The distribution of major histocompatibility complex class I polymorphic Alu insertions and their associations with HLA alleles in a Chinese population from Malaysia

The frequency and association of polymorphic Alu insertions (POALINs) with human leucocyte antigen (HLA) class I genes within the class I genomic region of the major histocompatibility complex (MHC) have been reported previously for three populations: the Australian Caucasian, Japanese and north-eastern Thai populations. Here, we report on the individual insertion frequency of the five POALINs within the MHC class I region, their HLA-A and HLA-B associations, the POALIN haplotype frequencies and the HLA-A/POALIN four-loci haplotype frequencies in the Malaysian Chinese population. The phylogenetic relationship of the four populations based on the five POALIN allele frequencies was also examined. In the Malaysian Chinese population, the POALIN AluyHG was present at the highest frequency (0.560), followed by AluyHJ (0.300), AluyMICB (0.170), AluyTF (0.040) and AluyHF (0.030). The most frequent five-loci POALIN haplotype of the 16 inferred haplotypes was the AluyHG single insertion haplotype at a frequency of 0.489. Strong associations were present between AluyHJ and HLA-A24, HLA-A33 and HLA-A11 and between AluyHG and HLA-A2, HLA-A24 and HLA-A11, and these were reflected by the inferred haplotype frequencies constructed from the combination of the HLA-A locus and the AluyHG, AluyHJ and AluyHF loci. The strongest association of AluyMICB was with the HLA-B54 allele (five of five), whereas the associations with the other 17 HLA-B alleles were weak, moderate or undetermined. Phylogenetic analysis of the five POALIN allele frequencies places the Malaysian Chinese closest to the Japanese and north-eastern Thai populations in the same cluster and separate to the Australian Caucasian population. The MHC POALINs are confirmed in this study to be informative genetic markers in lineage (haplotype) analysis, population genetics and evolutionary relationships, especially in studying the MHC genomic region.