GENOTYPE ASSOCIATIONS AMONG 7 APOLIPOPROTEIN-B POLYMORPHISMS IN A POPULATION OF ORANG-ASLI OF WESTERN MALAYSIA

Associations among seven apolipoprotein B (APOB) gene polymorphisms [C -T promoter site; Leu-Ala-Leu signal peptide (SP) insertion/deletion; AG C,G site at codon 71; AG A1,D site at codon 591; XbaI site at codon 2488; AG H,I site at codon 3611; and AG T,Z site at codon 4154] were investigated in 195 members of an Orang Asli (aborigine) population fr om western Malaysia. Frequencies of the rare alleles for all these pol ymorphisms turned out to be low when compared with European but not As ian populations. The AG H,I site was not polymorphic. The highly polym orphic sites are in linkage disequilibrium among themselves, as shown by their Delta values: SP 24,27 and AG C,G, 0.68; SP 24,27 and AG A1,D , 0.71;XbaI and AC C,G, 0.64; XbaI and AG A1,D, 0.57; SP 24,27 and Xba I, 0.48; and AG C,G and AG A1,D, 0.68. Ten unequivocal haplotypes on t he basis of six sites (excluding the promoter polymorphism) were obser ved, and they represent 80% of the sample. The frequency of haplotype SP27,G,A1,X -,I,T, defined by the common homozygotes at all the sites for the APOB gene was 0.7, compared with 0.22 in Europeans. The ancest ral haplotype SP27,G,D,X -,I,T was present at low frequency (0.01) in both the Orang Asli and Europeans. A cladogram constructed on the basi s of haplotypes in the Orang Asli shows two different lines of evoluti on and that other haplotypes evolved by subsequent mutations on the an cestral haplotype.