Negative genetic risk factor for abdominal aortic aneurysm: HLA-DQ3, a Japanese study

Abstract

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. METHODPeripheral 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 χ 2 test. RESULTSThe 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. The frequency of HLA-DQ3 antigen was significantly decreased in the AAA group (22.2% in AAAs and 41.0% in controls), with a P value of less than .02. Homozygous DQ3 was observed in five control subjects but was not observed in relation to the AAA group. DISCUSSIONThese 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).

The Candidate Gene Approach to Susceptibility for Abdominal Aortic Aneurysm

“…We were using “degenerate” primers to try to clone a cDNA for aneurysm‐associated‐antigenic protein‐40 kDa (AAAP‐40), and among many uninteresting cDNA sequences that were determined, there was a cDNA for FTL from fibroblasts cultured from a AAA specimen. This finding preempted our attention because there were three substitutions, two of which changed codons 18 . Further studies have been done on genomic DNA from our collection of AAA specimens.…”

Chronic Inflammation, Immune Response, and Infection in Abdominal Aortic Aneurysms

“…For instance, specific alleles of HLA-DR2, but not HLA-DQ3 are frequently observed in AAA, similar to what is reported in rheumatoid arthritis and multiple sclerosis. [60][61][62][63][64][65][66][67][68][69][70] Rasmussen et al showed that the B1(*)02 and B1(*)04 alleles in HLA were associated with more than a doubled risk of AAA, and that the degree of inflammation quantified histologically was associated with these tissue types. These results suggest the HLA class II immune response genes possess both diseasemodulation and disease-risk properties, and thus that some kind of a genetic susceptibility to aortic inflammation exists.…”

Circulatory CD4-Positive T-Lymphocyte Imbalance Mediated by Homocysteine-Induced AIM2 and NLRP1 Inflammasome Upregulation and Activation Is Associated with Human Abdominal Aortic Aneurysm

“…Moreover, Russell’s corpuscle, which is commonly seen in autoimmune diseases such as Hashimoto’s thyroiditis, is also common in AAA [31]. A characteristic of autoimmune disease is genetic susceptibility, and as in rheumatoid arthritis and multiple sclerosis, AAA patients frequently have human leukocyte antigen (HLA)-DR2 mutation [32]. Regarding the origin of abdominal aortic artery autoimmunity, repeated infection by a specific pathogen might be the reason thereof.…”