Browsing by Author "Blackhurst, D. M."

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    Indices of paraoxonase and oxidative status do not enhance the prediction of subclinical cardiovascular disease in mixed-ancestry South Africans
    (Hindawi Publishing Corporation, 2014-03-27) Macharia, M.; Kengne, A. P.; Blackhurst, D. M.; Erasmus, R. T.; Hoffmann, M.; Matsha, T. E.
    We evaluated the association of indices of paraoxonase (PON1) and oxidative status with subclinical cardiovascular disease (CVD) in mixed-ancestry South Africans. Participantswere 491 adults (126 men)whowere stratified by diabetes status and bodymass index (BMI). Carotid intima-media thickness (CIMT) was used as a measure of subclinical CVD. Indices of PON1 and oxidative status were determined by measuring levels and activities (paraoxonase and arylesterase) of PON1, antioxidant activity (ferric reducing antioxidant power and trolox equivalent antioxidant capacity), and lipid peroxidation markers (malondialdehyde and oxidized LDL). Diabetic subjects (28.9%) displayed a significant decrease in PON1 status and antioxidant activity as well as increase in oxidized LDL and malondialdehyde. A similar profile was apparent across increasing BMI categories. CIMT was higher in diabetic than nondiabetic subjects (P < 0.0001) but showed no variation across BMI categories. Overall, CIMT correlated negatively with indices of antioxidant activity and positivelywithmeasures of lipid oxidation. Sex, age, BMI, and diabetes altogether explained 29.2% of CIMT,with no further improvement fromadding PON1 and/or antioxidant status indices.Though indices of PON1 and oxidative status correlate with CIMT, their measurements may not be useful for identifying subjects at high CVD risk in this population.
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    Paraoxonase 1 genetic polymorphisms in a mixed ancestry African population
    (Hindawi Publishing Corporation, 2014-11-16) Macharia, M.; Kengne, A. P.; Blackhurst, D. M.; Erasmus, R. T.; Matsha, T. E.
    Paraoxonase 1 (PON1) activity is markedly influenced by coding polymorphisms, Q/R at position 192 and M/L at position 55 of the PON1 gene. We investigated the frequencies of these polymorphisms and their effects on PON1 and antioxidant activities in 844 South African mixed ancestry individuals. Genotyping was done using allele-specific TaqMan technology, PON1 activities were measured using paraoxon and phenylacetate, oxidative status was determined by measuring the antioxidant activities of ferric reducing antioxidant power and trolox equivalent antioxidant capacity, and lipid peroxidation markers included malondialdehyde and oxidized LDL. The frequencies of Q192R and L55Mwere 47.6% and 28.8%, respectively, and the most common corresponding alleles were 192R (60.4%) and 55M (82.6%).The Q192 was significantly associated with 5.8 units’ increase in PON1 concentration and 15.4 units’ decrease in PONase activity after adjustment for age, sex, BMI, and diabetes, with suggestion of differential effects by diabetes status.The PON1 L55 variant was associated with none of the measured indices. In conclusion, we have shown that the Q192R polymorphism is a determinant of both PON1 concentration and activity and this association appeared to be enhanced in subjects with diabetes.