Abdel-Wareth L O, Pimstone S N, Lagarde J P, Raisonnier A, Benlian P, Pritchard H, Hayden M R, Frohlich J J
Department of Pathology, University of British Columbia, Vancouver, Canada.
Atherosclerosis. 1997 Dec;135(2):181-5. doi: 10.1016/s0021-9150(97)00159-7.
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 hypercholesterolemic (TC > or = 6.2 mmol/l) Chinese Canadians including 36 subjects with a clinical diagnosis of familial hypercholesterolemia (FH). Screening for the FDB mutation was done using a mutagenic polymerase chain reaction and haplotype analysis was undertaken 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 hypercholesterolemic subjects (n = 124) were carriers of this mutation. Haplotype analysis in the patient positive for this mutation revealed a unique haplotype which differed from both the common haplotype of this mutation observed in Caucasians and from the only other haplotype reported in a Chinese individual. The associated haplotype included a 9-base pair deletion in the signal peptide region and the presence of three restriction sites absent in previously reported haplotypes. These data suggest that the apo B-100 Arg(3500)--> Gln mutation does not appear to be a significant factor contributing to moderate hypercholesterolemia in a Chinese population residing in Canada. However, this mutation was rarely observed among Chinese individuals with a clinical diagnosis of FH. The presence among Chinese individuals of two different haplotypes associated with this mutation, which are different from what has been described among Caucasians is compatible with multiple recurrent origins for this mutation in the Chinese population.
家族性载脂蛋白B-100缺陷症（FDB）是一种常染色体显性遗传病，可导致高胆固醇血症。在所研究的白种人群中，1%-6%的高胆固醇血症患者患有此病。迄今为止，尚无关于中国人群中FDB的发病率及其表型特征的报道。我们报告了160名华裔加拿大人（总胆固醇≥6.2 mmol/l）中FDB（精氨酸3500→谷氨酰胺）突变的频率及其相关单倍型，其中36人临床诊断为家族性高胆固醇血症（FH）。采用诱变聚合酶链反应筛查FDB突变，并使用8个双等位基因标记和3'高变区（3'HVR）标记进行单倍型分析。1名华裔加拿大临床FH杂合子FDB精氨酸3500→谷氨酰胺突变呈阳性，而其余非FH高胆固醇血症患者（n = 124）均未携带此突变。对该突变阳性患者的单倍型分析显示，其单倍型独特，既不同于白种人中常见的该突变单倍型，也不同于报道过的另一个中国人的单倍型。相关单倍型在信号肽区域有一个9个碱基对的缺失，且存在3个以前报道的单倍型中没有的限制性酶切位点。这些数据表明，对于居住在加拿大的华裔人群，载脂蛋白B-100精氨酸3500→谷氨酰胺突变似乎不是导致中度高胆固醇血症的重要因素。然而，在临床诊断为FH的华裔个体中，此突变很少见。华裔个体中与该突变相关的两种不同单倍型的存在，且不同于白种人中所描述的单倍型，这与该突变在中国人群中的多个复发起源是一致的。
