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Lack of association between angiotensin converting enzyme gene polymorphism and Korean Behçet’s disease
  1. H K Chang1,
  2. J U Kim2,
  3. S S Lee3,
  4. D H Yoo4
  1. 1Department of Internal Medicine, Dankook University, Cheonan, South Korea
  2. 2Department of Laboratory Medicine, Ulsan University, Kangnung, South Korea
  3. 3Department of Internal Medicine, Chonnam National University Medical School, Gwangju, South Korea
  4. 4Department of Internal Medicine, The Hospital for Rheumatic Diseases, Hanyang University, Seoul, South Korea
  1. Correspondence to:
    Dr H K Chang
    Division of Rheumatology, Department of Internal Medicine, Dankook University, 16-5 Anseo-Dong, Cheonan, Chungcheongnamdo, 330-715, South Korea;

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The histological hallmark of Behçet’s disease (BD) is a vasculitis, and endothelial dysfunction has a role in the development of the vascular lesions in BD.1,2 Angiotensin converting enzyme (ACE) plays a part in the renin-angiotensin and kallikrein-kininogen systems by producing angiotensin II from angiotensin I and by inactivating bradykinin. The ACE gene is located on the long arm of chromosome 17, and insertion and deletion (I/D) polymorphism of this gene is strongly related to the levels of circulating ACE: the serum levels of ACE in the DD genotype, homozygote for the deletion allele, are about twice as high as those in the II genotype, homozygote for the insertion allele.3 In addition, the DD genotype is associated with endothelial dysfunction, as the stimulated endothelial or donated nitric oxide response is blunted.4 Moreover, angiotensin II may participate in the vascular pathogenesis of several diseases through vascular smooth muscle cell contraction and proliferation, monocyte adhesion, and platelet aggregation. However, to our knowledge, there have been no studies on the relationship between the ACE gene and BD. Thus, we studied the potential association between ACE I/D gene polymorphism and Korean BD.


The study group included 70 patients with BD (27 men and 43 women; mean (SD) age 38.1 (7.8)) fulfilling the international study group criteria5 and 106 healthy controls (37 men and 69 women; mean (SD) age 37 (11.5)). All the subjects were ethnically homogenous Koreans, unrelated to each other. The cumulative history of severe manifestations was investigated during the disease course, as described in our previous study.6 Informed consent was obtained from all the subjects.

ACE I/D polymorphism was determined by polymerase chain reaction genotyping.7 The statistical significance was evaluated using χ2 test, t test, or one way analysis of variance test. Values of p<0.05 were considered significant, and these were corrected by multiplying the values by the number of alleles in certain cases.

Table 1 shows that the distribution of genotypes and alleles of the ACE gene did not differ significantly between patients with BD and controls (p>0.05), and it was in Hardy-Weinberg equilibrium. In a comparison of clinical variables including sex, clinical manifestations, severe manifestations, and positivity of HLA-B51, no significant associations were found in the frequencies of genotypes and alleles between patients with BD with and without each criterion (all p>0.05). Although the D allele frequency was significantly higher in male patients than in female patients, the significance was lost when multiplying by the number of alleles (p = 0.033, pcorr = 0.066).

Table 1

The distribution of angiotensin converting enzyme genotypes and alleles in the patients with BD and controls

The mean (SD) ages at onset of patients with BD in each genotype were 33.3 (8.3) (DD), 33.3 (8.0) (ID), and 32.5 (8.2) years (II), and no differences were seen between groups (p>0.05). In a comparison of patients with BD with and without each genotype (DD, ID, II), frequencies of clinical variables (sex, clinical manifestations, severe manifestations, positivity of HLA-B51, mean age at onset) did not differ significantly (all p>0.05) (data not shown).


Genetic susceptibility to BD is affected by multiple genes, such as major histocompatibility complex (MHC) and non-MHC genes. Endothelial nitric oxide synthase (eNOS) gene polymorphisms are noted to be associated with the pathogenesis of various vascular diseases, including coronary artery disease (CAD), myocardial infarction (MI), hypertension, and renal diseases. Recently, we reported that Glu298Asp polymorphism of the eNOS gene was another susceptibility gene for Korean BD and other rheumatic diseases with vasculitis.8

ACE gene polymorphism is also reported to be a risk factor for CAD, MI, hypertension, and renal diseases. Furthermore, the DD ACE genotype is associated with endothelial dysfunction, which is believed to have an important role in the development of the vascular lesions in BD.2,4 On the other hand, associations between the ACE gene and non-Behçet’s rheumatic diseases with vascular involvement have been inconsistently reported.9,10 We therefore considered that the ACE gene might be another candidate gene for BD. However, we could not detect any significant correlation between BD and ACE gene polymorphism. Because of the well known regional differences in the disease expression of BD, further studies in other ethnic populations will be required.


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  • This study was supported by the research fund of Dankook University in 2003.

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