FAMILIAL DEFECTIVE APOLIPOPROTEIN B-100 IN HYPERCHOLESTEROLEMIC CHINESE CANADIANS - IDENTIFICATION OF A UNIQUE HAPLOTYPE OF THE APOLIPOPROTEIN B-100 ALLELE

Familial defective apo B-100 (FDB) is an autosomal dominant condition resulting in hypercholesterolemia. It is generally observed in 1-6% of hypercholesterolemic subjects in Caucasian populations studied. There are, thus far, no reports characterizing the frequency and phenotype of FDB in a Chinese population. We report on the frequency of the FDB (Arg((3500))-->Gln) mutation and the associated haplotype among 160 hy percholesterolemic (TC greater than or equal to 6.2 mmol/l) Chinese Ca nadians including 36 subjects with a clinical diagnosis of familial hy percholesterolemia (FH). Screening for the FDB mutation was done using a mutagenic polymerase chain reaction and haplotype analysis was unde rtaken using eight diallelic markers and the 3'HVR marker. One Chinese Canadian clinical FH heterozygote was positive for the FDB Arg((3500) )-->Gln mutation while none of the remaining non-FH hypercholesterolem ic subjects (n = 124) were carriers of this mutation. Haplotype analys is in the patient positive for this mutation revealed a unique haploty pe which differed from both the common haplotype of this mutation obse rved in Caucasians and from the only other haplotype reported in a Chi nese individual. The associated haplotype included a 9-base pair delet ion in the signal peptide region and the presence of three restriction sites absent in previously reported haplotypes. These data suggest th at the apo B-100 Arg((3500))-->Gln mutation does not appear to be a si gnificant factor contributing to moderate hypercholesterolemia in a Ch inese population residing in Canada. However? this mutation was rarely observed among Chinese individuals with a clinical diagnosis of FH. T he presence among Chinese individuals of two different haplotypes asso ciated with this mutation, which are different from what has been desc ribed among Caucasians is compatible with multiple recurrent origins f or this mutation in the Chinese population. (C) 1997 Elsevier Science Ireland Ltd.