Black African Population Research Articles

Comparison of equations for estimating glomerular filtration rate in screening for chronic kidney disease in asymptomatic black Africans: a cross sectional study

BackgroundSeveral equations have been developed to estimate glomerular filtration rate (eGFR). The common equations used were derived from populations predominantly comprised of Caucasians with chronic kidney disease (CKD). Some of the equations provide a correction factor for African-Americans due to their relatively increased muscle mass and this has been extrapolated to black Africans. Studies carried out in Africa in patients with CKD suggest that using this correction factor for the black African race may not be appropriate. However, these studies were not carried out in healthy individuals and as such the extrapolation of the findings to an asymptomatic black African population is questionable. We sought to compare the proportion of asymptomatic black Africans reported as having reduced eGFR using various eGFR equations. We further compared the association between known risk factors for CKD with eGFR determined using the different equations.MethodsWe used participant and laboratory data collected as part of a global reference interval study conducted by the Committee of Reference Intervals and Decision Limits (C-RIDL) under the International Federation of Clinical Chemistry (IFCC). Serum creatinine values were used to calculate eGFR using the Cockcroft-Gault (CG), re-expressed 4 variable modified diet in renal disease (4v–MDRD), full age spectrum (FAS) and chronic kidney disease epidemiology collaboration equations (CKD-EPI). CKD classification based on eGFR was determined for every participant.ResultsA total of 533 participants were included comprising 273 (51.2%) females. The 4v–MDRD equation without correction for race classified the least number of participants (61.7%) as having an eGFR equivalent to CKD stage G1 compared to 93.6% for CKD-EPI with correction for race. Only age had a statistically significant linear association with eGFR across all equations after performing multiple regression analysis. The multiple correlation coefficients for CKD risk factors were higher for CKD-EPI determined eGFRs.ConclusionsThis study found that eGFR determined using CKD-EPI equations better correlated with a prediction model that included risk factors for CKD and classified fewer asymptomatic black Africans as having a reduced eGFR compared to 4v–MDRD, FAS and CG corrected for body surface area.

Abstract A34: The genetic etiology of esophageal cancer in South African Black populations

Abstract Esophageal squamous cell carcinoma (ESCC) is common in Black populations of the sub-Saharan Africa, with high incidence regions in East and South Africa. Clinical presentation in Africa is late, and treatment is mainly palliative with a very poor prognosis. Various environmental risk factors have been identified, but the possible contribution of genetics to disease risk is an important question, which is unresolved. The aim of this project is to test the hypothesis that genetic variation in the South African Black population contributes significantly to the risk of ESCC. We have begun by testing genetic risk factors for ESCC which were identified by genome-wide association scans in other populations for association with ESCC in the South African Black population. Cases with a histologically confirmed diagnosis of ESCC and population controls were recruited, with informed consent and institutional ethical approval. All individuals were from the Black population of the Western Cape, with 98.2% being from the Xhosa ethnic group. A total of 513 ESCC cases and 820 controls were genotyped for 15 single nucleotide polymorphisms (SNPs) by validated TaqMan assays on a 7900HT (Applied Biosystems). SNPs were tested for association using an allelic chi-square test; odds ratios (OR) and 95% confidence intervals (CI) used the common allele as reference. A significance threshold of p=0.0033 was applied, from a Bonferroni multiple testing correction for 15 SNPs. No significant evidence of association was observed for the index SNPs at the previously reported loci ATP1B2, CASP8, c20orf54, HEATR3, PDE4D, PLCE1, PTPN2, RUNX1, SMG6, ST6GAL1, TMEM173 and UNC5L loci. However, the SNP rs2239815 at XBP1 on chromosome 22q12 was associated with ESCC (OR =1.41, P = 0.00087), as were 2 SNPs in CHEK2, rs4822983 (OR = 1.31, P = 0.0013) and rs1033667 (OR = 1.29, P = 0.0025). These 3 SNPs are within 70kb of each other and are in partial linkage disequilibrium in African populations. Fine-mapping of this locus will be required to determine the causal gene and variant/s driving this association. The lack of association with ESCC in the Black South African population at most of the loci previously associated in Asian GWAS suggests that at least some of these may not contribute to susceptibility to ESCC in the South African population. However, expansion of samples sizes and thus statistical power is required for more definitive exclusions, and the lower level of linkage disequilibrium (LD) across African genomes may produce a negative result if the SNP which is tagging the causal variant in Asian or European populations is in weak LD with the causal SNP in African populations. In order to address these issues we are now expanding the power and density of this study by genotyping 36 SNPs from loci of interest in 1000 South African ESCC cases and 940 controls from the Johannesburg Cancer Study by mass spectrometry using the MassArray genotyping system (Agena Bioscience). Citation Format: Wenlong Carl Chen, Hannah Bye, Marco Matejcic, Robyn Kerr, Elvira Singh, Natalie J. Prescott, Cathryn M. Lewis, Chantal Babb de Villers, Iqbal Parker, Christopher G. Mathew. The genetic etiology of esophageal cancer in South African Black populations [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr A34.

