Angiotensin converting enzyme (ACE) gene polymorphism in sarcoidosis in relation to associated autoimmune diseases.
OBJECTIVE
To investigate the significance of ACE gene insertion/deletion (I/D) polymorphism in the frequency of autoimmune manifestations in sarcoidosis.


METHODS
In patients with sarcoidosis the ACE gene I/D polymorphism was detected with PCR on genomic DNA. The patients with sarcoidosis were divided according to the presence (n = 30) or absence (n = 32) of autoimmune manifestations. The former group was subdivided into thyroid autoimmunity (n = 10), gluten immune reactivity (n = 10) and gastric autoimmunity (n = 17).


METHODS
The patients were recruited at the Department of Pulmonary Medicine, and the study was conducted at the Department of Endocrinology, University of Lund, Malmö University Hospital, Malmö, Sweden.


METHODS
Sixty-two patients with documented sarcoidosis (30 females, 32 males, 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/range 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 patients with associated autoimmunity compared with those with isolated sarcoidosis (P = 0.0328). A significant association was seen between ACE gene polymorphism (II, ID, DD genotypes) and S-ACE levels in both patients and controls according to the order II < ID < DD. The observed genotype frequency distributions in the different study groups agreed the Hardy-Weinberg equilibrium without significant differences between the patients and the controls. Within the group with autoimmune manifestations the DD genotype was significantly over-represented in X-ray stage III compared to the other X-ray stages (P = 0.0181) and a significant increase in the DD genotype in X-ray stage III (P = 0.035) in the group with autoimmune manifestations compared to isolated sarcoidosis was detected.


CONCLUSIONS
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-ACE levels were significantly higher in sarcoidosis patients with autoimmune manifestations. The frequency of the DD genotype was significantly increased in patients with autoimmune manifestations and major granuloma mass (X-ray stage III). The ACE D allele in its homozygous form may confer susceptibility for autoimmune manifestations in sarcoidosis, possibly via the high levels of S-ACE it encodes.
Papadopoulos
K I
KI
Department of Endocrinology, University of Lund, Malmö University Hospital, Malmö, Sweden. endocrine@otenet.gr
Melander
O
O
Orho-Melander
M
M
Groop
L C
LC
Carlsson
M
M
Hallengren
B
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015551:Autoimmunity / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000737:chemistry; D004251:DNA Transposable Elements / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012507:Sarcoidosis / Q000235:genetics* / Q000276:immunology*
D004251:DNA Transposable Elements; D004247:DNA; D007703:Peptidyl-Dipeptidase A