The MUC5B variant is associated with idiopathic pulmonary fibrosis but not with systemic sclerosis interstitial lung disease in the European Caucasian population

Abstract

A polymorphism on the MUC5B promoter (rs35705950) has been associated with idiopathic pulmonary fibrosis (IPF) but not with systemic sclerosis (SSc) with interstitial lung disease (ILD). We genotyped the MUC5B promoter in the first 142 patients of the French national prospective cohort of IPF, in 981 French patients with SSc (346 ILD), 598 Italian patients with SSc (207 ILD), 1383 French controls and 494 Italian controls. A meta-analysis was performed including all American data available. The T risk allele was present in 41.9% of the IPF patients, 10.8% of the controls (P = 2 × 10(-44)), OR 6.3 [4.6-8.7] for heterozygous patients and OR 21.7 [10.4-45.3] for homozygous patients. Prevalence of the T allele was not modified according to age, gender, smoking in IPF patients. However, none of the black patients with IPF presented the T allele. The prevalence of the T risk allele was similar between French (10%) and Italian (12%) cohorts of SSc whatever the presence of an ILD (11.1% and 13.5%, respectively). Meta-analysis confirmed the similarity between French, Italian and American cohorts of IPF or SSc-ILD. This study confirms 1) an association between the T allele risk and IPF, 2) an absence of association with SSc-ILD, suggesting different pathophysiology.

Figure 1. Distribution of clinical characteristic according to the MUC5B genotype.

(A) Distribution of age according to genotype. The centre line of the box denotes the mean, the extremes of the box the interquartile range and the bars the highest and lowest values. (B) Distribution of the gender according to the genotype. Percentage of men is represented in grey; percentage of women is represented in white with black dots. NS non significant. (C) Distribution of the smoking status according to the genotype. Percentage of never smokers is represented in grey, percentage of past smokers is represented in white, and percentage of active smokers is represented in black. (D) Distribution of the ethnic status according to the genotype. Percentage of European is represented in white, percentage of North African is represented in grey, and percentage of black patients is represented in dark. * P = 0.0008.

Figure 2. Meta-analysis of the MUC5B rs35705950 T allele risk in the three American cohorts and the French cohort of idiopathic pulmonary fibrosis (IPF).

Forrest plots of the meta-analysis of the association of the MUC5B rs35705950 T polymorphism and IPF. Bars represent the 95% interval.

Figure 3. Meta-analysis of the MUC5B rs35705950 T allele risk in the two European (French and Italian) cohorts and the American cohort of systemic sclerosis (SSc).

Forrest plots of the meta-analysis of the association of the MUC5B rs35705950 T polymorphism and (A) all SSc and (B) SSc with interstitial lung disease. Bars represent the 95% interval.