Forensic age-at-death estimation from the sternum in a black South African population

Age-at-death estimation is a crucial component of any forensic anthropological analysis. Despite a variety of research in this field, uncertainties still exist when estimating adult age. The sternum is an under-considered element in terms of adult age estimation. Previous research on an Indian population suggested that this may be a usable region of the skeleton, although results were ambivalent. This study observed the fusion phases of 461 sterna from a black South African population in an attempt to match true age of an individual with the different phases of synostosis of the manubrio-sternal and the sterno-xiphoidal junctions. The results demonstrated that the majority of sterna remain unfused throughout adult life, with complete fusion observed both in young (25 year-old) and old individuals. Significant differences were identified amongst male and female sterna, with males presenting no transitional fusion of the segments, while female sterna demonstrated fusion to a lesser extent. Overall, logistic regression results demonstrated low accuracies (62.5%) for age estimation even when the two sexes were considered separately (male=63.9%; female=61.8%). The synostosis of both junctions is hence considered highly variable and deemed unreliable for adult age-at-death estimation in the black South African population.

Is the HIV epidemic changing views on marriage aspirations? Perspectives of university students in Durban, South Africa

ABSTRACTMarriage rates in South Africa have dropped to approximately 37% in recent years. This is particularly marked in the Black African population compared to other race groups. In tandem, the prevalence of HIV in this country has risen to 12.7%, with the highest prevalence among Black Africans. However, no data associates marriage decline with high HIV prevalence. We bridge this gap in knowledge by investigating young students’ aspirations to marry in the context of high national HIV rates. A cross-sectional study was conducted among university students (n = 384) in KwaZulu-Natal, South Africa, between October and November 2014. Quantitative data were collected through self-administered questionnaires. Data was analysed by Likert scale analysis, Chi square test, Fisher’s exact test, multivariate regression modelling and calculation of odds ratios. Majority of respondents (85.8%, n = 331) indicated that they wished to get married but more than half (53%, n = 205, p < 0.001) indicated that the high prevalence of HIV has had a negative impact on their marriage aspirations. Students indicated that considering a partner’s HIV status prior to marriage was important (p < 0.001), marriage did not offer protection from HIV (p < 0.001), and testing for HIV prior to marriage was imperative (p < 0.001). Considering a partner’s HIV status before marriage is important and associated with increased odds (OR = 5.62, 95%CI: 1.57–20.05) of wanting to get married. There was a significant relationship between respondents wanting to get married and the future marriage partner being HIV negative (p = 0.003). Furthermore, the HIV epidemic has decreased the odds of wanting to get married (OR = 0.21; 95%CI: 0.08–0.58). We conclude that while the majority of young students have marriage aspirations, the high prevalence of HIV has resulted in a negative perception of marriage. Although HIV testing prior to marriage is considered important, students recognize that they may not be protected from infection during marriage.

Stapedo-Vestibular Ankylosis: Retrospective Study of Five Cases in São Tomé e Príncipe

Otosclerosis is a common form of conductive hearing loss characterized by abnormal bone remodeling exclusively in the otic capsule. The prevalence of otosclerosis varies in racial populations and is described as being rare in black African populations. In this paper we aim to report five cases of clinical, and surgically confirmed, otosclerosis in black individuals, in São Tomé and Príncipe. Since February 2011, Ear, Nose and Throat consultations and surgeries specialty have been carried out at Dr. Ayres de Menezes Hospital in cooperation with the project 'Health for all'. A retrospective analysis was undertaken of the records of all patients subjected either to stapedectomy or partial stapedectomy until February 2014. Information regarding clinical presentation, audiometric data and surgery reports was recorded. Five adult patients underwent stapedectomy or partial stapedectomy. All of them presented with normal otoscopy, conductive or mixed hearing loss on audiogram and normal tympanometry with absent stapedial reflexes. None of the patients had signs of infection or history of head trauma. Three cases showed improvement in the air-bone gap after surgery. The other two were lost to follow-up. We documented and surgically confirmed five cases of clinical otosclerosis in this population. A thematic review was carried out and concluded that, despite being described as a rare event in this race, available literature on this topic is not enough to state that there is lower prevalence of otosclerosis amongst the African population. Even if not common, otosclerosis cannot be disregarded as a possible cause for conductive hearing loss among the population of São Tomé and Principe.

