C679X loss-of-function PCSK9 variant is associated with lower fasting glucose in black South African adolescents: Birth to Twenty Plus Cohort

Aim: To evaluate the association between loss-of-function (LOF) PCSK9 variants (A433T/rs28362263 and C679X/rs28362286) and biomarkers of cardiometabolic risk, specifically fasting glucose and low density lipoprotein cholesterol (LDL-C) concentrations. Methods: Our study comprised 757 male and female black South African adolescents (mean age 18.0 +/- 0.5 years) who are part of the Birth to Twenty Plus Cohort and had been genotyped for the two above-mentioned variants. Anthropometric measures were completed and fasting plasma glucose and lipid analysis were performed using standard procedures. Results: The median and interquartile range of fasting glucose and LDL-C for the whole group were 4.60 (4.36-4.88) mmol/L and 1.67 (1.25-2.14) mmol/L, respectively. After adjusting for sex, association between the biomarkers and A443T was not significant. However, C679X carriers displayed 0.30 [95% CI (-0.57, -0.02); p = 0.035] mmol/L lower fasting glucose and 0.50 [95% CI (-0.74, -0.26); p < 0.001) mmol/L lower LDL-C concentrations compared to non-carriers. Conclusions: Our results indicate for the first that the C679X variants associated with low fasting glucose levels during adolescents as had been known for LDL-C. In view that a similar finding was reported in older black South African adults, therefore, the correlation of lower fasting glucose and LDL-C levels with C679X is observed from an early age to adulthood.