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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...

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Autores principales: Chikowore, Tinashe, Sahibdeen, Venesa, Hendry, Liesl M., Norris, Shane A., Goedecke, Julia H., Micklesfield, Lisa K., Lombard, Zané
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407309/
https://www.ncbi.nlm.nih.gov/pubmed/30899674
http://dx.doi.org/10.1016/j.jcte.2019.100186
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author Chikowore, Tinashe
Sahibdeen, Venesa
Hendry, Liesl M.
Norris, Shane A.
Goedecke, Julia H.
Micklesfield, Lisa K.
Lombard, Zané
author_facet Chikowore, Tinashe
Sahibdeen, Venesa
Hendry, Liesl M.
Norris, Shane A.
Goedecke, Julia H.
Micklesfield, Lisa K.
Lombard, Zané
author_sort Chikowore, Tinashe
collection PubMed
description 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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spelling pubmed-64073092019-03-21 C679X loss-of-function PCSK9 variant is associated with lower fasting glucose in black South African adolescents: Birth to Twenty Plus Cohort Chikowore, Tinashe Sahibdeen, Venesa Hendry, Liesl M. Norris, Shane A. Goedecke, Julia H. Micklesfield, Lisa K. Lombard, Zané J Clin Transl Endocrinol Research Paper 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. Elsevier 2019-02-28 /pmc/articles/PMC6407309/ /pubmed/30899674 http://dx.doi.org/10.1016/j.jcte.2019.100186 Text en © 2019 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Paper
Chikowore, Tinashe
Sahibdeen, Venesa
Hendry, Liesl M.
Norris, Shane A.
Goedecke, Julia H.
Micklesfield, Lisa K.
Lombard, Zané
C679X loss-of-function PCSK9 variant is associated with lower fasting glucose in black South African adolescents: Birth to Twenty Plus Cohort
title C679X loss-of-function PCSK9 variant is associated with lower fasting glucose in black South African adolescents: Birth to Twenty Plus Cohort
title_full C679X loss-of-function PCSK9 variant is associated with lower fasting glucose in black South African adolescents: Birth to Twenty Plus Cohort
title_fullStr C679X loss-of-function PCSK9 variant is associated with lower fasting glucose in black South African adolescents: Birth to Twenty Plus Cohort
title_full_unstemmed C679X loss-of-function PCSK9 variant is associated with lower fasting glucose in black South African adolescents: Birth to Twenty Plus Cohort
title_short C679X loss-of-function PCSK9 variant is associated with lower fasting glucose in black South African adolescents: Birth to Twenty Plus Cohort
title_sort c679x loss-of-function pcsk9 variant is associated with lower fasting glucose in black south african adolescents: birth to twenty plus cohort
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407309/
https://www.ncbi.nlm.nih.gov/pubmed/30899674
http://dx.doi.org/10.1016/j.jcte.2019.100186
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