Craniofacial manifestations in osteogenesis imperfecta type III in South Africa

Objectives:Osteogenesis imperfecta type III (OMIM 259420) is a severe autosomal recessive disorder. Affected individuals have multiple fractures, develop limb deformities with spinal malalignment and stunted stature.Materials and methods:The frequency of Osteogenesis imperfecta type III (OI III) is relatively high in the indigenous Black African population of South Africa. A review of the literature revealed a paucity of information regarding the craniofacial manifestations of the disorder in this ethnic group. The findings in 64 affected persons are documented.Results:These abnormalities are related to the abnormal bone matrix which results in a deformed skull and dental malocclusion. The physiological process of swallowing may be an aetiological factor in the progressive development of a flattened palate. Mild changes in the shape of the head of the mandibular condyle and a lack of cortical bone on the joint surfaces were observed on cone beam computed tomography (CBCT) images. Affected persons had marked variations in the paranasal sinuses, including sinus hypoplasia and partial opacification. Cranial base anomalies were diagnosed from cephalometric radiographs and lateral skull radiographs. Platybasia and a ‘J’ shaped sella turcica were observed.Conclusion:The craniofacial abnormalities emphasize the importance of a raised level of awareness in terms of dental management and the challenges.

Life after prostate cancer: A systematic literature review and thematic synthesis of the post-treatment experiences of Black African and Black Caribbean men.

Evidence shows that there are significant ethnic variations in prostate cancer prevalence and outcomes. Specifically, Black African and Black Caribbean men may encounter different post-treatment experiences than Caucasian men due to their disproportionately higher risk of being diagnosed with advanced prostate cancer. But to date, no review of these experiences has been undertaken. This review synthesised findings from existing literature on the post-treatment experiences of Black African and Black Caribbean men with prostate cancer and identified pertinent issues which may be useful to inform practice and future research. Seven databases were systematically searched using developed search terms. Four qualitative studies were identified and critically appraised. Findings are summarised under four main themes: symptom experience, healthcare experience, marital and social relationships and coping strategies. Cultural definitions of masculinity influenced the meanings men gave to their post-treatment experiences. While men's experiences of healthcare varied, the provision of professional support to address their post-treatment distress was lacking. Men derived most support from wives, peers and church communities. A culturally sensitive approach which recognises diversity among Black African and Black Caribbean populations and treats individuals within their religious and socio-cultural contexts could potentially improve men's post-treatment experiences. Areas for further research were also identified.

High prevalence of "non-dipping" blood pressure and vascular stiffness in HIV-infected South Africans on antiretrovirals.

BackgroundHIV-infected individuals are at increased risk of tissue inflammation and accelerated vascular aging (‘inflamm-aging’). Abnormal diurnal blood pressure (BP) rhythms such as non-dipping may contribute to an increased risk of cardiovascular and cerebrovascular events in HIV infected individuals. However, little data exists on ambulatory blood pressure (ABP) and measures of vascular stiffness in the black African HIV infected population.MethodsThis is a cross-sectional analysis of otherwise well, HIV infected outpatients on ART for >5 years. Study assessments included: 24hr ABP monitoring, pulse wave velocity (PWV) and central aortic systolic pressure (CASP) using a AtCor Medical Sphygmocor device, fasting lipogram, oral glucose tolerance test, high-sensitivity C-reactive protein (hsCRP) and anthropometric data. Patients completed a questionnaire of autonomic symptoms. CD4+ counts and viral loads were obtained from the National Laboratory results system.ResultsSixty seven black participants were included in the analysis of whom 91% (n = 61) were female with a mean age of 42.2 ± 8.6 years. The median duration on ART was 7.5 years (IQR = 6–10), 84% were virally supressed and the median CD4 count was 529.5cells/mm3 (IQR = 372.0–686.5). The majority (67%) were classified as overweight and 76% had an increased waist circumference, yet only 88% of participants were normotensive. A hsCRP level in the high cardiovascular risk category was found in 68% of participants. The prevalence of non-dipping BP was 65%. Interestingly, there was no association on multivariable analysis between dipping status and traditional risk factors for non-dipping BP, such as: obesity, autonomic dysfunction and older age.ConclusionThis relatively young cross-sectional sample of predominantly normotensive, but overweight black women on effective ART >5 years showed: a high prevalence of non-dipping BP, inflammation and vascular stiffness. Causality cannot be inferred but cardiovascular risk reduction should be emphasized in these patients.

