Familial defective apolipoprotein B-100: AÂ review

•FDB affects approximately one in 1000 US Caucasians and Europeans•On average, heterozygous APOB R3500Q raises LDL-C by approximately 60 to 70 mg per dL•FDB affects certain groups, such as the Swiss and Amish, at elevated rates.•FDB makes a significant contribution to FH among Han Chinese.•Standard diagnostic criteria underdiagnose FDB.

Familial defective apolipoprotein B-100 (FDB) is an autosomal dominant genetic disorder of lipid metabolism associated with hyperlipidemia and elevated risk for atherosclerosis. FDB is caused by mutations in APOB reducing the binding affinity between apolipoprotein B-100 and the low-density lipoprotein receptor. Population studies suggest that approximately 0.1% of Northern Europeans and US Caucasians carries the R3500Q variant in APOB most commonly associated with FDB; in addition, the APOB R3500 W variant is known to make a significant contribution to familial hypercholesterolemia (FH) among East Asians. However, the elevation of plasma low-density lipoprotein cholesterol observed in FDB is frequently milder than that of FH due to mutations in LDLR, and FDB is subsequently underdiagnosed according to standard FH diagnostic criteria.