MUC5B, telomere length and longitudinal quantitative interstitial lung changes: the MESA Lung Study.

Area of Science:

• Pulmonary Medicine
• Genetics
• Radiology

Background:

• The MUC5B promoter variant and telomere length are known risk factors for pulmonary fibrosis.
• Their association with longitudinal quantitative changes in the lung interstitium is not well understood.

Purpose of the Study:

• To investigate the association of the MUC5B risk allele and telomere length with longitudinal changes in lung interstitial abnormalities.
• To examine the impact of these changes on mortality and interstitial lung disease (ILD) risk.

Main Methods:

• Utilized data from the Multi-Ethnic Study of Atherosclerosis (MESA) including high-attenuation areas (HAAs) from CT scans (n=4552).
• Employed linear mixed-effects models to assess the relationship between MUC5B genotype, telomere length, and HAAs over time (Examinations 1-6).
• Used joint models to link longitudinal HAA changes with mortality and ILD outcomes.

Main Results:

• The MUC5B risk allele (T) was associated with a 2.60% increase in HAAs per decade.
• This association was more pronounced in individuals with shorter telomere lengths (interaction p=0.008).
• Each 1% annual increase in HAAs correlated with a 7% higher mortality risk and a 34% higher ILD risk.

Conclusions:

• Longitudinal increases in lung interstitial abnormalities, indicated by HAAs, are associated with the MUC5B risk allele.
• Progressive interstitial changes independently predict increased risk of death and interstitial lung disease (ILD).