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OBJECTIVES/SPECIFIC AIMS: Prostate cancer is the second most common cancer in the world for men. For reasons still unclear, aggressive PCa disproportionately affects males of African ancestry (MoAA). Incidence and mortality rates are highest in MoAA as they have consistently shown a 2.3–3.0-fold higher risk of mortality compared with Caucasian men. This aggressiveness of PCa may be due to specific biological factors. Studies have established that microRNAs (miRNAs), essential in post-transcriptional gene regulation, are dysregulated in PCa. miR-1207-3p is encoded at the PVT1 gene locus, which is located downstream of MYC on the 8q24 PCa susceptibility locus. The chromosomal region 8q24 is associated with aggressive PCa. Yet miR-1207-3p in PCa in MoAA has never been investigated. Moreover, studies have shown that PVT1/MYC co-operation is a fundamental feature in all cancers with 8q24 amplification and 98% of the 8q24 amplicons contained concurrent amplification of the MYC and PVT1 loci. Moreover, MYC has been linked to PCa aggressiveness, and has been reported to be downstream of androgen receptor (AR) in some PCa. However, the mechanisms regulating c-MYC have never been studied in MoAA. We have recently demonstrated that miR-1207-3p has prognostic value in PCa, and directly binds to the 3′ UTR of Fibronectin type III domain containing 1 (FNDC1) to regulate a novel FNDC1/fibronectin (FN1)/AR pathway upregulated in metastatic PCa. However, the relevance of this novel and clinically significant miR-1207-3p molecular pathway in PCa in MoAA is unknown. Therefore, we hypothesized that miRNA 1207-3p, encoded at the 8q24 PCa susceptibility locus, is a PCa biomarker with clinical applications in MoAA. Our specific aim was to assess the clinical relevance of miR-1207-3p, FNDC1, FN1, AR, and MYC expression in aggressive PCa in a cohort of West African Black males. METHODS/STUDY POPULATION: Consequently, we aimed to determine the expression profile of miRNA-1207-3p, FNDC1, FN1, AR, and MYC in histologically confirmed normal prostate (n=24), benign prostate (n=44) and malignant prostate tissue (n=29) from prostatectomy or transrectal ultrasound-guided biopsies in patients recruited at the University College Hospital, Ibadan, Nigeria, a sub-Saharan Black African population. In total, 17 patients had tumor tissues with Gleason score ≥8. Tissues were collected in compliance with Institutional Ethics Board approved protocols. RNA extraction, cDNA synthesis, and quantitative-PCR were performed to analyze mRNA expression of miRNA-1207-3p, FNDC1, FN1, AR, and MYC. Statistical analysis were performed using SPSS software. All data were analyzed by the 1-way ANOVA test. Tukey post-hoc test was performed to determine the differences in mean expression between normal and tumor prostate tissues. p&lt;0.05 were considered significant. RESULTS/ANTICIPATED RESULTS: We discovered that miR-1207-3p is significantly underexpressed in prostate tumor tissues [0.09±0.02, 95% CI (0.04, 0.136), p=0.000] in comparison with normal prostate tissue in MoAA [0.92±0.15, 95% CI (0.60, 1.244), p=0.000]. This is the first description of miR-1207-3p differential expression in human clinical PCa in MoAA. In contrast, FNDC1 was significantly overexpressed in prostate tumor tissues [21.93±8.21, 95% CI (4.97, 38.89), p=0.003] in comparison with normal prostate tissues in MoAA [1.57±0.45, 95% CI (0.625, 2.51), p=0.003]. The same positive correlation with advanced disease held true for FN1 [tumor: 13.66±3.53, 95% CI (6.38, 20.93), p=0.000; normal: 1.07±0.235, 95% CI (0.58, 1.56), p=0.000], AR [tumor: 20.49±6.74, 95% CI (6.50, 34.48), p=0.000; normal: 0.94±0.20, 95% CI (0.52, 1.36), p=0.000], and c-MYC [tumor: 33.93±8.43, 95% CI (16.53, 51.33), p=0.000; normal: 1.94±0.36, 95% CI (1.18, 2.70)]. The significantly increased mean expression for FNDC1, FN1, AR, and c-MYC in prostate tumor tissues in comparison with normal prostate tissues indicate that their overexpression is associated with increased risk of cancer progression in MoAA. DISCUSSION/SIGNIFICANCE OF IMPACT: These results show that the underexpression of miR-1207-3p and the overexpression of FNDC1, FN1, AR and MYC is associated with aggressive PCa in MoAA. miR-1207-3p, and it molecular target FNDC1, may be useful biomarkers for prognostication of PCa in MoAA.

