(2011) - et al.
Telomerase mutations in families with idiopathic pulmonary fibrosis
N Engl J Med
(2007) - et al.
Adult-onset pulmonary fibrosis caused by mutations in telomerase
Proc Natl Acad Sci U S A
(2007) - et al.
A variant in the promoter of MUC5B and idiopathic pulmonary fibrosis
N Engl J Med
(2011)
Cited by (94)
First ever characterisation of the effects of short telomeres in a Singapore interstitial lung disease cohort
2024, Respiratory InvestigationEmerging opportunities to treat idiopathic pulmonary fibrosis: Design, discovery, and optimizations of small-molecule drugs targeting fibrogenic pathways
2023, European Journal of Medicinal ChemistryKnowledge gaps in fibrotic interstitial lung disease in pan-Asian populations: data not missing at random?
2023, The Lancet Respiratory MedicineTelomeres and lung
2022, Revue des Maladies Respiratoires
FUNDING/SUPPORT: This research was supported by the National Heart, Lung, and Blood Institute [R01-HL095393, R01-HL097163, P01-HL092870, and RC2-HL101715] and the Veterans Administration [1I01BX001534]. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.