DELETION POLYMORPHISM IN THE ANGIOTENSIN-I CONVERTING-ENZYME (ACE) GENE AS A GENETIC RISK FACTOR FOR SARCOIDOSIS

Background - Genetic control of serum angiotensin I converting enzyme (SAGE) levels has been suggested. A study was undertaken to elucidate the role of this polymorphism in sarcoidosis. Methods - Three hundred and forty one unrelated healthy controls and 103 consecutive patients with sarcoidosis participated in the study. SAGE levels and an inserti on/deletion (I/D) polymorphism in intron 16 of the ACE gene were studi ed in each subject and new reference intervals for SAGE activity for e ach genotype were determined. The difference in genotype and allele fr equencies between controls and patients was analysed and odds ratios w ere calculated to estimate the relative risk. Results - A significant association was seen between ACE gene polymorphism and SAGE levels in both patients and controls. The new reference intervals for each genot ype discriminated abnormal SAGE levels in patients more accurately, es pecially those with genotype II. In women the frequencies of allele I were 0.68 (allele D 0.32) in controls and 0.58 (allele D 0.42) in pati ents, and the difference between the two female groups was significant (p < 0.05). Thus, an excess of genotype ID or DD was observed in fema le patients (odds ratio 2.18; 95% confidence interval 1.18 to 4.01; p = 0.01). Conclusions - These findings suggest that ACE gene polymorphi sm is associated with SAGE levels in both patients with sarcoidosis an d controls. ACE gene polymorphism should be further evaluated as a can didate marker for an increased risk of sarcoidosis.