Skin cancers of the face in an African Black population

Introduction: The aim of this study was to evaluate the frequency and clinico-anatomical features of facial skin cancers in an African Black population.

Racial animosity and political party partisanship in South Africa: the case of the African National Congress and the Black African majority

ABSTRACTAs it is in many countries, racial rhetoric is a feature of South African national government elections. The use of such rhetoric provokes the question, how much is political party support in the country driven by interracial animosities? Using the nationally representative public opinion dataset, the South African Social Attitudes Survey, this article looks at party closeness to the African National Congress (ANC) amongst the black African population. The ANC is one of the oldest and most powerful political parties on the African continent and currently dominates South Africa’s parliamentary government. Constructing four indexes of racial attitudes and behaviours, the article investigates whether partisanship with the ruling party can be predicted by racial animosity. The period under investigation is 2010–2014. Bivariate and multivariate quantitative techniques are employed to test the relationship between ANC partisanship and racial animosity. The results of this investigation show that racial enmity in the country is troublingly widespread. Public opinion analysis, however, found no correlation between racial acrimony and ANC partisanship. Other factors are driving black African identification with the country’s ruling party. The implications of these results for the study for political party support in South Africa are discussed and future avenues of research presented.

A comprehensive association study of apolipoprotein E-C1-C4-C2 gene cluster variation with plasma lipoprotein traits

Apolipoproteins are major determinants of plasma lipoprotein-lipid distribution. Dyslipidemia with elevated level of low-density lipoprotein cholesterol (LDL-C) and decreased level of high-density lipoprotein cholesterol (HDL-C) is associated with increased risk of cardiovascular disease (CVD), which is a major public health problem worldwide. Therefore, unraveling the genetic basis of plasma lipoprotein-lipid traits would provide insight into risk prediction and contribute to the developing of new therapeutic and intervention measures to reduce the CVD burden, which has a public health importance. The objective of this study was to characterize genetic variation in the APOE-C1-C4-C2 gene cluster on chromosome 19q13.32 by resequencing selected individuals from non-Hispanic White (NHW) and African Black populations with extreme lipid profile and then genotyping the identified sequence variants (common tagSNPs and rare variants) along with the HapMap tagSNPs covering the intergenic regions in the entire datasets (623 NHWs, and 788 Blacks) to evaluate their association with major lipid traits. Sequencing of the four apolipoprotein genes along with their hepatic control regions in subjects falling in the upper (47 NHWs, 48 Blacks), and lower (48 NHWs, 47 Blacks) 10th percentile distribution of HDL-C/triglycerides (TG) revealed 230 variants (215 substitution, 15 indels), of which 63 were shared in both populations, 52 were NHW-specific and 115 were Black-specific. A total of 70 variants (65 sequencing-identified, 5 HapMap tagSNPs) in NHWs and 108 variants (103 sequencing-identified, 5 HapMap tagSNPs) in Blacks were successfully genotyped in the entire datasets and were considered for the association analyses. Twenty variants in NHWs and twenty-four variants in Blacks (MAF>1%) showed nominally significant association (P<0.05) with at least one lipid trait. Although the major contribution of the APOE-C1-C4-C2 gene cluster was on LDL-C and apolipoprotein (apo) B, we observed multiple associations with other lipid traits, including TG, HDL-C, and apoA1. In addition to the significant contribution of common variants, rare/less common variants showed significant association with lipid traits. Our findings confirm the significant contribution of APOE-C1-C4-C2 genetic variation in affecting plasma lipid profile in the general population and consequently the CVD risk.

