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C679X loss-of-function variant is associated with lower fasting glucose in black South African adolescents: Birth to twenty plus cohort
Chikowore, T Sahibdeen, V Hendry, L.M Norris, S.A Goedecke, J.H Micklesfield, L.K Lombard, Z
Chikowore, T
Sahibdeen, V
Hendry, L.M
Norris, S.A
Goedecke, J.H
Micklesfield, L.K
Lombard, Z
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Abstract
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.
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Date
2019-02-28
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Elsevier
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Keywords
C679X,Fasting glucose,LDL-C,PCSK9,Type 1 diabetes
Citation
Chikowore 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.