HYPERTROPHIC CARDIOMYOPATHY AND HUMAN-LEUKOCYTE ANTIGEN LINKAGE - DIFFERENTIATION OF 2 FORMS OF HYPERTROPHIC CARDIOMYOPATHY

To determine whether hypertrophic cardiomyopathy is associated with a human leukocyte antigen (HLA) phenotype, we tissue-typed 70 unrelated afflicted patients and 86 of their asymptomatic family members (from nine separate kindreds). Forty-five per cent of the white patients had B-12 antigen as compared to 23 per cent in matched control subjects; 69 per cent of black patients had a B 5-complex antigen as compared to 33 per cent in matched controls. Patients with a B-12 or B5-complex antigen were nonhypertensive and had family members with the disease. Patients without these antigens were severely hypertensive and had no affected family members. Linkage analysis of six families revealed a lod score of 7.7 for asymmetric septal hypertrophy and the HLA region of chromosome 6. We conclude that there is a heritable, nonhypertensive form of hypertrophic cardiomyopathy linked to the HLA loci on chromosome 6 and that a sporadic form is associated with severe, systemic hypertension. (N Engl J Med 300:877–882, 1979) HYPERTROPHIC cardiomyopathy (also known as idiopathic hypertrophic subaortic stenosis and asymmetric septal hypertrophy) is a common disorder of cardiac muscle characterized by asymmetric septal hypertrophy, systolic anterior motion of the mitral valve (in most cases) and myofiber disarray in the interventricular septum. Variable features include dynamic obstruction of the left ventricular outflow tract, malposition of the mitral leaflets and mitral regurgitation. Although studies using echocardiography have demonstrated an autosomal dominant pattern of inheritance,1 considerable controversy exists concerning the occurrence of sporadic cases2 3 4 and whether systemic hypertension may be associated with either the familial or sporadic form.5 6 7 8 To characterize the genetic. © 1979, Massachusetts Medical Society. All rights reserved.