Takayasu arteritis and ulcerative colitis: high rate of co-occurrence and genetic overlap.
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 = 0.0070) and showed significant enrichment of HLA-B*52:01 compared to TAK patients without UC (P = 1.0 × 10(-5) ) (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 = 0.0054) and showed significant departure of permutation P values from expected P values (P < 1.0 × 10(-10) ).


CONCLUSIONS
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.
Kyoto University Graduate School of Medicine, Kyoto, Japan.
Chikashi
C
Terao
University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Takayoshi
T
Matsumura
Kyoto University Graduate School of Medicine, Kyoto, Japan.
Hajime
H
Yoshifuji
Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Yohei
Y
Kirino
Tokyo Medical and Dental University, Tokyo, Japan.
Yasuhiro
Y
Maejima
Osaka University Graduate School of Medicine, Osaka, Japan.
Yoshikazu
Y
Nakaoka
Kyoto University Graduate School of Medicine, Kyoto, Japan.
Meiko
M
Takahashi
University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Eisuke
E
Amiya
Tokyo Medical and Dental University, Tokyo, Japan.
Natsuko
N
Tamura
Kyoto University Graduate School of Medicine, Kyoto, Japan.
Toshiki
T
Nakajima
Nagasaki University School of Health Sciences, Nagasaki, Japan.
Tomoki
T
Origuchi
Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Tetsuya
T
Horita
University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Mitsuru
M
Matsukura
University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Yuta
Y
Kochi
Ehime University Graduate School of Medicine, Ehime, Japan.
Akiyoshi
A
Ogimoto
Sapporo Medical University, Sapporo, Japan.
Motohisa
M
Yamamoto
Sapporo Medical University, Sapporo, Japan.
Hiroki
H
Takahashi
University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan.
Shingo
S
Nakayamada
University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan.
Kazuyoshi
K
Saito
Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Yoko
Y
Wada
Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Ichiei
I
Narita
Tokyo Women's Medical University, Tokyo, Japan.
Yasushi
Y
Kawaguchi
Tokyo Women's Medical University, Tokyo, Japan.
Hisashi
H
Yamanaka
Kyoto University Graduate School of Medicine, Kyoto, Japan.
Koichiro
K
Ohmura
Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Tatsuya
T
Atsumi
Kawasaki Medical School, Kurashiki, Japan.
Kazuo
K
Tanemoto
University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Tetsuro
T
Miyata
Keio University School of Medicine, Tokyo, Japan.
Masataka
M
Kuwana
University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Issei
I
Komuro
Kyoto University Graduate School of Medicine, Kyoto, Japan.
Yasuharu
Y
Tabara
Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Atsuhisa
A
Ueda
Tokyo Medical and Dental University, Tokyo, Japan.
Mitsuaki
M
Isobe
Kyoto University Graduate School of Medicine, Kyoto, Japan.
Tsuneyo
T
Mimori
Kyoto University Graduate School of Medicine, Kyoto, Japan.
Fumihiko
F
Matsuda
D000328:Adult; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000235:genetics*; D015897:Comorbidity; D005260:Female; D020022:Genetic Predisposition to Disease; D059950:HLA-B52 Antigen / Q000235:genetics*; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D013625:Takayasu Arteritis / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
C501279:HLA-B*52:01 antigen; D059950:HLA-B52 Antigen; C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40