Mucin 5B Promoter Polymorphism Is Associated With Susceptibility To Interstitial Lung Diseases In Male Of Chinese

Background and ObjectiveThe variation of G>T in the MUC5B promoter (rs35705950) has been associated with idiopathic pulmonary fibrosis (IPF) and familial interstitial pneumonia (FIP) in Caucasians, but no information is available regarding this variant in the Chinese population.Materials and Methods1. We recruited 405 patients with interstitial lung diseases (ILD), including 165 IPF patients, and 2043 healthy controls for genotyping the MUC5B gene in the Chinese population. One hundred three patients with pneumonia and 360 patients with autoimmune diseases (ADs) were recruited as patient controls.2. We screened for this variant in the promoter region of MUC5B gene in a case-control study with restriction fragment length polymorphism (RFLP) technique. Taqman SNP genotyping assay was used to repeat the genotypes of the investigated subjects.3. The BigDye terminators were used to sequence the PCR products from all the detected heterozygous and some of the homozygous subjects.Results1. Our results showed that the allele frequency for the minor-allele of the polymorphism rs35705950 was 0.66% in the healthy controls. The minor-allele frequencies were 2.22% in subjects with ILD,3.33% in subjects with idiopathic pulmonary fibrosis,0.7% in subjects with ADs and 0.49% in subjects with pneumonia.2. This variant frequency was only 0.66% in the healthy Chinese population, which was significantly decreased compared with the Caucasian populations. In the healthy Chinese groups, we found that the distribution of the minor-allele (T) was different with gender, the T allele frequency in the adult males (≥30 years old) was lower than that in the adult females (0.42% versus 1.04%, P= 0.030).3. The frequencies of the T allele were 3.33% and 2.22% in IPF and ILD patients, respectively, and these values were significantly higher than those of healthy controls (P= 0.001, OR= 4.332 for IPF, and P= 0.002, OR= 2.855 for ILD). Stratified analysis showed that the association of this variant in MUC5B with the risk for ILD was mainly in older male Chinese subjects. No difference was observed between patients with pneumonia, AD patients and healthy controls.ConclusionWe confirmed that the minor-allele frequency of the polymorphism rs35705950 in Chinese populations is lower than that in European Caucasians. This variant is significantly associated with the risk of ILD/IPF in Chinese subjects, although it might not be the main risk factor for IPF in the Chinese population. No association was observed between this variant of the MUC5B gene and the risk of secondary-ILD, autoimmune diseases or pneumonias. There might be other important risk factors in the pathogenesis of IPF in Chinese subjects.