Significant association of insertion/deletion polymorphism of the angiotensin-converting enzyme gene with rheumatoid arthritis.
OBJECTIVE
Only 30% of the genetic contribution to rheumatoid arthritis (RA) can be attributed to HLA genes, and other non-HLA genes may play a role in RA susceptibility. Angiotensin-converting enzyme (ACE) has been reported to be involved in pathogenesis of RA, and high levels of ACE have been documented in RA synovial fluid and pleural effusions. Since plasma and tissue levels of ACE are determined at the transcriptional level, we test the hypothesis that the genotype of ACE in RA patients may be a determining factor in pathogenesis.


METHODS
Sixty patients with RA were recruited and clinically characterized according to disease duration, disease severity, disease activity, and American College of Rheumatology functional classes. ACE gene I/D polymorphism genotypes were determined in patients and healthy controls, using polymerase chain reaction.


RESULTS
We found a significant overrepresentation of the DD genotype and the D allele in patients with RA; and we found that men with RA exhibited a higher frequency of the DD genotype and D allele compared to male controls. By logistic regression analysis the DD genotype confers a relative risk for development of RA of 3.


CONCLUSIONS
Our study found an association between ACE deletion polymorphism and RA.
Uppal
Sukhbir S
SS
Department of Medicine, Faculty of Medicine, Kuwait University, Kuwait. uppalss@hsc.edu.kw
Haider
Mohammad Z
MZ
Hayat
Sawsan J
SJ
Abraham
Mini
M
Sukumaran
Jalaja
J
Dhaunsi
Gursev S
GS
D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D007703:Peptidyl-Dipeptidase A