Angiotensin converting enzyme (ACE) gene polymorphism in sarcoidosis in relation to associated autoimmune diseases

Objectives. To investigate the significance of ACE gene insertion/deletion (I/D) polymorphism in the frequency of autoimmune manifestations in sarcoid osis. Design, In patients with sarcoidosis the ACE gene I/D polymorphism was dete cted with PCR on genomic DNA. The patients with sarcoidosis were divided ac cording to the presence (n = 30) or absence (n = 32) of autoimmune manifest ations. The former group was subdivided into thyroid autoimmunity (n = 10), gluten immune reactivity (rr = 10) and gastric autoimmunity (n = 17). Settings. The patients were recruited at the Department of Pulmonary Medici ne, and the study was conducted at the Department of Endocrinology, Univers ity of Lund, Malmo University Hospital, Malmo, Sweden, Subjects. Sixty-two patients with documented sarcoidosis (30 females, 32 ma les, median age/range at diagnosis of sarcoidosis 31.5/19-75 years, median age/range at study 47.5/22-81 years) were examined. A total of 107 healthy unrelated subjects without sarcoidosis (60 females, 47 males, median age/ra nge at study 58/40-82 years) served as controls. Results, S-ACE values were significantly increased in patients compared to controls (P = 0.00001). The same was true in the subgroup of sarcoidosis pa tients with associated autoimmunity compared with those with isolated sarco idosis (P = 0.0328). A significant association was seen between ACE gene po lymorphism (II, ID, DD genotypes) and S-ACE levels in both patients and con trols according to the order II < ID < DD. The observed genotype frequency distributions in the different study groups agreed the Hardy-Weinberg equil ibrium without significant differences between the patients and the control s. Within the group with autoimmune manifestations the DD genotype was sign ificantly over-represented in X-ray stage LU compared to the other X-ray st ages (P = 0.0181) and a significant increase in the DD genotype in X-ray st age III (P = 0.035) in the group with autoimmune manifestations compared to isolated sarcoidosis was detected. Conclusion, We confirmed that the S-ACE levels corresponded to the order II < ID < DD in patients with sarcoidosis as well as in healthy controls. S-A CE levels were significantly higher in sarcoidosis patients with autoimmune manifestations. The frequency of the DD genotype was significantly increas ed in patients with autoimmune manifestations and major granuloma mass (X-r ay stage III). The ACE D allele in its homozygous form may confer susceptib ility for autoimmune manifestations in sarcoidosis, possibly via the high l evels of S-ACE it encodes.