Relationship between estimated cardiovascular disease risk and insulin resistance in a black African population living with HIV: a cross-sectional study from Cameroon

ObjectivesCardiovascular disease (CVD) and metabolic diseases are growing concerns among patients with HIV infection as a consequence of the improving survival of this population. We aimed to assess the relationship...

Rapid RHD Zygosity Determination Using Digital PCR.

Paternal zygosity testing is used for determining homo- or hemizygosity of RHD in pregnancies that are at a risk of hemolytic disease of the fetus and newborn. At present, this is achieved by using real-time PCR or the Rhesus box PCR, which can be difficult to interpret and unreliable, particularly for black African populations. DNA samples extracted from 53 blood donors were analyzed using 2 multiplex reactions for RHD-specific targets against a reference (AGO1)2 to determine gene dosage by digital PCR. Results were compared with serological data, and the correct genotype for 2 discordant results was determined by long-range PCR (LR-PCR), next-generation sequencing, and conventional Sanger sequencing. The results showed clear and reliable determination of RHD zygosity using digital PCR and revealed that 4 samples did not match the serologically predicted genotype. Sanger sequencing and long-range PCR followed by next-generation sequencing revealed that the correct genotypes for samples 729M and 351D, which were serologically typed as R1R2 (DCe/DcE), were R2r' (DcE/dCe) for 729M and R1r″ (DCe/dcE), R0ry (Dce/dCE), or RZr (DCE/dce) for 351D, in concordance with the digital PCR data. Digital PCR provides a highly accurate method to rapidly define blood group zygosity and has clinical application in the analysis of Rh phenotyped or genotyped samples. The vast majority of current blood group genotyping platforms are not designed to define zygosity, and thus, this technique may be used to define paternal RH zygosity in pregnancies that are at a risk of hemolytic disease of the fetus and newborn and can distinguish between homo- and hemizygous RHD-positive individuals.

Abstract 3507: PVT1 exons 4A, 4B, and 9 are overexpressed in aggressive prostate cancer, and PVT1 exon 4B may distinguish between indolent and aggressive prostate cancer

Abstract Aggressive prostate cancer (PCa) disproportionately affects males of African ancestry (MoAA). However, the underlying molecular mechanisms are unclear. Chromosome 8q24 is a PCa susceptibility locus that harbors the PVT1 non-coding gene. We previously demonstrated that PVT1 exon 9 may be involved in aggressive PCa. Moreover, using the most recent full-genome variability panel from the 1000 Genomes project, we recently identified a string of 75 SNPs in a 26-kb region spanning PVT1 exons 4A and 4B as consistently showing the highest level of genetic differentiation between African and non-African populations. However, the expression of PVT1 exons 4A, 4B, and 9 in prostate tissues of MoAA has never been investigated. Our aim was to determine the expression of PVT1 exons 4A, 4B, and 9 in histologically confirmed normal prostate (n=7), benign prostate (n=11) and malignant prostate tissue (n=11) from prostatectomy or transrectal ultrasound-guided biopsies in Nigeria, a sub-Saharan Black African population. Nine patients had tumor tissues with Gleason score ≥ 8. Tissues were collected in compliance with Institutional Ethics Board approved protocols. RNA extraction, cDNA synthesis, and quantitative-PCR were performed to analyze mRNA expression of PVT1 exons 4A, 4B, and 9. There was a statistically significant difference in the relative expression of PVT1 exons 4A (F(2,82)=9.031, p = 0.000), 4B (F(2,82)=5.294, p = 0.007) and 9 (F(2,82)=4.788, p = 0.011) between groups as determined by one-way ANOVA. Tukey posthoc test showed statistically significant differences between relative mean expression of PVT1 exons 4A, 4B and 9 in prostate tumor tissues versus normal prostate tissues: PVT1 exon 4A (prostate tumor: 3.15±0.497, 95% CI [2.13, 4.17]), (benign prostate: 1.74±0.163, 95% CI [1.41,2.07]), and (normal prostate: 1.28±0.141, 95% CI [0.989, 1.57]); PVT1 exon 4B (prostate tumor: 2.217±0.360, 95% CI[1.47, 2.95]), (benign prostate: 1.17±0.176, 95% CI [0.821,1.53]), and (normal prostate: 1.25±0.169, 95% CI [0.900, 1.60]); PVT1 exon 9 (prostate tumor: 1.71±0.190, 95% CI [1.32, 2.10]), (benign prostate: 1.26±0.148, 95% CI [.967,1.57]), and (normal prostate: 0.944±0.151, 95% CI[0.630, 1.25]). Paired t-test showed a significant difference in the expression profile for PVT1 exon 4B in prostate tumors with Gleason score ≥8 (2.98±0.539, 95% CI [1.90,4.06]) as compared to those with Gleason score ≤7 (1.32±0.340, 95% CI [0.645,2.07]) with p =0.009. These results show that overexpression of PVT1 exons 4A, 4B and 9 is characteristic of PCa in MoAA. Further, PVT1 exons 4B and 9 overexpression are specific for PCa, and PVT1 exon 4B may distinguish between indolent and aggressive PCa in MoAA. Citation Format: Akintunde T. Orunmuyi, Adeodat Ilboudo, Olabiyi G. Ogun, Cuong Bach, S A. Adebayo, Ayo A. Salako, E Oluwabunmi Olapade-Olaopa, Olorunseun O. Ogunwobi. PVT1 exons 4A, 4B, and 9 are overexpressed in aggressive prostate cancer, and PVT1 exon 4B may distinguish between indolent and aggressive prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3507. doi:10.1158/1538-7445.AM2017-3507

