M. Gallegos-arreola et al., Linkage disequilibrium between IDUA kpnI-VNTR haplotype in Mexican patients with MPS-I, ARCH MED R, 30(5), 1999, pp. 375-379
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.