Linkage disequilibrium between S65C HFE mutation and HLA A29-B44 haplotype in Terceira Island, Azores

Our objective was to investigate the frequency of HFE gene mutations and to study linkage disequilibrium (LD) between HLA-Class I alleles and these mutations in the population of Terceira Island, Azores, Portugal. A total of 218 unrelated individuals were investigated. Three HFE mutations--C282Y, H63D, and S65C--were identified by restriction endonuclease digestion of polymerase chain reaction (PCR)-amplified genomic DNA. HLA-Class I alleles were typed by PCR-single-strand polymorphism. Gene frequencies and LD were estimated using Arlequin V 1.1. Six genotypes were found in the population: WT/WT (58.3%), H63D/WT (31.2%), H63D/H63D (2.3%), H63D/C282Y (0.9%), S65C/WT (4.1%), and C282Y/WT (3.2%). No cases of C282Y or S65C homozygosity were identified. HLA haplotype A3-B7 was in LD with C282Y; HLA alleles A29, B44, and HLA haplotype A29-B44 were in LD with S65C mutation. HFE gene frequencies in this population are similar to those in other European populations; HFE S65C mutation was found in LD with the alleles A29, B44, and with A29-B44 HLA haplotype.