association of fcγriia r131h polymorphism with idiopathic pulmonary fibrosis severity and progression协会fcγriia r131h多态性与特发性肺纤维化严重程度和进展.pdfVIP

Bournazos et al. BMC Pulmonary Medicine 2010, 10:51 /1471-2466/10/51 RESEARCH ARTICLE Open Access Association of FcgRIIa R131H polymorphism with idiopathic pulmonary fibrosis severity and progression 1,2 1 1 3 1,4 Stylianos Bournazos , Jacob Grinfeld , Karen M Alexander , John T Murchison , William A Wallace , Pauline McFarlane5 1,5 1,5 1 6* , Nikhil Hirani , A John Simpson , Ian Dransfield , Simon P Hart Abstract Background: A significant genetic component has been described for idiopathic pulmonary fibrosis (IPF). The R131H (rs1801274) polymorphism of the IgG receptor FcgRIIa determines receptor affinity for IgG subclasses and is associated with several chronic inflammatory diseases. We investigated whether this polymorphism is associated with IPF susceptibility or progression. Methods: In a case-control study, we compared the distribution of Fcg RIIa R131H genotypes in 142 patients with IPF and in 218 controls using allele-specific PCR amplification. Results: No differences in the frequency of Fcg RIIa genotypes were evident between IPF patients and control subjects. However, significantly impaired pulmonary function at diagnosis was observed in HH compared to RR homozygotes, with evidence of more severe restriction (reduced forced vital capacity (FVC)) and lower diffusing capacity for carbon monoxide (DLCO). Similarly, increased frequency of the H131 allele was observed in patients with severe disease (DLCO 40% predicted) (0.53 vs. 0.38; p = 0.03). Furthermore, the H131 allele was associated with progressive pulmonary fibrosis as determined by 10% drop in FVC and