Association of rs3750920 polymorphism in TOLLIP with clinical characteristics of fibrosing interstitial lung diseases in Japanese

Abstract

TOLLIP polymorphism has been implicated in the development and prognosis of idiopathic pulmonary fibrosis (IPF), mainly in whites. However, ethnic differences in the characteristics of other interstitial pneumonia (non-IPF) subtypes are unclear. We evaluated the association between the rs3750920 genotype and the clinical characteristics of Japanese patients with fibrosing interstitial lung diseases (ILD). We genotyped 102 patients with fibrosing ILD (75 IPF and 27 non-IPF patients) and analyzed the interaction between the rs3750920 genotype distribution and their clinical characteristics. The overall frequencies of the C/C, C/T, and T/T genotypes were 69%, 25%, and 6%, respectively. The proportion of minor T allele carriers was larger in IPF patients than in non-IPF patients (37% vs. 15%, P = 0.031). In addition, survival at 3 years was significantly better for carriers than for non-carriers of the T allele. There was no significant association between genotype distribution and change in pulmonary function after introduction of antifibrotic agents. The frequency of the minor T allele of rs3750920 was low in Japanese patients with fibrosing ILD, particularly in non-IPF patients. Carriers of the minor T allele had better survival than non-carriers. Presence of the T allele might thus be an indicator of better outcomes for fibrosing ILD.

Toll interacting protein (TOLLIP) increases in fibrotic lung tissue of connective tissue disease-associated interstitial lung disease and is associated with clinical outcome

“…In another retrospective study of patients with IPF and IPAF, rs3750920 T/T showed an increased frequency in the positive ANA group, in which NAC exposure seemed to be bene cial for transplant-free survival [35]. In a Japanese population study, the frequency of the minor T allele of rs3750920 was low in patients with brotic ILD, especially in non-IPF patients, which might be an indicator of better survival in these patients [14]. In an inception cohort study on early rheumatoid arthritis (RA), TOLLIP rs111521887 was associated with pulmonary brosis in RA [36].…”

“…Dysregulation of TOLLIP is associated with various diseases, such as Parkinson's disease, Alzheimer's disease, in ammatory bowel disease, myocardial hypertrophy, and idiopathic pulmonary brosis [9][10][11][12][13]. Several studies have focused on the association between genetic variants of TOLLIP and susceptibility, treatment response, and the progression of patients with CTD-ILD [14][15]. However, the location of TOLLIP in the lung tissue of patients with CTD-ILD has not yet been established.…”

TogoVar: A comprehensive Japanese genetic variation database

“…TogoVar is becoming recognized as shared infrastructure data. The purposes for its use are variant prioritization 34 , determination of whether a variant of interest is known or unknown 35 , and comparison of allele frequencies in TogoVar with those of disease groups or non-Japanese populations 36 , 37 .…”