Killer-cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) class I genetic diversity in four South African populations

Killer-cell Immunoglobulin-like Receptor (KIR) and Human Leukocyte Antigen (HLA) genotypes vary considerably between individuals and populations due to KIR/HLA allelic variation and variable haplotype configurations of KIR. HLA mediate natural killer cell activity by serving as KIR ligands. KIR/HLA polymorphisms associate with both disease susceptibility and severity. We determined the frequencies of KIR, KIR genotypes and KIR-HLA combinations in 364 healthy individuals from four South African populations. Study participants included black African (n=167), Caucasian (n=97), Mixed ancestry (n=50) and Indian (n=50) individuals. We identified 48 KIR genotypes that included two genotypes not previously reported. Based on KIR gene content, Indian individuals represented the most distinct group, showing the highest frequencies of KIR2DL2, KIR2DL5, KIR2DS1, KIR2DS2, KIR2DS3 and KIR3DS1, the lowest frequencies of KIR2DL3, KIR2DS4 and KIR3DL1; and a KIR2DL4-negative individual. KIR2DS1 and KIR3DS1 were infrequent in black African populations. HLA-C2 was more common in black African individuals, while HLA-C1 predominated in the other populations. Indian individuals were more likely to possess KIR2DL2 paired with HLA-C1, while Caucasian individuals exhibited the highest frequencies of KIR2DL3 paired with HLA-C1. This report provides comprehensive reference data for further study of the roles of KIR/HLA in non-communicable and infectious diseases in South African populations.

Can we do more with HIV testing?

In 2015 an estimated 0.8% of adults aged 15–49 years worldwide are living with HIV infection, although the rates have been variable between countries and regions (www.who.int/gho/hiv/en/). Rates in Europe have been estimated to be around 0.4%. The diagnosed HIV prevalence rate in London in 2015 was 5.8 per 1000 residents aged 15–59 years ( https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/594779/London_HIV_Spotlight_2015_data.pdf), but the rates were much higher (~27%) in Black African populations than in the White population (~5%). A number of initiatives were introduced in Europe over the last decade to help with the early diagnosis of HIV in people unaware of their HIV infection. One such initiative was ‘indicator condition-guided HIV testing’, which recommended the routine offer of HIV testing at the first diagnosis of an indicator disease such as cervical dysplasia, and was based on the prevalence rates or assumed rates of >0.1% of HIV infection (Lazarus et al. HIV Medicine 2013;14:445–8). Using population-based register linked data, Carlander et al. show the prevalence rates of undiagnosed HIV to be 0.3% in migrant women with cervical intraepithelial neoplasia grade 2+ (CIN2+) diagnoses, and argue that HIV testing should be performed in migrant women with CIN2+ disease and with unknown HIV status. Most will agree with this conclusion, but many will go beyond. Their data also show the rate of undiagnosed HIV to be 0.08% in migrant women without CIN2+ diagnosis, and some of the migrant subgroups without CIN2+ exceeded 0.1% prevalence. A more equitable approach will be to offer HIV testing to all migrant women with any cervical abnormality or to those referred for colposcopy. One may argue that in places with population HIV prevalence rates of >0.1%, as in London, HIV testing should be made available to all those who present with cervical dysplasia. Immune suppression leads to adverse outcomes of treatment of CIN2+ disease. The data presented by Carlander et al. is notable for a second reason. The median CD4 nadir measurements in their cohort was in the range of 25–310 cells/μL amongst women with CIN2+ diagnoses, and 122–260 cells/μL in all other women without CIN2+ diagnoses. Late presentation (CD4 < 350 cells/μL) in HIV is associated with increased morbidity and mortality. Initiating HIV antiretroviral treatment when CD4 measurements are >500 cells/μL leads to a reduction in serious health events and deaths when compared with starting HIV treatment at CD4 counts of 350 cells/μL or below (The INSIGHT START Study Group N Engl J Med 2015;373:795–807). Offering HIV testing to all women will help to prevent late presentations. A number of factors such as the duration of undiagnosed HIV, its transmissibility to others, and healthcare costs of late diagnosis need consideration against the costs of testing. We now have several types of HIV tests that can enable better access to testing. In immune-suppressed women, HPV-related multizonal anogenital neoplasia and cancers are more common, and may continue to manifest long after cervical disease. The earlier the diagnosis and treatment of HIV, the better are the chances of prevention of malignant disease in the lower anogenital tract. None declared. Completed disclosure of interests form available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Differences in Sleep Duration among Four Different Population Groups of Older Adults in South Africa.

