Chen Q Y, Lan M S, She J X, Maclaren N K
Research Institute for Children, Harahan, LA 70123, USA.
J Autoimmun. 1998 Apr;11(2):177-83. doi: 10.1006/jaut.1998.0191.
Autoimmune polyglandular syndrome type 1 [APS-1] comprises multiple organ-specific autoimmunities such as acquired hypoparathyroidism and autoimmune Addison's disease, and a predisposition to certain infections such as chronic mucocutaneous candidiasis. An APS-1 candidate gene was 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 microsatellite markers, D21S49, PFKL, D21S171, D21S1903 and CD18, selected from chromosome 21q22.3. By allelic association analyses, the frequencies 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 controls (33/48 vs. 31/66, P = 0.0207, X2 = 5.35; 12/48 vs. 7/66, P = 0.0418, X2 = 4.15 respectively). The frequency of homozygosity for allele number 5 of D21S171 was also significantly higher in the patients than in controls, 15/24 vs. 9/33 (P = 0.0078, X2 = 7.07). Maximum lod scores detected for the five markers in nine families (containing 15 of the patients with APS-1) were: 2.384 for D21S49, 3.144 for PFKL, 3.506 for D21S171, 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 marker. The demonstration of the location of the APS-1 candidate gene to 21q22.3 in an out-bred heterogeneous patient population should promote the physical mapping of the responsible gene.
1型自身免疫性多腺体综合征（APS-1）包括多种器官特异性自身免疫病，如获得性甲状旁腺功能减退症和自身免疫性艾迪生病，以及对某些感染（如慢性黏膜皮肤念珠菌病）的易感性。通过对来自芬兰的APS-1患者进行连锁分析，将一个APS-1候选基因定位于21号染色体q22.3区域。为了研究种族和地理差异对候选基因位点定位的影响，我们使用从21号染色体q22.3区域选取的5个微卫星标记（D21S49、PFKL、D21S171、D21S1903和CD18），通过微卫星标记分型对24例美国APS-1患者进行了研究。通过等位基因关联分析，在24例APS-1患者中，D21S171的5号等位基因频率和D21S1903的8号等位基因频率显著高于33例对照（分别为33/48对31/66，P = 0.0207，X2 = 5.35；12/48对7/66，P = 0.0418，X2 = 4.15）。D21S171的5号等位基因纯合频率在患者中也显著高于对照，为15/24对9/33（P = 0.0078，X2 = 7.07）。在9个家族（包含15例APS-1患者）中对这5个标记检测到的最大对数优势分数分别为：D21S49为2.384，PFKL为3.144，D21S171为3.506，D21S1903为4.329，CD1为1.130。这些结果证实了在美国APS-1患者中候选APS-1基因与21q22.3区域连锁，并表明候选基因位于D21S1903标记附近。在一个远交的异质患者群体中证明APS-1候选基因定位于21q22.3区域，应该会促进致病基因的物理图谱绘制。
