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

• Published in: Journal of clinical & translational endocrinology Vol. 16; p. 100186
• Main Authors: Chikowore, Tinashe, Sahibdeen, Venesa, Hendry, Liesl M, Norris, Shane A, Goedecke, Julia H, Micklesfield, Lisa K, Lombard, Zané
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-06-2019; Elsevier
• Subjects: C679X; Endocrinology and Metabolism; Fasting glucose; LDL-C; PCSK9; Research Paper; Type 1 diabetes; PCSK9; C679X; LDL-C; Type 1 diabetes; Fasting glucose
• ISSN: 2214-6237; 2214-6237
• DOI: 10.1016/j.jcte.2019.100186

AbstractAimTo 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. MethodsOur 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. ResultsThe 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. ConclusionsOur 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.