HUMAN MUSCLE ACETYLCHOLINE-RECEPTOR ALPHA-SUBUNIT GENE (CHRNA1) ASSOCIATION WITH AUTOIMMUNE MYASTHENIA-GRAVIS IN BLACK, MIXED-ANCESTRY AND CAUCASIAN SUBJECTS

We have sought associations with the muscle acetylcholine receptor alp ha-subunit gene (CHRNA1) in autoimmune myasthenia gravis (MG) patients from three ethnic groups; Caucasians and South Africans of Black and Mixed-Ancestry. We found a significant association with the HB15 CA r epeat allele in unrelated Black myasthenics (n=18; RR=2.85; pX(2)=0.04 ) compared with 52 ethnically matched controls. A family-based associa tion study and linkage analysis in Caucasian simplex and multiplex fam ilies supported a positive association at this locus with the longer a lleles, including HB14 to *18. However, no significant cosegregation of the disease with the HE alleles could be demonstrated in affected s ib pairs. Our results suggest that the CHRNA1 locus harbours a minor s usceptibility gene for developing MG, though we cannot rule out linkag e disequilibrium with another major gene locus on chromosome 2. (C) 19 96 Academic Press Limited