Tinashe Chikowore1, Marike Cockeran2, Karin R Conradie3, Tertia van Zyl3. 1. MRC/Wits Developmental Pathways for Health Research Unit, Department of Pediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Division of Human Genetics, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; DST-NRF Centre of Excellence in Mathematical and Statistical Sciences (CoE-MaSS), University of the Witwatersrand, Johannesburg, South Africa. Electronic address: tinashedoc@gmail.com. 2. School of Mathematical and Statistical Sciences, North West University, Potchefstroom, North West Province 2520, South Africa. 3. Center for Excellence in Nutrition, North West University, Potchefstroom, North West Province 2520, South Africa.
Abstract
AIMS: To determine the longitudinal association of the loss-of-function (LOF) PCSK9 variants (C679X and A443T), proxies of PCSK9 inhibitor drugs, with LDL-C, fasting glucose and glycated hemoglobin. METHODS: We conducted a five year, longitudinal study, nested within the Prospective Urban and Rural Epidemiology study, among 737 apparently healthy, male and female black South Africans of the North West province. Genotyping of the C679X and A443T PCSK9 variants was achieved using Taqman assays from Applied Biosystems. Generalized estimating equations were used to determine longitudinal association of the A443T and C679X PCSK9 variants with LDL-C, fasting glucose and glycated hemoglobin. RESULTS: C679X and A443T variant carriers were associated with significant reductions in LDL-C of -0.98(-1.29, -0.67) mmol/L; p < 0.001) and -0.39(-0.57, -0.20) mmol/L; p < 0.001) respectively, compared to the non-carriers. Only C679X variant was independently associated with reductions in fasting glucose of -0.37 (-0.61, -0.13) mmol/L; p = 0.002) compared to non-carriers. However, the association of the selected variants with glycated hemoglobin were not significant. C679X and A443T carriers were associated with -0.07 (-0.23, 0.09) %; p = 0.400), 0.05 (-0.13, 0.22) %; p = 0.599) of glycated haemoglobin respectively. CONCLUSION: Our results indicated that carriers of A443T and C679X variants exhibit sustained low LDL-C levels over 5 years and have varied effects on T2D biomarkers compared to non-carriers.
AIMS: To determine the longitudinal association of the loss-of-function (LOF) PCSK9 variants (C679X and A443T), proxies of PCSK9 inhibitor drugs, with LDL-C, fasting glucose and glycated hemoglobin. METHODS: We conducted a five year, longitudinal study, nested within the Prospective Urban and Rural Epidemiology study, among 737 apparently healthy, male and female black South Africans of the North West province. Genotyping of the C679X and A443TPCSK9 variants was achieved using Taqman assays from Applied Biosystems. Generalized estimating equations were used to determine longitudinal association of the A443T and C679XPCSK9 variants with LDL-C, fasting glucose and glycated hemoglobin. RESULTS:C679X and A443T variant carriers were associated with significant reductions in LDL-C of -0.98(-1.29, -0.67) mmol/L; p < 0.001) and -0.39(-0.57, -0.20) mmol/L; p < 0.001) respectively, compared to the non-carriers. Only C679X variant was independently associated with reductions in fasting glucose of -0.37 (-0.61, -0.13) mmol/L; p = 0.002) compared to non-carriers. However, the association of the selected variants with glycated hemoglobin were not significant. C679X and A443T carriers were associated with -0.07 (-0.23, 0.09) %; p = 0.400), 0.05 (-0.13, 0.22) %; p = 0.599) of glycated haemoglobin respectively. CONCLUSION: Our results indicated that carriers of A443T and C679X variants exhibit sustained low LDL-C levels over 5 years and have varied effects on T2D biomarkers compared to non-carriers.
Authors: Joaniter I Nankabirwa; John Rek; Emmanuel Arinaitwe; Jane Frances Namuganga; Sam L Nsobya; Victor Asua; Henry D Mawejje; Adrienne Epstein; Bryan Greenhouse; Isabel Rodriguez-Barraquer; Jessica Briggs; Paul J Krezanoski; Philip J Rosenthal; Melissa Conrad; David Smith; Sarah G Staedke; Chris Drakeley; Teun Bousema; Chiara Andolina; Martin J Donnelly; Moses R Kamya; Grant Dorsey Journal: Am J Trop Med Hyg Date: 2022-10-11 Impact factor: 3.707
Authors: Tinashe Chikowore; Venesa Sahibdeen; Liesl M Hendry; Shane A Norris; Julia H Goedecke; Lisa K Micklesfield; Zané Lombard Journal: J Clin Transl Endocrinol Date: 2019-02-28