Linkage disequilibrium between IDUA kpnI-VNTR haplotype in Mexican patients with MPS-I

Background. The MPS-I is an autosomal recessive disorder caused by mutation s in the IDUA gene that induce to a deficiency of glycosidase alpha-L-iduro nidase that is required for degradation of heparan and dermatan sulfate. Th is disorder expresses a wide range of clinical symptoms. Methods. KpnI (K) and VNTR (V) intragenic polymorphisms at the IDUA gene we re 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 wer e also studied. Results, Genotypes for IDUA K and V sites in Mexicans were in agreement wit h 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 the se two normal groups were also different as compared with normal Australian s. 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 s imilar finding was reported. However, disequilibrium in Mexicans was determ ined by haplotypes different from those in Australia. In Mexican MPS-I pati ents, 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 incr ease of haplotypes K2-V2 and K1-V2 with respect to expected frequency. Conclusions. The similar HFD between Mexican and Australian MPS-I patients suggests a common genetic origin, that MPS-I mutations were introduced to M exico by Spaniards, and that such mutations predate the dispersion between Mexican and Australian Caucasian ancestors, The differences in disequilibri um are explained rather by genetic drift. (C) 1999 IMSS. Published by Elsev ier Science Inc.