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Association of FcγRIIa R131H polymorphism with idiopathic pulmonary fibrosis severity and progression.

Bournazos S, Grinfeld J, Alexander KM, Murchison JT, Wallace WA, McFarlane P, Hirani N, Simpson AJ, Dransfield I, Hart SP - BMC Pulm Med (2010)

Bottom Line: 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/or > 15% fall in DLCO at 12 months after baseline (0.48 vs. 0.33; p = 0.023).

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Edinburgh/Medical Research Council Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, UK.

ABSTRACT

Background: A significant genetic component has been described for idiopathic pulmonary fibrosis (IPF). The R131H (rs1801274) polymorphism of the IgG receptor FcγRIIa 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 FcγRIIa R131H genotypes in 142 patients with IPF and in 218 controls using allele-specific PCR amplification.

Results: No differences in the frequency of FcγRIIa 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/or > 15% fall in DLCO at 12 months after baseline (0.48 vs. 0.33; p = 0.023).

Conclusions: These findings support an association between the FcγRIIa R131H polymorphism and IPF severity and progression, supporting the involvement of immunological mechanisms in IPF pathogenesis.

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R131H polymorphism is associated with disease progression. Serial lung function measurements were obtained for 121 IPF patients 12 months following baseline to assess disease progression. FVC (forced vital capacity) displayed a significant fall in HH, but not RR or RH patients. Data are presented as the mean percent change in actual values 12 months following baseline ± 95% confidence intervals (CI). *p < 0.01 RR vs. HH.
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Figure 2: R131H polymorphism is associated with disease progression. Serial lung function measurements were obtained for 121 IPF patients 12 months following baseline to assess disease progression. FVC (forced vital capacity) displayed a significant fall in HH, but not RR or RH patients. Data are presented as the mean percent change in actual values 12 months following baseline ± 95% confidence intervals (CI). *p < 0.01 RR vs. HH.

Mentions: Furthermore, a significant reduction in FVC was observed in the first 12 months in HH homozygotes, compared to homozygous and heterozygous carriers of the R allele (Figure 2). In contrast, no major change in DLCO was evident between the three R131H genotypes, despite the lower baseline DLCO values observed in HH patients (data not shown). In summary, all these findings suggest that the FcγRIIa R131H polymorphism represents a genetic risk factor for IPF disease progression.


Association of FcγRIIa R131H polymorphism with idiopathic pulmonary fibrosis severity and progression.

Bournazos S, Grinfeld J, Alexander KM, Murchison JT, Wallace WA, McFarlane P, Hirani N, Simpson AJ, Dransfield I, Hart SP - BMC Pulm Med (2010)

R131H polymorphism is associated with disease progression. Serial lung function measurements were obtained for 121 IPF patients 12 months following baseline to assess disease progression. FVC (forced vital capacity) displayed a significant fall in HH, but not RR or RH patients. Data are presented as the mean percent change in actual values 12 months following baseline ± 95% confidence intervals (CI). *p < 0.01 RR vs. HH.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2958991&req=5

Figure 2: R131H polymorphism is associated with disease progression. Serial lung function measurements were obtained for 121 IPF patients 12 months following baseline to assess disease progression. FVC (forced vital capacity) displayed a significant fall in HH, but not RR or RH patients. Data are presented as the mean percent change in actual values 12 months following baseline ± 95% confidence intervals (CI). *p < 0.01 RR vs. HH.
Mentions: Furthermore, a significant reduction in FVC was observed in the first 12 months in HH homozygotes, compared to homozygous and heterozygous carriers of the R allele (Figure 2). In contrast, no major change in DLCO was evident between the three R131H genotypes, despite the lower baseline DLCO values observed in HH patients (data not shown). In summary, all these findings suggest that the FcγRIIa R131H polymorphism represents a genetic risk factor for IPF disease progression.

Bottom Line: 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/or > 15% fall in DLCO at 12 months after baseline (0.48 vs. 0.33; p = 0.023).

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Edinburgh/Medical Research Council Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, UK.

ABSTRACT

Background: A significant genetic component has been described for idiopathic pulmonary fibrosis (IPF). The R131H (rs1801274) polymorphism of the IgG receptor FcγRIIa 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 FcγRIIa R131H genotypes in 142 patients with IPF and in 218 controls using allele-specific PCR amplification.

Results: No differences in the frequency of FcγRIIa 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/or > 15% fall in DLCO at 12 months after baseline (0.48 vs. 0.33; p = 0.023).

Conclusions: These findings support an association between the FcγRIIa R131H polymorphism and IPF severity and progression, supporting the involvement of immunological mechanisms in IPF pathogenesis.

Show MeSH
Related in: MedlinePlus