Toll interacting protein (TOLLIP) gene polymorphisms in patients with systemic sclerosis (SSc) associated interstitial lung disease (ILD): association with outcome and survival.

<bold>Background:</bold> Pulmonary fibrosis is a leading cause of death in patients with Systemic sclerosis (SSc). Single nucleotide polymorphisms (SNPs) within Toll interacting protein (<italic>TOLLIP</italic>) coding gene have been associated with progression and prognosis of Idiopathic Pulmonary Fibrosis. <bold>Aim:</bold> of the present study was to investigate the association of <italic>TOLLIP</italic> SNPs with the presence, severity and outcome of ILD in patients with SSc. <bold>Methods:</bold> 106 consecutive SSc patients (77 Female) with (N=53) and without ILD (N=53) and 60 healthy controls (HC) (35 Female) were genotyped for two SNPs within <italic>TOLLIP</italic> (rs3750920, rs5743890) by using TaqMan^TM SNP Genotyping Assay (Thermo Fischer Scientific, USA). <bold>Results:</bold> Both SNPs were in high linkage disequilibrium (D’ 0.9993, p<0.0001). The <italic>TOLLIP</italic> rs5743890 minor Allele (C) was slightly overrepresented in HC than in SSc patients (17 vs 9%, p=0.023), while no differences were seen between SSc with or without ILD. In the over-dominant model, the homozygote alleles of rs5743890 were significantly overrepresented in SSc patients compared to HC (85 vs 64%, p=0.006). SSc-ILD patients carrying rs5743890 T/C genotype had a tendentially worse survival (158 vs 213 months) and a significantly shorter time to disease progression (30 vs 114 months) than patients with homozygote genotype (p=0.258 and p=0.025, respectively). <bold>Conclusion:</bold> <bold>TOLLIP</bold> SNP rs5743890 genotype distribution seems to differ in SSc patients compared to HC. The rs5743890 heterozygote genotype may be associated with an increased risk of progression and worse survival in patients with SSc-ILD.