THE GENE RESPONSIBLE FOR AUTOIMMUNE POLYGLANDULAR SYNDROME TYPE-1 MAPS TO CHROMOSOME 21Q22.3 IN US PATIENTS

Autoimmune polyglandular syndrome type 1 [APS-1] comprises multiple or gan-specific autoimmunities such as acquired hypoparathyroidism and au toimmune Addison's disease, and a predisposition to certain infections such as chronic mucocutaneous candidiasis. An APS-I candidate gene wa s assigned to chromosome 21q22.3 by linkage analyses in patients with APS-1 from Finland. To examine the influence of ethnic and geographic differences on the location of the candidate gene locus, we studied 24 US patients with APS-1 by microsatellite marker typing, using five mi crosatellite markers, D21S49, PFKL, D21S171, D21S1903 and CD18, select ed from chromosome 21q22.3. By allelic association analyses, the frequ encies of allele number 5 for D21S171 and allele number 8 for D21S1903 were significantly higher in the 24 patients with APS-1 than in 33 co ntrols (33/48 vs. 31/66, P=0.0207, X-2=5.35; 12/48 vs. 7/66, P=0.0418, X-2=4.15 respectively). The frequency of homozygosity for allele numb er 5 of D21S171 was also significantly higher in the patients than in controls, 15/24 vs. 9/33 (P=0.0078, X-2=7.07). Maximum lod scores dete cted for the five markers in nine families (containing 15 of the patie nts with APS-1) were: 2.384 for D21S49, 3.144 for PFKL, 3.506 for D21S 171, 4.329 for D21S1903, and 1.130 for CD18. These results confirm the linkage of the candidate APS-1 gene to 21q22.3 in US APS-1 patients, and suggest that the candidate gene is located near the D21S1903 marke r. The demonstration of the location of the APS-1 candidate gene to 21 q22.3 in an out-bred heterogeneous patient population should promote t he physical mapping of the responsible gene. (C) 1998 Academic Press L imited.