PMID- 16386648 OWN - NLM STAT- MEDLINE DCOM- 20060922 LR - 20111117 IS - 0198-8859 (Print) IS - 0198-8859 (Linking) VI - 66 IP - 10 DP - 2005 Oct TI - DRB1-TNF-alpha-TNF-beta haplotype is strongly associated with severe aortoiliac occlusive disease, a clinical form of atherosclerosis. PG - 1062-7 AB - Severe aortoiliac occlusive disease (AOD) is a clinical manifestation of peripheral arteriosclerosis. Atherosclerosis has been associated with some human leukocyte antigen (HLA)-DRB1 alleles, stressing its relationship with autoimmune or inflammatory disorders. Additionally, in rheumatoid arthritis patients, the DRB1*0404 allele is specifically associated with endothelial dysfunction. Our objective was to assess the role of class II HLA alleles in the susceptibility to AOD; a combined study of the nearby tumor necrosis factor (TNF) locus was also performed. We included 104 AOD patients and 504 healthy controls from Madrid. DRB1 typing and DRB1*04 subtyping was done by polymerase chain reaction amplification followed by hybridization with specific oligonucleotides. TNF-alpha and TNF-beta microsatellites were studied by polymerase chain reaction and capillary electrophoresis. None of the markers was associated with AOD, although a trend was observed for DRB1*0404 (OR = 2.18; p = 0.05). However, among DRB1*0404 individuals, the TNFa11-b4 pair was present more frequently in patients than in controls (OR = 16.0; p = 0.007). The combined appearance of TNFa11-b4 and DRB1*0404 was much more frequent in patients than in controls (OR = 5.92; p = 0.0013), a result enhanced by haplotypic estimates (OR = 10.0; p = 0.00017). Our results show that the HLA region modulates the predisposition to AOD. More specifically, they suggest that an extended haplotype encompassing DRB1*0404 and TNFa11-b4 carries a genetic factor conferring susceptibility to AOD. FAU - Mas, Alfonso AU - Mas A AD - Department of Immunology Hospital Clinico San Carlos, Madrid, Spain. FAU - Blanco, E AU - Blanco E FAU - Monux, G AU - Monux G FAU - Urcelay, E AU - Urcelay E FAU - Serrano, F J AU - Serrano FJ FAU - de la Concha, E G AU - de la Concha EG FAU - Martinez, A AU - Martinez A LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20051102 PL - United States TA - Hum Immunol JT - Human immunology JID - 8010936 RN - 0 (HLA DRB1*04:04 antigen) RN - 0 (HLA-DR Antigens) RN - 0 (HLA-DRB1 Chains) RN - 0 (Lymphotoxin-alpha) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Alleles MH - Arterial Occlusive Diseases/*genetics MH - Atherosclerosis/*genetics MH - Confidence Intervals MH - Female MH - Gene Frequency MH - Genetic Predisposition to Disease MH - HLA-DR Antigens/*genetics MH - HLA-DRB1 Chains MH - Haplotypes MH - Humans MH - Lymphotoxin-alpha/*genetics MH - Male MH - Middle Aged MH - Odds Ratio MH - Polymorphism, Genetic MH - Tumor Necrosis Factor-alpha/*genetics EDAT- 2006/01/03 09:00 MHDA- 2006/09/23 09:00 CRDT- 2006/01/03 09:00 PHST- 2005/08/10 00:00 [received] PHST- 2005/09/29 00:00 [accepted] PHST- 2006/01/03 09:00 [pubmed] PHST- 2006/09/23 09:00 [medline] PHST- 2006/01/03 09:00 [entrez] AID - S0198-8859(05)00425-8 [pii] AID - 10.1016/j.humimm.2005.10.001 [doi] PST - ppublish SO - Hum Immunol. 2005 Oct;66(10):1062-7. doi: 10.1016/j.humimm.2005.10.001. Epub 2005 Nov 2.