The role of human leukocyte antigen genes in the formation of abdominal aortic aneurysms
Received 21 July 2006; accepted 19 September 2006.
Background
Increasing evidence suggests an autoimmune component to abdominal aortic aneurysm (AAA) formation. This study was conducted to determine if a difference exists in human leukocyte antigen (HLA) allele distribution between patients with AAA and population controls, and between patients with small and large AAA.
Methods
Patients with known AAA attending the vascular unit were consented for recruitment. HLA-A, HLA-B and HLA-DR was determined by polymerase chain reaction and sequence-specific oligonucleotide probes. The distribution of these alleles in the Northern Ireland general population was obtained from the histocompatability and immunogenetics database. The χ2 test was used for statistical analysis with Bonferroni correction.
Results
A total of 241 AAA patients were recruited, with a wide range of aneurysm size. In class I, the most frequent allele families were HLA-A*02 and *01 and HLA-B*07, *08, and *44. In class II, HLA-DRB1*03, *04, *07, and *15 were the most frequent. HLA-A*11 was lower in AAA cases (10.4% vs 15.0%; P = .08), whereas HLA-B*08 was lower in the controls (29.8% vs 36.5%; P = .05) and HLA-DRB1*11 was lower in cases (4.2% vs 8.1%; P = .05). After Bonferroni correction, however, the proportion of allele families was not significantly different in AAA patients compared with the proportion seen in controls. HLA-DRB1*11 and *14 had a lower prevalence in large AAAs (0.9% vs 6.7% [P = .05]; 0.0% vs 5.9% [P = .03]). HLA-A*68 was also lower in large AAA (1.9% vs 11.9%; P = .0075). After Bonferroni correction, however, no difference was demonstrated between small and large aneurysms.
Conclusion
This study provides more definitive results on this important subject and has failed to demonstrate the risk association between AAA and these alleles as reported by others. Therefore, the role of these particular genes and the autoimmune component in AAA etiology does not appear to be as crucial as previously proposed.
Clinical Relevance
The high mortality of patients who sustain ruptured abdominal aortic aneurysms compared with elective repair justifies surgery in medically suitable patients with a large aneurysm. Control of the growth of smaller aneurysms may offer an alternative to surgery, however. This is dependent on better elucidation of underlying causal factors, including the role of genetic predisposition and autoimmunity. This study was designed to assess the contribution of human leukocyte antigen genes, which could thereby lay the foundation for future preventive therapy of this important disease.
aVascular and Endovascular Surgery Centre, Belfast City Hospital, Belfast, United Kingdom
bHistocompatability and Immunogenetics Laboratory, Belfast City Hospital, Belfast, United Kingdom.
Reprint requests: Mr S. Badger, Vascular Research Fellow, Belfast City Hospital, Lisburn Rd, Belfast BT9 7AB, UK.
ABSTRACT