Negative genetic risk factor for abdominal aortic aneurysm: HLA-DQ3, a Japanese study
Article Outline
To the Editors:
Abdominal aortic aneurysms (AAAs) may be related to specific HLA alleles.1, 2 We have reported that HLA-DR2(15) is a positive risk factor for nonspecific infrarenal AAAs in Japan.3 HLA class II antigens are further divided into DR and DQ antigens, which are expressed independently on the antigen presenting cells. Some DQ alleles are reported to be associated with autoimmune diseases, such as Hashimoto’s thyroiditis.4 This study was performed to determine whether specific HLA DQ alleles are associated with AAA.
METHOD
Peripheral blood samples were obtained from 36 patients with AAAs and from 39 volunteers, most of whom were among the subjects (all Japanese) on whom we have previously reported an association with HLA-DR2(15). The age, sex, and associated medical problems of the two groups were similar (data not shown). DQ antigen typing was performed at the Mitsubishi Biochemical Laboratory (MBC, Tokyo, Japan) with a serologic technique.5 The homozygosity was identified if only one antigen was identified from an individual. The typing tests were repeated to confirm that the results were not simple serologic reagent error. The frequency of antigens of HLA-DQ alleles were compared with the χ2 test.
RESULTS
The AAA group consisted of 30 men and six women, with an age distribution from 47 to 85 years (mean, 71.8 years). Three AAAs were ruptured, and the others were intact infrarenal AAAs with diameters of 4 cm to 10.0 cm (mean, 5.7 cm). The distributions of HLA-DQ are shown in Table I.
Table I. Frequency of HLA-DQ alleles in patients with abdominal aortic aneurysms and control subjects
| HLA DR antigen | AAA group | Control group | P value | |
|---|---|---|---|---|
| No. of antigens (no. of patients) | No. of antigens (no. of patients) | |||
| DQ1 | 41 (30) | 34 (28) | .102 | NS |
| DQ2 | 3 (2) | 0 (0) | .069 | NS |
| DQ3 | 16 (16) | 32 (27) | .014 | <.02 |
| DQ4 | 12 (11) | 12 (11) | .999 | NS |
| Total | 72 (36) | 78 (39) | ||
DISCUSSION
These study results suggested that HLA-DQ3 antigen appeared to have a protective effect in relation to AAA. However, the relation of DQ3 and DR2(15) remained unknown. Suppressive effects of certain DQ alleles have been reported in other autoimmune conditions, like Hashimoto’s thyroiditis and insulin-dependent diabetes mellitus.6
When DR status is included in the analysis of these groups of patients with AAA and control subjects, the data further suggest that DR2(15) promotes AAA disease and DQ3 protects. If DR2(15) positive and DQ3 negative are considered to be the high-risk serotypes, then 89% (32 of 36) of the patients with AAA had one of these features as compared with 41% (16 of 39) of the control subjects (P < .0001).
24/8/101467
References
- . Hypothesis: a genetic basis for autoimmune manifestations in the abdominal aortic aneurysm (AAA). N Y Acad Sci. 1996;800:208–217
- Genetic risk factors in inflammatory abdominal aortic aneurysms: polymorphic residue 70 in the HLA-DR B1 gene as a key genetic element. J Vasc Surg. 1997;25:356–364
- Genetic risk factor for abdominal aortic aneurysm: HLA-DR2(15), a Japanese study. J Vasc Surg. 1998;27:500–503
- General organization and overview of the disease component. In: Tsuji K, Aizawa M, Sasazuki T editor. HLA 1991: proceedings of the eleventh international histocompatibility workshop and conference. Oxford: Oxford University Press; 1992;p. 693–700
- . Microdroplet testing for HLA-A, -B, -C, and -D antigens. Am J Clin Pathol. 1978;69:103–120
- . Functional domains on HLA-DR molecules: implications for the linkage of HLA-DR genes to different autoimmune disease. Clin Immunol Immunopathol. 1994;70:91–98
PII: S0741-5214(99)70025-X
© 1999 Mosby, Inc. All rights reserved.
