Rare Mutations of Peroxisome Proliferator-Activated Receptor Gamma: Frequencies and Relationship with Insulin Resistance and Diabetes Risk in the Mixed Ancestry Population from South Africa

Background. Genetic variants in the nuclear transcription receptor, PPARG, are associated with cardiometabolic traits, but reports remain conflicting. We determined the frequency and the clinical relevance of PPARG SNPs in an African mixed ancestry population. Methods. In a cross-sectional study, 820 participants were genotyped for rs1800571, rs72551362, rs72551363, rs72551364, and rs3856806, using allele-specific TaqMan technology. The homeostatic model assessment of insulin (HOMA-IR), β-cells function (HOMA-B%), fasting insulin resistance index (FIRI), and the quantitative insulin-sensitivity check index (QUICKI) were calculated. Results. No sequence variants were found except for the rs3856806. The frequency of the PPARG-His447His variant was 23.8% in the overall population group, with no difference by diabetes status (). The His447His allele T was associated with none of the markers of insulin resistance overall and by diabetes status. In models adjusted for 2-hour insulin, the T allele was associated with lower prevalent diabetes risk (odds ratio 0.56 (95% CI 0.31–0.95)). Conclusion. Our study confirms the almost zero occurrences of known rare PPARG SNPs and has shown for the first time in an African population that one of the common SNPs, His447His, may be protective against type 2 diabetes

APOL1 genetic variants, chronic kidney diseases and hypertension in mixed ancestry South Africans

BackgroundThe frequencies of apolipoprotein L1 (APOL1) variants and their associations with chronic kidney disease (CKD) vary substantially in populations from Africa. Moreover, available studies have used very small sample sizes to provide reliable estimates of the frequencies of these variants in the general population. We determined the frequency of the two APOL1 risk alleles (G1 and G2) and investigated their association with renal traits in a relatively large sample of mixed-ancestry South Africans. APOL1 risk variants (G1: rs60910145 and rs73885319; G2: rs71785313) were genotyped in 859 African mixed ancestry individuals using allele-specific TaqMan technology. Glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations.ResultsThe frequencies of rs73885319, rs60910145 and rs71785313 risk alleles were respectively, 3.6%, 3.4%, and 5.8%, resulting in a 1.01% frequency of the APOL1 two-risk allele (G1:G1 or G1:G2 or G2:G2). The presence of the two-risk allele increased serum creatinine with a corresponding reduction in eGFR (either MDRD or CKD-EPI based). In dominant and log-additive genetic models, significant associations were found between rs71785313 and systolic blood pressure (both p ≤ 0.025), with a significant statistical interaction by diabetes status, p = 0.022, reflecting a negative non-significant effect in nondiabetics and a positive effect in diabetics.ConclusionsAlthough the APOL1 variants are not common in the mixed ancestry population of South Africa, the study does provide an indication that APOL1 variants may play a role in conferring an increased risk for renal and cardiovascular risk in this population

Determination of the Gamow-Teller Quenching Factor from Charge Exchange Reactions on 90Zr

Double differential cross sections between 0-12 degrees were measured for the 90Zr(n,p) reaction at 293 MeV over a wide excitation energy range of 0-70 MeV. A multipole decomposition technique was applied to the present data as well as the previously obtained 90Zr(p,n) data to extract the Gamow-Teller (GT) component from the continuum. The GT quenching factor Q was derived by using the obtained total GT strengths. The result is Q=0.88+/-0.06 not including an overall normalization uncertainty in the GT unit cross section of 16%.Comment: 11 papes, 4 figures, submitted to Physics Letters B (accepted), gzipped tar file, changed content

Analyzing power for the proton elastic scattering from neutron-rich 6He nucleus

Vector analyzing power for the proton-6He elastic scattering at 71 MeV/nucleon has been measured for the first time, with a newly developed polarized proton solid target working at low magnetic field of 0.09 T. The results are found to be incompatible with a t-matrix folding model prediction. Comparisons of the data with g-matrix folding analyses clearly show that the vector analyzing power is sensitive to the nuclear structure model used in the reaction analysis. The alpha-core distribution in 6He is suggested to be a possible key to understand the nuclear structure sensitivity.Comment: 5 pages, 3 figures, accepted for publication as a Rapid Communication in Physical Review

Precision measurement of vector and tensor analyzing powers in elastic deuteron-proton scattering

High precision vector and tensor analyzing powers of elastic deuteron-proton d+p scattering have been measured at intermediate energies to investigate effects of three-nucleon forces (3NF). Angular distribution in the range of 70-120 degree in the center-of mass frame for incident-deuteron energies of 130 and 180 MeV were obtained using the RIKEN facility. The beam polarization was unambiguously determined by measuring the 12C(d,alpha)10B(2+) reaction at 0 degree. Results of the measurements are compared with state-of-the-art three-nucleon calculations. The present modeling of nucleon-nucleon forces and its extension to the three-nucleon system is not sufficient to describe the high precision data consistently and requires, therefore, further investigation

Association of the ENPP1 rs997509 polymorphism with obesity in South African mixed ancestry learners