The study aims to investigate sleep duration in four different population groups in a national probability sample of older South Africans who participated in the Study of Global Ageing and Adult Health (SAGE) Wave 1. A national population-based cross-sectional study with a sample of 3284 aged 50 years or older in South Africa was conducted in 2008. The questionnaire included socio-demographic characteristics, health variables, and self-reported sleep duration. Results indicate that White Africans compared to other population groups had the lowest mean sleep duration (7.88 h among men and 7.46 h among women). The prevalence of short sleep was the highest among both men and women among the White African (18.8% in men and 16.9% in women) and Indian or Asian African population groups (14.5% in men and 17.1% in women), and lowest among both men and women in the Black African (7.0% in men and 6.5% in women) and multi-ancestry population groups (15.6% in men and 12.7% in women). The prevalence of long sleep was among both men and women the highest in the Black African population group (56.2% in men and 58.5% in women), and the lowest in the White African population group (36.4% in men and 24.3% in women). In a Poisson regression model, adjusted for sociodemographics and chronic disease status, coming from the male and female White African population group was associated with short sleep. In addition, coming from the Indian or Asian African population group was associated with short sleep. No population group differences were found regarding long sleep prevalence. White Africans reported more short sleep duration than the other population groups, while there were no racial or ethnic differences in long sleep. White Africans are more likely to have sleep durations that are associated with negative health outcomes. An explanation of the high short sleep prevalence among White Africans may be related to their racial or ethnic minority status in South Africa.

Osteogenesis imperfecta type 3 in South Africa: Causative mutations in FKBP10.

A relatively high frequency of autosomal recessively inherited osteogenesis imperfecta (OI) type 3 (OI-3) is present in the indigenous black southern African population. Affected persons may be severely handicapped as a result of frequent fractures, progressive deformity of the tubular bones and spinal malalignment. To delineate the molecular basis for the condition. Molecular investigations were performed on 91 affected persons from seven diverse ethnolinguistic groups in this population. Following polymerase chain reaction amplification and direct cycle sequencing, FKBP10 mutations were identified in 45.1% (41/91) OI-3-affected persons. The homozygous FKBP10 c.831dupC frameshift mutation was confirmed in 35 affected individuals in the study cohort. Haplotype analysis suggests that this mutation is identical among these OI-3-affected persons by descent, thereby confirming that they had a common ancestor. Compound heterozygosity of this founder mutation was observed, in combination with three different deleterious FKBP10 mutations, in six additional persons in the cohort. Four of these individuals had the c.831delC mutation. The burden of the disorder, both in frequency and severity, warrants the establishment of a dedicated service for molecular diagnostic confirmation and genetic management of persons and families with OI in southern Africa.

The challenge of acute coronary syndromes in South Africa

Atherosclerotic coronary artery disease remains highly prevalent in South Africa. Whereas in the past the disease predominantly affected the white and Indian population groups, there is a slow but steady rise in the prevalence of coronary artery disease in the black African population.