Angiotensin Converting Enzyme Gene Insertion-Deletion Polymorphism Is Associated with Juvenile Rheumatoid Arthritis

KHALED ALSAEID, M. ZAFARYAB HAIDER, and ELIA M. AYOUB

ABSTRACT.

Objective. To investigate the incidence of angiotensin converting enzyme (ACE) gene insertion-deletion (I/D) polymorphism genotypes in children with juvenile rheumatoid arthritis (JRA), a heterogenous chronic disease with autoimmune pathology. ACE gene I/D polymorphism influences the plasma and tissue levels of ACE and has an involvement in inflammatory mechanisms.

Methods. The incidence of ACE gene I/D polymorphism genotypes was determined in 82 children with JRA from Kuwait and compared to that in 48 ethnically matched healthy controls using polymerase chain reaction.

Results. A considerably higher incidence of II genotype was observed in the JRA patients compared to controls (p < 0.003). In contrast, no statistically significant difference was detected in the incidence of DD and ID genotypes in JRA patients and controls (p = 0.276 and 0.460, respectively). The incidence of ACE gene polymorphism genotypes was also studied in clinical subclasses of JRA patients and controls. There was no significant difference in the incidence of DD and ID genotypes in either of the 3 JRA subclasses (oligoarticular, polyarticular, and systemic) when compared to controls. However, the incidence of II genotype was found to be significantly higher in all the 3 JRA subclasses compared to controls. The strongest association between II genotype and JRA subclasses was detected in systemic JRA, followed by oligoarticular and polyarticular JRA. This was also reflected in a higher prevalence of I- allele in the systemic JRA cases (13/26, 50%) compared to the D-allele (11/26, 42%). In contrast, D-allele of the ACE gene was more prevalent in oligoarticular and polyarticular JRA cases, than the I-allele (61% and 58%, respectively).

Conclusion. Our data suggest a significant association of the I-allele of the ACE gene I/D polymorphism with the 3 clinical subclasses of JRA in children, and the highest association was observed in systemic JRA cases. (J Rheumatol 2003;30:2705-9)

Key Indexing Terms:

ANGIOTENSIN CONVERTING ENZYME
GENOTYPE
POLYMORPHISM
JUVENILE RHEUMATOID ARTHRITIS
POLYMERASE CHAIN REACTION

---

From the Departments of Pediatrics, Faculty of Medicine, Kuwait University and Mubarak Al-Kabeer Hospital, Safat, Kuwait, and the University of Florida, Gainesville, Florida, USA.

Supported by funds provided by the Kuwait University.

K. Alsaeid, MD, FAAP, Associate Professor, Kuwait University and Mubarak Al-Kabeer Hospital; M.Z. Haider, PhD, Associate Professor, Kuwait University; E.M. Ayoub MD, FAAP, Professor, University of Florida.

Address reprint requests to Dr. M.Z. Haider, Kuwait University Faculty of Medicine, Pediatrics Department, PO Box 24923, Safat 13110, Kuwait. E-mail: haider@hsc.kuniv.edu.kw

Submitted November 1, 2002; revision accepted May 5, 2003.

---