Association of genetic polymorphisms of angiotensin converting enzyme and matrix metallo proteinase-1 with idiopathic pulmonary fibrosis

Abstract

To investigate the correlation between angiotensin converting enzyme (ACE) and matrix metallo proteinase (MMP)-1 gene polymorphisms and the risk of idiopathic pulmonary fibrosis (IPF) in a Han Chinese population from Hebei Province. Eighty-four IPF patients and 100 controls were enrolled from the Second Hospital of Hebei Medical University. Polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to detect ACE gene insertion/deletion (I/D) polymorphism and MMP-1 polymorphism respectively. The MMP-1 polymorphism was genotyped by DNA sequence analysis. Radioimmunoassay and ELISA were used to analyzed AngII, MMP-1 and TIMP-1 levels in IPF patients and healthy controls. There was a significant difference between the 2 groups in allele and genotype frequency distribution of ACE Insertion/Deletion polymorphism; frequency distribution of DD genotype and D allele of IPF patients were higher than those of the healthy control group (χ(2) = 11.227, 4.318, P < 0.05). There was no difference from different genders and ages on allele and genotype frequency distribution of ACE Insertion/Deletion polymorphism. (χ(2) = 0.03 - 1.069, P > 0.05). There was no significant difference between the 2 groups in genotype and allele frequency distribution of MMP-1 1G/2G polymorphism (χ(2) = 0.94 and 0.001, P > 0.05). The AngII levels from DD genotype of both IPF patients and healthy controls were the highest, followed by the DI genotype and the II genotype. The AngII level of any genotype for ACE Insertion/Deletion polymorphism in the IPF group was higher than that in the healthy control group (all P < 0.05). The serum level of AngII, MMP-1 and TIMP-1, as well as MMP-1/TIMP-1 ratio in the IPF group were higher than those in the healthy control group (all P < 0.05). The ACE polymorphism might be associated with IPF, and the serum level of AngII was affected not only by the genetic background of ACE insertion/deletion polymorphism but also the environmental factors. The MMP-1 1G/2G polymorphism might be weakly associated with IPF.