An abundance of population-specific monomorphic SNPs may or may not be meaningful: A commentary on differences in allele frequencies of familial hypercholesterolemia SNPs in the Malaysian population

摘要

In previous issue of the Journal of Human Genetics, Alex et al.1 report the differences in allele frequencies of familial hypercho-lesterolemia (FH) single-nucleotide polymorphisms (SNPs) in the Malaysian population. As one of the most common inherited disorders in humans, autosomal dominant hypercholesterolemia (ADH) (MIM #143890) or its more common name, FH is caused predominantly by mutations in LDLR in the majority of patients. Additionally, less strong but important associations were also identified for ApoE and PCSK9. Either heterozygous or homozygous mutations in these genes undoubtedly led to hypercholesterolemia ranging from mild-to-severe phenotypes. However, these findings underplay several previous studies highlighting the importance of SNPs as genetic modifying factors in ADH, which affect cholesterol regulation differently across populations (reviewed in Fahed and Nemer2).