Objective. Takayasu arteritis (TAK) is a systemic vasculitis affecting large arteries and large branches of the aorta. Ulcerative colitis (UC) is a prevalent autoimmune colitis. Since TAK and UC share HLA-B*52:01 and IL12B as genetic determinants, and since there are case reports of the co-occurrence of these diseases, we hypothesized that UC is a common complication of TAK. We undertook this study to perform a large-scale analysis of TAK, both to evaluate the prevalence of concurrent cases of TAK and UC and to identify and estimate susceptibility genes shared between the 2 diseases.Methods. We analyzed a total of 470 consecutive patients with TAK from 14 institutions. We characterized patients with TAK and UC by analyzing clinical manifestations and genetic components. Genetic overlapping of TAK and UC was evaluated with the use of UC susceptibility single-nucleotide polymorphisms by comparing risk directions and effect sizes between susceptibility to the 2 diseases.Results. Thirty of 470 patients with TAK had UC (6.4% [95% confidence interval 4.3-9.0]). This percentage was strikingly higher than that expected from the prevalence of UC in Japan. Patients with TAK complicated with UC developed TAK at an earlier stage of life (P 5 0.0070) and showed significant enrichment of HLA-B*52:01 compared to TAK patients without UC (P 5 1.0 3 10 25 ) (odds ratio 12.14 [95% confidence interval 2.96-107.23]). The 110 non-HLA markers of susceptibility to UC significantly displayed common risk directions with susceptibility to TAK (P 5 0.0054) and showed significant departure of permutation P values from expected P values (P < 1.0 3 10 210 ).Conclusion. UC is a major complication of TAK. These 2 diseases share a significant proportion of their genetic background, and HLA-B*52:01 may play a central role in their co-occurrence.

Takayasu arteritis (TAK) is a systemic vasculitis with severe complications that affects the aorta and its large branches. HLA-B*52 is an established susceptibility locus to TAK. To date, there are still only a limited number of reports concerning non-HLA susceptibility loci to TAK. We conducted a genome-wide association study (GWAS) and a follow-up study in a total of 633 TAK cases and 5,928 controls. A total of 510,879 SNPs were genotyped, and 5,875,450 SNPs were imputed together with HLA-B*52. Functional annotation of significant loci, enhancer enrichment, and pathway analyses were conducted. We identified four unreported significant loci, namely rs2322599, rs103294, rs17133698, and rs1713450, in PTK2B, LILRA3/LILRB2, DUSP22, and KLHL33, respectively. Two additional significant loci unreported in non-European GWAS were identified, namely HSPA6/FCGR3A and chr21q.22. We found that a single variant associated with the expression of MICB, a ligand for natural killer (NK) cell receptor, could explain the entire association with the HLA-B region. Rs2322599 is strongly associated with the expression of PTK2B. Rs103294 risk allele in LILRA3/LILRB2 is known to be a tagging SNP for the deletion of LILRA3, a soluble receptor of HLA class I molecules. We found a significant epistasis effect between HLA-B*52 and rs103294 (P = 1.2 × 10−3). Enhancer enrichment analysis and pathway analysis suggested the involvement of NK cells (P = 8.8 × 10−5, enhancer enrichment). In conclusion, four unreported TAK susceptibility loci and an epistasis effect between LILRA3 and HLA-B*52 were identified. HLA and non-HLA regions suggested a critical role for NK cells in TAK.

Characteristics of peripheral arterial disease (PAD) are the occlusion or stenosis of multiple vessel sites caused mainly by atherosclerosis and chronic lower limb ischemia. To identify PAD susceptible loci, we conducted a genome-wide association study (GWAS) with 785 cases and 3,383 controls in a Japanese population using 431,666 single nucleotide polymorphisms (SNP). After staged analyses including a total of 3,164 cases and 20,134 controls, we identified 3 novel PAD susceptibility loci at IPO5/RAP2A, EDNRA and HDAC9 with genome wide significance (combined P = 6.8 x 10−14, 5.3 x 10−9 and 8.8 x 10−8, respectively). Fine-mapping at the IPO5/RAP2A locus revealed that rs9584669 conferred risk of PAD. Luciferase assay showed that the risk allele at this locus reduced expression levels of IPO5. To our knowledge, these are the first genetic risk factors for PAD.

BackgroundWhich graft material is the optimal graft material for the treatment of infected aortic aneurysms and aortic graft infections is still a matter of controversy. Orthotopic aortic reconstruction with intraoperatively prepared xenopericardial roll grafts without omentopexy was performed as the “initial” operation to treat aortic infection or as a “rescue” operation to treat graft infection. Mid-term outcomes were evaluated.MethodsBetween 2009 and 2013, orthotopic xenopericardial roll graft replacement was performed to treat eight patients (male/female: 6/2; mean age: 69.5 [55–80] yr). Graft material: equine/bovine pericardium: 2/6; type of operation: initial 4/rescue 4; omentopexy 0. Additional operation: esophagectomy 2. Mean follow-up period: 2.6 ± 1.6 (1.1–5.1) years.ResultsReplacement: ascending 3, arch 1 (reconstruction of neck vessels with small xenopericardial roll grafts), descending 3, and thoracoabdominal 1. Pathogens: MRSA 2, MSSA 1, Candida 1, E. coli 1, oral bacillus 1, and culture negative 2. Postoperative local recurrence of infection: 0. Graft-related complications: stenosis 0, calcification 0, non-infectious pseudoaneurysm of anastomosis 2 (surgical repair: 1/TEVAR 1). In-hospital mortality: 2 (MOF: initial 1/rescue 1); Survival rate exclusive of in-hospital deaths (~3 y): 100 %, but one patient died of lung cancer (3.6 yr).ConclusionsBecause xenopericardial roll grafts are not composed of synthetic material, the replacement procedure is simpler and less invasive than the standard procedure. Based on the favorable results obtained, this procedure may have the possibility to serve as an option for the treatment of aortic infections and aortic graft infections not only as a “rescue” treatment but as an “initial” treatment as well.Electronic supplementary materialThe online version of this article (doi:10.1186/s13019-015-0343-5) contains supplementary material, which is available to authorized users.