Familial evidence of vasospastic angina and possible involvement of HLA-DR2 in susceptibility to coronary spasm.

An association between genetic factors and susceptibility to coronary spasm has not been proven. Because we encountered 7 patients with familial occurrence of vasospastic angina (VSA) in 3 families, the association of a genetic factor with coronary spasm was assumed. HLA typing as one of the genetic markers was performed in the 3 families, and the affected members in each family were found to share a HLA haplotype, carrying both HLA-DR52 and DQ6. This raised the possibility that one of the susceptibility genes for coronary spasm is located in the HLA region. To assess this possibility, HLA typing was performed and compared in 110 patients with VSA but without a family history of VSA (VSA group) and 55 patients with chest pain syndrome (CPS group) as control subjects. All patients underwent a provocation test for coronary spasm, and spasm was angiographically documented in the VSA group but not in the CPS group. Of all HLA antigens, the frequency of only HLA-DR2 was significantly higher in the VSA group than in the CPS group (39.1% vs 18.2%, p<0.01). The result implied that HLA-DR2 is in linkage disequilibrium with a susceptibility gene of VSA and thus is possibly involved in susceptibility to coronary spasm in some patients with VSA.