Relation of PCSK9 mutations to serum low-density lipoprotein cholesterol in childhood and adulthood (from the bogalusa heart study)

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 I 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 noricarriers (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. (C) 2007 Elsevier Inc. All rights reserved.