Gallegos-Arreola M, Rivas-Solis F, Flores-Martínez S, Zúñiga-González G, Sandoval-Ramírez L, Cantú-Garza J M, Ranaji C, Figuera L, Morán-Moguel M C, Sánchez Corona J
División de Medicina Molecular, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico.
Arch Med Res. 1999 Sep-Oct;30(5):375-9. doi: 10.1016/s0188-0128(99)00049-4.
The MPS-I is an autosomal recessive disorder caused by mutations in the IDUA gene that induce to a deficiency of glycosidase alpha-L-iduronidase that is required for degradation of heparan and dermatan sulfate. This disorder expresses a wide range of clinical symptoms.
Kpnl (K) and VNTR (V) intragenic polymorphisms at the IDUA gene were studied in mestizo and Huichol Indian Mexican populations as well in 13 MPS-I patients. Data from Australian normal and MPS-I (2-4) individuals were also studied.
Genotypes for IDUA K and V sites in Mexicans were in agreement with Hardy-Weinberg expectations, except for site K in Huichols. Individually, allele frequency distributions were different (p < 0.05) in the two normal groups for the V site. K-V haplotype frequency distributions (HFDs) in these two normal groups were also different as compared with normal Australians. In Mexican MPS-I patients, HFD was different (p < 0.05) with respect to both Mexican normal groups, and non-different when compared with normal or MPS-I Australians. This can be taken as evidence of linkage disequilibrium between K-V polymorphism and MPS-I gene mutation(s) at the IDUA region. A similar finding was reported. However, disequilibrium in Mexicans was determined by haplotypes different from those in Australia. In Mexican MPS-I patients, haplotype K2-V1 is increased and K1-V3 decreased with respect to the Mexican mestizo (p < 0.05), while in Australians, MPS-I patients had an increase of haplotypes K2-V2 and K1-V2 with respect to expected frequency.
The similar HFD between Mexican and Australian MPS-I patients suggests a common genetic origin, that MPS-I mutations were introduced to Mexico by Spaniards, and that such mutations predate the dispersion between Mexican and Australian Caucasian ancestors. The differences in disequilibrium are explained rather by genetic drift.
黏多糖贮积症I型（MPS-I）是一种常染色体隐性疾病，由艾杜糖醛酸酶（IDUA）基因突变引起，该突变导致降解硫酸乙酰肝素和硫酸皮肤素所需的α-L-艾杜糖苷酶缺乏。这种疾病表现出广泛的临床症状。
对梅斯蒂索人和惠乔尔印第安墨西哥人群以及13名MPS-I患者的IDUA基因内Kpnl（K）和可变数目串联重复序列（VNTR，V）多态性进行了研究。还研究了来自澳大利亚正常人和MPS-I（2 - 4）个体的数据。
墨西哥人IDUA基因K和V位点的基因型符合哈迪-温伯格预期，但惠乔尔人的K位点除外。单独来看，两个正常群体中V位点的等位基因频率分布不同（p < 0.05）。与澳大利亚正常人群相比，这两个正常群体中K - V单倍型频率分布（HFDs）也不同。在墨西哥MPS-I患者中，HFD与两个墨西哥正常群体相比均不同（p < 0.05），与澳大利亚正常人群或MPS-I患者相比则无差异。这可作为IDUA区域K - V多态性与MPS-I基因突变之间连锁不平衡的证据。有类似的发现报道。然而，墨西哥人群中的不平衡是由与澳大利亚不同的单倍型决定的。在墨西哥MPS-I患者中，相对于墨西哥梅斯蒂索人，单倍型K2 - V1增加而K1 - V3减少（p < 0.05），而在澳大利亚人中，MPS-I患者相对于预期频率，单倍型K2 - V2和K1 - V2增加。
墨西哥和澳大利亚MPS-I患者之间相似的HFD表明存在共同的遗传起源，即MPS-I突变是由西班牙人引入墨西哥的，并且这些突变早于墨西哥和澳大利亚白种人祖先的分散。不平衡的差异更多是由遗传漂变来解释的。
