Takayasu Arteritis

<p>Hirsch et al. (1964) observed Japanese sisters with aortic arch syndrome. This common disease in Japanese is not strikingly familial. The racial concentration of cases is not necessarily genetic. The disease is relatively frequent throughout the Orient, for example, in India among Caucasoid people of that country. Several studies suggest an autoimmune basis. A modest familial aggregation may have the same basis as that observed in other types of possible autoimmune disease, such as Hashimoto struma (140300). Hermann and Pluhor (1964) observed affected European sisters. Numano et al. (1978) reported the disorder in Japanese monozygotic twin sisters whose parents were healthy but first cousins. They reviewed several other reports of familial occurrence including 3 mother-daughter pairs, 3 sister pairs, and 2 brother-sister pairs. Numano et al. (1979) pointed out the high frequency in South America as well as in Asia. In 10 affected women in North America (7 white, 2 Korean, 1 racially mixed (white-black)), Volkman et al. (1982) found an association with MB3 and DR4. Yoshida et al. (1993) confirmed an increased frequency of HLA-B52, as reported by Isohisa et al. (1978). Furthermore, they showed that the disease-associated HLA-B alleles share an epitope composed of glu63 and ser67. p><p>Matsuyama et al. (2003) measured circulating levels of the matrix metalloproteinases 2 (MMP2; 120360), 3 (MMP3; 185250), and 9 (MMP9; 120361) in 25 patients with Takayasu arteritis and 20 age- and sex-matched healthy controls. Levels of all 3 metalloproteinases were higher in patients with active disease than in controls (p less than 0.0001 for each), and MMP2 levels remained elevated even in remission. In contrast, an improvement in clinical signs and symptoms was associated with a marked reduction in circulating MMP3 and MMP9 levels in all patients (p less than 0.05). Matsuyama et al. (2003) concluded that MMP2 could be helpful in diagnosing Takayasu arteritis and that MMP3 and MMP9 could be used as activity markers for the disease. p> Mapping <p>Terao et al. (2013) performed genome scanning of 167 Takayasu arteritis cases and 663 healthy controls, followed by a replication study consisting of 212 Takayasu arteritis cases and 1,322 controls. Terao et al. (2013) found that the IL12B (161561) region on chromosome 5 (rs6871626) (overall p = 1.7 x 10(-13), OR = 1.75, 95% confidence interval 1.42-2.16) and the MLX (602976) region on chromosome 17 (rs665268) (overall p = 5.2 x 10(-7), OR = 1.50, 95% confidence interval 1.28-1.76) as well as the HLA-B (142830) region (rs9263739) (a proxy of HLA-B*52:01, overall p = 2.8 x 10(-21), OR = 2.44, 95% confidence interval 2.03-2.93) exhibited significant associations. A significant synergistic effect of rs6871626 and rs9263739 was found with a relative excess risk of 3.45, attributable proportion of 0.58, and synergy index of 3.24 (p less than or equal to 0.00028) in addition to a suggestive synergistic effect between rs665268 and rs926379 (p less than or equal to 0.027). Terao et al. (2013) also found that rs6871626 showed a significant association with clinical manifestations of Takayasu arteritis, including increased risk and severity of aortic regurgitation. Terao et al. (2013) concluded that their findings indicated that IL12B plays a fundamental role in the pathophysiology of Takayasu arteritis in combination with HLA-B*52:01, and that common autoimmune mechanisms underlie the pathology of Takayasu arteritis and other autoimmune disorders such as psoriasis (see PSORS11, 612599) and inflammatory bowel diseases (see IBD19, 612278) in which IL12B is involved as a genetic predisposing factor. p><p>Saruhan-Direskeneli et al. (2013) genotyped approximately 200,000 genetic variants in 2 ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform. Additional genetic variants and the classic HLA alleles were imputed and analyzed. Saruhan-Direskeneli et al. (2013) identified and confirmed 2 independent susceptibility loci within the HLA region (r(2) less than 0.2): HLA-B (142830)/MICA (600169) (rs12524487, OR = 3.29, p = 5.57 x 10(-16)) and HLA-DQB1 (604305)/HLA-DRB1 (142857) (rs113452171, OR = 2.34, p = 3.74 x 10(-9); and rs189754752, OR = 2.47, p = 4.22 x 10(-9)). In addition, Saruhan-Direskeneli et al. (2013) identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A (146790)/FCGR3A (146740) locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 x 10(-12)). The risk allele in this locus results in increased mRNA expression of FCGR2A. Saruhan-Direskeneli et al. (2013) also established a genetic association between IL12B and Takayasu arteritis at rs56167332 (OR = 1.54, p = 2.18 x 10(-8)). p>