Significant Association of Insertion/Deletion Polymorphism of the Angiotensin-Converting Enzyme Gene with Rheumatoid Arthritis

SUKHBIR S. UPPAL, MOHAMMAD Z. HAIDER, SAWSAN J. HAYAT, MINI ABRAHAM, JALAJA SUKUMARAN, and GURSEV S. DHAUNSI

ABSTRACT.

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.

Conclusion. Our study found an association between ACE deletion polymorphism and RA. (First Release Nov 1 2007; J Rheumatol 2007;34:2395-9)

Key Indexing Terms:

ANGIOTENSIN-CONVERTING ENZYME \
KUWAIT
RHEUMATOID ARTHRITIS
INSERTION/DELETION POLYMORPHISM

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From the Departments of Medicine and Pediatrics, Faculty of Medicine, Kuwait University; and Department of Medicine, Mubarak Al-Kabeer Hospital, Kuwait.

S.S. Uppal, MBBS, MD, FICP, FRCP Edin, Associate Professor, Consultant Rheumatologist, Departments of Medicine, Kuwait University and Mubarak Al-Kabeer Hospital; M.Z. Haider, PhD, Professor; J. Sukumaran, MSc, Scientific Assistant; G.S. Dhaunsi, PhD, Associate Professor, Department of Pediatrics; M. Abraham, MBBS, Laboratory Physician, Department of Medicine, Kuwait University; S.J. Hayat, BMBCh, Registrar in Medicine, Department of Medicine, Mubarak Al-Kabeer Hospital.

Address reprint requests to Dr. S.S. Uppal, Department of Medicine, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait. E-mail: uppalss@hsc.edu.kw

Accepted for publication July 5, 2007.

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