Chest
Volume 147, Issue 2, February 2015, Pages 460-464
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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 Ancestries

https://doi.org/10.1378/chest.14-0867Get rights and content

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.

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

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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.

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