The PCSK9 Gene: Relationship to Human Health
Select sequence variations in PCSK9 that result in low plasma LDL-cholesterol have been identified in family DHS20 (study #1287-355). So far, family members with no affected alleles, one affected allele and both affected alleles have been identified. While plasma levels of LDL-cholesterol vary according to the number of affected alleles, no additional differences in physiologic parameters have been observed. In addition, we continue to identify further families with sequence variations in PCSK9 resulting in low plasma LDL. To ensure that the absence of PCSK9 does not confer additional physiologic change beyond its effect on plasma LDL-cholesterol, we wish to perform a comprehensive clinical evaluation of subjects with absent, low and normal levels of plasma PCSK9. Ultimately, the goal of the project is to determine if the absence of circulating PCSK9 is related to clinical pathology within and beyond the organs in which PCSK9 is expressed. Participation will be limited to two study visits at the CTRC lasting approximately 8 hours each.
•Family members of the proband from family DHS20 with no, one or two mutations in the PCSK9 gene – initially, we will evaluate DHS20-2 (compound heterozygote) and DHS20-4 (wild type)
•Members of additional families identified to have one or two mutations in the PCSK9 gene
•Subjects must be greater than or equal to 18 years of age and not older than 100 years of age