Complement Receptor 1 Gene Polymorphisms Are Associated with Idiopathic Pulmonary Fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrotic disorder underlain by aberrant wound healing of repeated lung injury. Environmental triggers and genetic background are likely to act as modifiers of the fibrotic response. Erythrocyte complement receptor 1 is a membrane protein mediating the transport of immune complexes to phagocytes. Three gene polymorphisms are related to the erythrocyte surface density of complement receptor 1 molecules, which in turn are related to the rate of immune complexes' clearance. There is evidence of association between sarcoidosis and the complement receptor 1 gene. We wondered whether IPF is associated with the complement receptor 1 gene alleles coding for a reduced molecule/erythrocyte ratio. We studied 74 patients and 166 control subjects. Three polymorphic sites of the gene, A3650G exon 22, HindIII RFLP intron 27, and C5507G exon 33, were analyzed and found to be in linkage disequilibrium. The GG genotype for the C5507G exon 33 polymorphism was significantly more common in patients with IPF than in control subjects (odds ratio = 6.232, 95% confidence interval = 2.198-18.419, p = 0.00023). The significant difference was found in both sexes. These findings agree with speculations on the role of the complement receptor 1 gene in idiopathic pulmonary fibrosis.

Angiotensinogen gene G-6A polymorphism influences idiopathic pulmonary fibrosis disease progression

“…The pathophysiology of IPF is likely to be determined by multiple genetic factors that each contribute to disease development [10,23]. Following the evolving hypothesis, which suggests that IPF is a consequence of impaired wound healing involving the epithelial/fibroblast pathway [2], many candidate genes for growth factors, as well as other molecular mediators implicated in this extensive process, have been evaluated [24][25][26][27][28]. The first candidate genes to be analysed in IPF patients were involved in inflammatory responses.…”

CR1 genotype and haplotype involvement in coronary artery disease: The pivotal role of hypertension and dyslipidemia

“…The Pro1827Arg C allele has been reported to be associated with the intron 27 HindIII RFLP H allele, whereas the Pro1827Arg G allele has been associated with the intron 27 HindIII RFLP L allele in Caucasians (16,43). These alleles are correlated respectively with either a high (H) or low (L) CR1/E ratio.…”

Idiopathic pulmonary fibrosis: current understanding of the pathogenesis and the status of treatment

“…22 Familial IPF may be inherited as an autosomal dominant trait with variable penetrance, but this speculation has not been supported in each instance. 4,[23][24][25][26] Inherited abnormalities in surfactant proteins 24 and the interleukin-1 (IL-1) receptor antagonist, 25 as well as polymorphism of the tumour necrosis factor-alpha gene 25 and complement receptor 1 gene, 26 have been associated with some cases of IPF, which suggests that obscure biochemical aberrancies can lead to an IPF-like condition.…”