Chikowore, TSahibdeen, VHendry, L.MNorris, S.AGoedecke, J.HMicklesfield, L.KLombard, Z2025-01-092025-01-092019-02-28Chikowore T, Sahibdeen V, Hendry LM, Norris SA, Goedecke JH, Micklesfield LK, Lombard Z. C679X loss-of-function PCSK9 variant is associated with lower fasting glucose in black South African adolescents: Birth to Twenty Plus Cohort. J Clin Transl Endocrinol. 2019 Feb 28;16:100186. doi: 10.1016/j.jcte.2019.100186.https://pubmed.ncbi.nlm.nih.gov/30899674/https://doi.org/10.1016/j.jcte.2019.100186https://hdl.handle.net/11288/598066Aim 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.enC679XFasting glucoseLDL-CPCSK9Type 1 diabetesArticle