THE HEMOCHROMATOSIS 845-G-]A AND 187-C-]G MUTATIONS - PREVALENCE IN NON-CAUCASIAN POPULATIONS

Hemochromatosis, the inherited disorder of iron metabolism, leads, if untreated, to progressive iron overload and premature death. The hemoc hromatosis gene, HFE, recently has been identified, and characterizati on of this gene has shown that it contains two mutations that result i n amino acid substitutions-cDNA nucleotides 845 G-->A (C282Y) and 187 C-->G (H63D). Although hemochromatosis is common in Caucasians, affect ing greater than or equal to 1/300 individuals of northern European or igin, it has not been recognized in other populations. The present stu dy used PCR and restriction-enzyme digestion to analyze the frequency of the 845 G-->A and 187 C-->G mutations in HLA-typed samples from non -Caucasian populations, comprising Australian Aboriginal, Chinese, and Pacific Islanders. Results showed that the 845 G-->A mutation was pre sent in these populations (allele frequency 0.32%), and, furthermore, it was always seen in conjunction with HLA haplotypes common in Caucas ians, suggesting that 845 G-->A may have been introduced into these po pulations by Caucasian admixture. 187 C-->G was present at an allele f requency of 2.68% in the two populations analyzed (Australian Aborigin al and Chinese). In the Australian Aboriginal samples, 187 C-->G was f ound to be associated with HLA haplotypes common in Caucasians, sugges ting that it was introduced by recent admixture. In the Chinese sample s analyzed,:187 C-->G was present in association with a wide variety o f HLA haplotypes, showing this mutation to be widespread and likely to predate the more genetically restricted 845 G-->A mutation.