Including HMGB1 and osteoprotegerin in the multivariable analysis in model 2, HMGB1 and osteoprotegerin remained independently associated with unstable plaque in ICAS patients, and the conventional risk factors in model 1 remained determinants of unstable plaque even in model 2 (Table 5). The gene discussed is TNFRSF11B; the disease is familial isolated congenital asplenia.