%0 Journal Article %J Am J Cardiol %D 2007 %T Relation of PCSK9 mutations to serum low-density lipoprotein cholesterol in childhood and adulthood (from The Bogalusa Heart Study). %A Hallman, D Michael %A Srinivasan, Sathanur R %A Chen, Wei %A Eric Boerwinkle %A Berenson, Gerald S %K Alleles %K Black or African American %K Cholesterol, LDL %K Codon, Nonsense %K Coronary Disease %K Female %K Humans %K Louisiana %K Male %K Mutation, Missense %K Proprotein Convertase 9 %K Proprotein Convertases %K Risk Factors %K Serine Endopeptidases %K White People %X

Specific mutations in the gene for proprotein convertase, subtilisin-kexin type 9 (PCSK9), that are associated with lower coronary heart disease risk may produce lifelong decreases in low-density lipoprotein (LDL) cholesterol levels, but data on their effects in younger subjects are lacking. We analyzed associations of 1 missense (R46L) and 2 nonsense (Y142X and C679X) PCSK9 mutations with serum LDL cholesterol in 478 African-Americans and 1,086 whites, 4 to 38 years of age, examined 3 to 8 times in the Bogalusa Heart Study. L46 allele frequency in whites was 0.017 +/- 0.003; the combined frequency of X142 or X679 alleles in African-Americans was 0.016 +/- 0.005. In whites, LDL cholesterol was lower in L46 carriers (78.9 +/- 21.8 mg/dl) than in noncarriers (89.7 +/- 24.9 mg/dl, p = 0.027) at their first examination (mean age 9.4 +/- 3.2 years). African-Americans carrying the X142 or X679 allele had lower LDL cholesterol levels than did noncarriers (77.3 +/- 15.1 vs 91.4 +/- 23.9 mg/dl, p = 0.043) at their first examination (mean age 9.0 +/- 3.0 years). Longitudinal LDL cholesterol profiles were significantly lower in whites with the L46 allele and in African-Americans with the X142 or X679 allele. In conclusion, our results show that these PCSK9 variants are associated with significantly lower LDL cholesterol levels starting in childhood.

%B Am J Cardiol %V 100 %P 69-72 %8 2007 Jul 01 %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/17599443?dopt=Abstract %R 10.1016/j.amjcard.2007.02.057