Background: The Ectonucleotide Pyrophosphatase Phosphodiesterase1 (ENPP1) polymorphisms have been associated with metabolic traits. There is no data on the effect of ENPP1 in South African children or adults. Objective: To investigate the role of K121Q (rs1044498), rs997509 and rs9402349 in obesity and other components of the metabolic syndrome. Design: A case-control study. Subjects: Sixty four obese and 64 lean mixed ancestry learners. Setting: Western Cape, South Africa. Main outcome measure: The EN PP1 rs997509T allele is independently associated with obesity in children of mixed ancestry from South Africa. Results: The T allele frequency of the rs997509 differed significantly between obese and controls, p=0.0100 and increased the risk of being obese, p = 0.0238. Furthermore, the estimated effect of the T allele was an increase of 8.6 cm in waist circumference, 10.2 kg in weight and a corresponding 4.9 kg/m2 in BMI. Individuals carrying both the 121Q and the T allele of rs997509 were more associated with obesity (odds ratio = 3.85, 95% CI: 1.13 to 13.09) whilst those carrying the C allele of rs997509 in the presence of 121Q were likely to be lean with odds ratio of obesity 0.41 (95% CI: 0.19 to 0.87). Conclusion: Our findings suggest that ENPP1 polymorphisms may contribute to different metabolic characteristics, all of which are associated with insulin resistance in mixed ancestry children of South Africa. However, a larger study is required to confirm findings of this study.East African Medical Journal Vol. 87 No. 8 August 201

Performance of the neutron polarimeter NPOL3 for high resolution measurements

We describe the neutron polarimeter NPOL3 for the measurement of polarization transfer observables $D_{ij}$ with a typical high resolution of $\sim$300 keV at $T_n$ $\simeq$ 200 MeV. The NPOL3 system consists of three planes of neutron detectors. The first two planes for neutron polarization analysis are made of 20 sets of one-dimensional position-sensitive plastic scintillation counters with a size of 100 cm $\times$ 10 cm $\times$ 5 cm, and they cover the area of 100 $\times$ 100 $\mathrm{cm}^2$. The last plane for detecting doubly scattered neutrons or recoiled protons is made of the two-dimensional position-sensitive liquid scintillation counter with a size of 100 cm $\times$ 100 cm $\times$ 10 cm. The effective analyzing powers $A_{y;\mathrm{eff}}$ and double scattering efficiencies $\epsilon_{\mathrm{D.S.}}$ were measured by using the three kinds of polarized neutrons from the ${}^{2}{\rm H}(\vec{p},\vec{n})pp$, ${}^{6}{\rm Li}(\vec{p},\vec{n}){}^{6}{\rm Be}(\mathrm{g.s.})$, and ${}^{12}{\rm C}(\vec{p},\vec{n}){}^{12}{\rm N}(\mathrm{g.s.})$ reactions at $T_p$ = 198 MeV. The performance of NPOL3 defined as $\epsilon_{\mathrm{D.S.}}(A_{y;\mathrm{eff}})^2$ are similar to that of the Indiana Neutron POLarimeter (INPOL) by taking into account for the counter configuration difference between these two neutron polarimeters.Comment: 28 pages, 18 figures, submitted to Nucl. Instrum. Methods Phys. Res.

Inflammatory cytokines and combined biomarker panels in pancreatic ductal adenocarcinoma: Enhancing diagnostic accuracy

BackgroundEarly diagnosis of pancreatic ductal adenocarcinoma (PDAC) is challenged by the absence of accurate early diagnostic and prognostic biomarkers. CA19-9 is the established, diagnostic tumour marker in PDAC, despite its limitations. Effective primary screening using circulating biomarker panels have only been considered in a handful of studies and we investigated whether combinations of inflammatory cytokines and angiogenic factors in multivariate logistic models could facilitate earlier diagnosis in our South African setting.MethodsPlasma levels of 38 cytokines and angiogenic factors were measured in 131 Black South African patients, 85 with PDAC, 25 with benign biliary pathology (BBP) and 21 benign non-HPB controls (BC), by use of human magnetic multiplex screening assays. Multivariate biomarker panels were developed by identifying the top performing biomolecules from univariate logistic regression. Receiver-operator characteristic (ROC) curves and area under the ROC curve (AUC) are reported.ResultsClassification modelling to distinguish PDAC patients from BC showed that a panel of CA19-9 and CXCL10 (IP-10) demonstrated improved diagnostic power over CA19-9 alone (AUC = 0.977 vs. AUC = 0.807, p-value = 0.001). A combined panel including age, BMI and IL-15 showed significant diagnostic power in discriminating PDAC from BBP (AUC = 0.952, p ConclusionsCombined biomarker panels improve diagnostic accuracy in PDAC. In addition to CA19-9, cytokines CXCL10, IL-8 and IL-15 are strong additions to diagnostic biomarker panels in PDAC in Black South Africans

Optimal waist-to-height ratio values for cardiometabolic risk screening in an ethnically diverse sample of South African urban and rural school boys and girls

BACKGROUND: The proposed waist-to-height ratio (WHtR) cut-off of 0.5 is less optimal for cardiometabolic risk screening in children in many settings. The purpose of this study was to determine the optimal WHtR for children from South Africa, and investigate variations by gender, ethnicity and residence in the achieved value. METHODS: Metabolic syndrome (MetS) components were measured in 1272 randomly selected learners, aged 10-16 years, comprising of 446 black Africans, 696 mixed-ancestry and 130 Caucasians. The Youden's index and the closest-top-left (CTL) point approaches were used to derive WHtR cut-offs for diagnosing any two MetS components, excluding the waist circumference. RESULTS: The two approaches yielded similar cut-off in girls, 0.465 (sensitivity 50.0, specificity 69.5), but two different values in boys, 0.455 (42.9, 88.4) and 0.425 (60.3, 67.7) based on the Youden's index and the CTL point, respectively. Furthermore, WHtR cut-off values derived differed substantially amongst the regions and ethnic groups investigated, whereby the highest cut-off was observed in semi-rural and white children, respectively, Youden's index0.505 (31.6, 87.1) and CTL point 0.475 (44.4, 75.9). CONCLUSION: The WHtR cut-off of 0.5 is less accurate for screening cardiovascular risk in South African children. The optimal value in this setting is likely gender and ethnicity-specific and sensitive to urbanization