| Objective: To explore the hereditary susceptibility of idiopathic pulmonary fibrosis (IPF) by studying the erythrocyte CR1 genomic density polymorphism and A3650G sites polymorphism, and reveal the association between CR1 genomic density polymorphism and the levels of E-CR1 in IPF patients,so as to investigate the pathogenesy of idiopathic pulmonary fibrosis.Methods: The investigation was designed as a case–control association study with IPF. The subjects were composed of two groups, the patient group consisted of 64 han people's subjects(36 males and 28 females) with IPF (mean age 58.4±7. 3 years),which diagnostic confirmation was based on a detailed clinical assessment .Subjects were excluded from the study if they had a secondary cause of pulmonary fibrosis or if they had manifestations of acute infection, cancer, embolism, congestive heart failure, diabetes, peptic ulcer, severe osteoporosis,tuberculosis. The control group comprised ethnically matched healthy control subjects, a total of 54 healthy subjects (32 males and 22 females) were recruited, In addition none of them were suffering from any infection ,autoimmune, inflammatory disorders and any using immunodepressant , and the mean age in this group was 55.8±4.3 years. Venous blood of the IPF patients and control individuals was collected in EDTA. Genomic DNA was isolated from peripheral blood with the use of standard methods. HindⅢrestriction enzyme and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to detect the genotype of the CR1 genomic density polymorphism and A3650G sites polymorphism in both the IPF patients and the healthy controls. Expression of CR1 on RBC surface in both the IPF patients and the healthy controls was measured by flowcytometry.Results:1 To compare HindⅢpolymorphism in the patients group and the normal group, frequencies of HH , HL and LL genotypes were 21(32.8%), 30(46.9%) and 13(20.3%) in the IPF group ,however 39 ( 72.2 %),14 ( 25.9 % ) and l ( 1.9 % ) in the control group , respectively . A significant difference was found in the frequency distribution of CR1 genotype between two groups(χ~2=15.516,P=0.000<0.05). The HH genotype for the HindⅢpolymorphism was lower in patients with IPF than in control subjects (P=0.022<0.05). The HL genotype for the HindⅢpolymorphism was significantly higher in patients with IPF than in control subjects (P=0.019<0.05), and the LL genotype for the HindⅢpolymorphism was significantly lower in patients with IPF than in control subjects (P=0.013<0.05).HL+LL genotype for the HindⅢpolymorphism was more common in patients with IPF compared to controls with an OR = 5.32 (95% CI, 2.4660–11.4771; p =0.000< 0.05).2 Within the group of sixty four IPF subjects, number and percentage distribution for A and G allel were found to be 57 (89.1%)and 7(10.9%), respectively. and within the group of fifty four normal individuals, number and percentage distribution for A and G allel were found to be 51 (94.4%)and 3(5.6%), respectively. There was no difference from distribution of CR1 gene A3650G wits polymorphism in two groups(χ~2=1.094,P=0.296>0.05).3 Comparison of the mean E-CR1 levels in the IPF patients revealed the E-CR1 levels in patients to be significantly lower than normals. The mean CR1/E numbers observed in the IPF patients was 13.46±3.86, and the mean CR1/E in normal individuals was 24.33±3.84 (t=15.288, p=0.000<0.05 vs IPF group).4 The levels of E-CR1 in both IPF patients and healthy controls HH genotype for E-CR1 HindⅢ-RFLP were significantly higher than HL genotype for E-CR1 HindⅢ-RFLP(t=9.973,P=0. 000<0.05), and the levels of E-CR1 in both groups HL genotype for E-CR1 HindⅢ-RFLP were significantly higher than LL genotype for E-CR1 HindⅢ-RFLP(t=9.973,P=0. 000<0.05). These results revealed that the levels of E-CR1 was determined to the genetic factors of E-CR1 HindⅢ-RFLP.5 The levels of E-CR1 in IPF patients HH genotype for E-CR1 HindⅢ-RFLP were significantly lower compared to healthy controls having the same allele (t=14.297,P=0.000<0.05). The levels of E-CR1 in IPF patients HL genotype for E-CR1 HindⅢ-RFLP were significantly lower compared to healthy controls having the same allele.(t=12.221, P=0.000<0.05).and the levels of E-CR1 in IPF patients LL genotype for E-CR1 HindⅢ-RFLP were also lower compared to healthy controls having the same allele. (t=2.534, P=0.000<0.05). These results revealed that the levels of E-CR1 was also determined to the acquired predisposition.Conclusion:1 There is an association between the erythrocyte CR1 genomic density polymorphism and IPF, meanwhile, the levels of CR1 on erythrocytes was not only determined to the genetic factors of E-CR1 HindⅢ-RFLP but also determined to the acquired predisposition. In this study, we suggest that HL and LL genotype of CR1 gene may act as important in determining an susceptibility to development of IPF, and indicated that L allele might predispose an individual to develop IPF.2 The reduction of CR1/E, which could degrate the clearance of circulating immune complexes, observed in patients may be a phenomenon which pulmonary interstitial alterations and structure disorders with IPF, and that the degression and impairment of erythrocyte immune function could play a important role in the pathogenesis of IPF. |
PDF Full Text Request