Human leukocyte antigen class II immune response genes, female gender, and cigarette smoking as risk and modulating factors in abdominal aortic aneurysms.
OBJECTIVE
Aortic inflammation and the genes that regulate the immune response play an important role in abdominal aortic aneurysm pathogenesis. However, the modulating effects of such genetic and other environmental factors on the severity on aneurysm inflammation is not known. The objective of this study was to determine the influence of the human leukocyte antigen (HLA) class II genes, gender, and environmental factors on degree of abdominal aortic aneurysm tissue inflammation.


METHODS
Aneurysm specimens were obtained at the time of operation from 96 consecutive patients who underwent abdominal aortic aneurysm repair and were graded for degree of histologic inflammation. Multivariate analysis was used to determine the association of genetic and environmental factors with degree of inflammation and to determine the HLA-associated disease risk for aneurysm.


RESULTS
Active cigarette smoking and female gender were independently associated with high-grade tissue inflammation identified histologically (odds ratio [OR], confidence interval [CI]: 5.6, 1.6 to 19.3; and 6.0, 1.4 to 26.2, respectively), and a specific HLA allele (DR B1(*)01) was inversely associated with inflammation (OR, CI: 0.2, 0.04 to 0.7). Overall, the HLA-DR B1(*)02 and B1(*)04 alleles were significantly associated with disease risk, more than doubling risk for abdominal aortic aneurysm (OR, CI: 2.5, 1.4 to 4.3; and 2.1, 1.2 to 3.7, respectively).


CONCLUSIONS
Active cigarette smoking and female gender are significant disease-modulating factors associated with increased abdominal aortic aneurysm inflammation. In addition, the HLA class II immune response genes possess both disease modulating and disease risk properties, which may be useful in early aneurysm detection and surveillance.
Rasmussen
Todd E
TE
Department of Surgery, Uniformed Services University of Health Sciences, Malcolm Grow USAF Medical Center, Andrews Air Force Base, MD 20762, USA.
Hallett
John W
JW
Tazelaar
Henry D
HD
Miller
Virginia M
VM
Schulte
Stephanie
S
O'Fallon
W Michael
WM
Weyand
Cornelia M
CM
D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology* / Q000235:genetics* / Q000276:immunology; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics* / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics* / Q000276:immunology
D006680:HLA Antigens