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Original Research: Diffuse Lung Disease |

The MUC5B Promoter Polymorphism Is Associated With Idiopathic Pulmonary Fibrosis in a Mexican Cohort but Is Rare Among Asian AncestriesPolymorphism in Idiopathic Pulmonary Fibrosis

Anna L. Peljto, DrPH; Moises Selman, MD, FCCP; Dong Soon Kim, MD; Elissa Murphy, MS; Laura Tucker, BS; Annie Pardo, PhD; Jung Su Lee, MD; Wonjun Ji, MD; Marvin I. Schwarz, MD, FCCP; Ivana V. Yang, PhD; David A. Schwartz, MD; Tasha E. Fingerlin, PhD
Author and Funding Information

From the Department of Medicine (Drs Peljto, M. I. Schwarz, Yang, and D. A. Schwartz and Ms Murphy), Department of Immunology (Dr D. A. Schwartz), and Department of Epidemiology (Dr Fingerlin), University of Colorado Denver, Denver, CO; Instituto Nacional de Enfermedades Respiratorias (Dr Selman), Mexico City, Mexico; Asan Medical Center (Drs Kim, Lee, and Ji), University of Ulsan College of Medicine, Seoul, South Korea; Yale University (Ms Tucker), New Haven, CT; Universidad Nacional Autonoma de Mexico (Dr Pardo), Mexico City, Mexico; and Department of Medicine (Drs M. I. Schwarz and D. A. Schwartz), National Jewish Health, Denver, CO.

CORRESPONDENCE TO: Anna L. Peljto, DrPH, University of Colorado, School of Medicine, 12631 E 17th Ave, MS B178, Aurora, CO 80045; e-mail: anna.peljto@ucdenver.edu


Drs D. A. Schwartz and Fingerlin contributed equally to the manuscript.

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.


Chest. 2015;147(2):460-464. doi:10.1378/chest.14-0867
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BACKGROUND:  Polymorphisms in the MUC5B promoter, TOLLIP, and nine additional genetic loci have been associated with idiopathic pulmonary fibrosis (IPF) within non-Hispanic white populations. It is unknown whether these variants account for risk of IPF in other racial/ethnic populations. We conducted a candidate single nucleotide polymorphism (SNP) association study in cohorts of Mexican and Korean patients with IPF.

METHODS:  We chose 12 SNPs from 11 loci that are associated with IPF among non-Hispanic whites and genotyped these SNPs in cohorts of Mexican (83 patients, 111 control subjects) and Korean (239 patients, 87 control subjects) people. Each SNP was tested for association with IPF, after adjusting for age and sex.

RESULTS:  The MUC5B promoter SNP rs35705950 was associated with IPF in the Mexican (OR = 7.36, P = .0001), but not the Korean (P = .99) cohort. The SNP in IVD (chromosome15, rs2034650) was significantly associated with pulmonary fibrosis in both the Mexican (OR = 0.40, P = .01) and Korean (OR = 0.13, P = .0008) cohorts. In the Korean cohort, there were no other variants associated with disease. In the Mexican cohort, SNPs on chromosomes 3, 4, and 11 were also associated with disease.

CONCLUSIONS:  The strongest identified genetic risk factor for IPF among the non-Hispanic white population, the MUC5B promoter polymorphism, is also a strong risk factor in a Mexican population, but is very rare in a Korean population. The majority of genetic variants that account for risk of IPF in groups other than non-Hispanic whites are unknown. Hispanic and Asian populations should be studied separately to identify genetic risk loci for IPF.


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