An Association Between Angiotensin Converting Enzyme Genetic Polymorphism And Idiopathic Pulmonary Fibrosis

Objective: Idiopathic pulmonary fibrosis is a chronic inflammatory interstitial lung disease, which pathological change is usual interstitial pneumonia.The pathogenesy of the disease is still dimness. For the past few years, overseas literature report: Genetic gene can contribute the cause. Recent studies showed that angiotensin-converting enzyme (ACE) activity is increased in fibrotic tissues, and ACE inhibitors administered in vivo ameliorate fibrosis, suggesting that ACE may play a critical role. Fist, the aim of this study was to test hypothesis of an association between the polymorphism of ACE gene and idiopathic pulmonary fibrosis.Second, investigate the activity of ACE and angiotensinⅡ(AngⅡ) in IPF patients serum.Methods: IPF was diagnosed according to the national official statement which was established in 2002. The 64cases of IPF(men36 and women28, aged 42-78 years,mean age 58.4±7.3)are selected from the hospitalized patients. Patients with clinical evidence of cardiovascular disease,diabetic nephropathy and sarcoidosis were excluded. 54healthy subjects(men32 and women22 ),aged 48–67 years , mean age 55.8±4.3, recruited from blood donor served as control subjects. Determination of ACE genotypes: Genomic DNA was prepared from frozen peripheral blood by using standard procedures, and the D and I alleles were identified, on the basis of polymerase-chain-reaction(PCR) amplification of the respective fragments of the ACE gene. PCR products were separated by agarose gel electrophoresis, and DNA was visualized by ethidium bromide staining. Subjects were then classified, according to the absence or presence of the287 bp insertion in intron 16 of the ACE gene, as DD or II homozygotes or as ID heterozygotes. The activity of ACE and AngⅡwere determinated in all subjects serum. The frequent distribution of the alleles and genotypes were compared among all healthy subjects and all patients. The activity Of ACE and AngⅡwere compared among all all patients and healthy subjects. The analysis of all the materials used the SPSS12 statistics software,with the statistics difference of P<0.05. Measurement data was demonstrated by mean±standard deviation, interclass mean and measurement data were compared by t–test.The interclass frequency of the alleles and genotypes were compared by means of the chi square test.Results:1. Of 64 cases with IPF, 32(50.0%) were DD genotypes;19(29.7%) were ID genotypes; 13(20.3%) were II genotypes. However, of 54 cases with healthy subjects, 10(18.5%) were DD genotypes;31(57.4%) were ID genotypes; 13(24.1%) were II genotypes.It was different for distribution freguency of the genotypes beteen IPF subjects and healthy subjects(X2=14.288, P<0.05), demonstrating that the comprison of them was sense.2. There was an higher gene freguency of DD genotype of ACE gene in IPF subjects compared to healthy subjects (50.0% vs 18.5%, X2=12.662, P<0.05).3. The distribution of the ID genotypes between IPF subjects and healthy subjects was 29.7% vs 57.4%,( X2=9.216, P<0.05).The ID genotypes of IPF subjects was lower than healthy subjects.4. The distribution of the II genotypes was indiscriminate between IPF subjects and healthy subjects (20.3%vs 24.1%,X2=0.241, P > 0.05).5. Of 64 cases with IPF, 83(64.8%) were D alleles; howe- ver, of 53 cases with healthy subjects, 51(47.2%) were D alleles. There was an higher gene freguency of D allele of ACE gene in IPF subjects compared to healthy subjects (64.8% vs 47.2%, X2=7.412, P<0.05).6. Of 64 cases with IPF,45(35.2%) were I alleles; However, of 53 cases with healthy subjects, 57(52.8%) were I alleles. they were discriminate of I allele of ACE gene in IPF subjects comp- ared to healthy subjects (35.2% vs 52.8%, X2=7.412, P<0.05), The I allele of IPF subjects was lower than healthy subjects.7. The activity of serum ACE was 40.11±11.32 in IPF , however, The activity of serum ACE was 25.65±6.66 in healthy subjects. The activity of serum ACE was higher in IPF subjects compared to healthy subjects(t=8.601,P<0.05). 8. The level of serum AngⅡwas 57.74±20.68 in IPF , however, The level of serum AngⅡwas 46.13±16.62 in healthy subjects. The level of serum AngⅡwas higher in IPF subjects compared to healthy subjects(t=3.380,P<0.05)Conclusion:1.This study reports an association between the DD genotype and D allele of ACE and IPF, DD genotype and D allele are risk factors.2. The ID genotypes of IPF subjects was lower than healthy subjects, ID genotypes was a marker for redcued risk for IPF.3.The level of serum ACE and AngII was higher in IPF subjects compared to healthy subjects.