Browsing by Author "Bates, William"

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    African KhoeSan ancestry linked to high-risk prostate cancer
    (BMC (part of Springer Nature), 2019-06-04) Petersen, Desiree C.; Jaratlerdsiri, Weerachai; Van Wyk, Abraham; Chan, Eva K. F.; Fernandez, Pedro; Lyons, Ruth J.; Mutambirw, Shingai B. A.; Van der Merwe, Andre; Venter, Philip A.; Bates, William; Bornman, M. S. R.; Hayes, Vanessa M.
    Backgrounds: Genetic diversity is greatest within Africa, in particular the KhoeSan click-speaking peoples of southern Africa. South African populations represent admixture fractions including differing degrees of African, African-KhoeSan and non-African genetic ancestries. Within the United States, African ancestry has been linked to prostate cancer presentation and mortality. Together with environmental contributions, genetics is a significant risk factor for high-risk prostate cancer, defined by a pathological Gleason score ≥ 8. Methods: Using genotype array data merged with ancestry informative reference data, we investigate the contribution of African ancestral fractions to high-risk prostate cancer. Our study includes 152 South African men of African (Black) or African-admixed (Coloured) ancestries, in which 40% showed high-risk prostate cancer. Results: Genetic fractions were determined for averaging an equal African to non-African genetic ancestral contribution in the Coloured; we found African ancestry to be linked to high-risk prostate cancer (P-value = 0.0477). Adjusting for age, the associated African ancestral fraction was driven by a significant KhoeSan over Bantu contribution, defined by Gleason score ≥ 8 (P-value = 0.02329) or prostate specific antigen levels ≥20 ng/ml (Pvalue = 0.03713). Additionally, we observed the mean overall KhoeSan contribution to be increased in Black patients with high-risk (11.8%) over low-risk (10.9%) disease. Linking for the first time KhoeSan ancestry to a common modern disease, namely high-risk prostate cancer, we tested in this small study the validity of using KhoeSan ancestry as a surrogate for identifying potential high-risk prostate cancer risk loci. As such, we identified four loci within chromosomal regions 2p11.2, 3p14, 8q23 and 22q13.2 (P-value = all age-adjusted < 0.01), two of which have previously been associated with high-risk prostate cancer. Conclusions: Our study suggests that ancient KhoeSan ancestry may be linked to common modern diseases, specifically those of late onset and therefore unlikely to have undergone exclusive selective pressure. As such we show within a uniquely admixed South African population a link between KhoeSan ancestry and high-risk prostate cancer, which may explain the 2-fold increase in presentation in Black South Africans compared with African Americans.
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    Pattern of renal amyloidosis in South Africa
    (BMC (part of Springer Nature), 2019) Hassen, Muhammed; Bates, William; Moosa, Mohammed Rafique
    Background: Kidney disease is a serious manifestation of systemic amyloidosis and a major cause of morbidity and mortality. Tuberculosis (TB) occurs up to 27 times more commonly in human immunodeficiency virus (HIV) infected patients and is also an important cause of renal amyloid; there are however no reports of renal amyloidosis in South Africa in the HIV era. Methods: This was a retrospective record review of cases of amyloidosis diagnosed on renal biopsies at our tertiary referral hospital between January 1985 and December 2016. Results: Forty-six cases of amyloidosis were identified over the study period. The calculated biopsy prevalence was 1.38 per 100 non-transplant renal biopsies (95% Confidence Interval 1.02–1.86). AL amyloidosis was identified in 26 (57%) cases and AA in 20 (43%). The median age at presentation was 51 years and 52% of cases were female. Patients with AA amyloidosis were significantly younger compared to their AL counterparts (age 42 years vs. 58 years, p = < 0.001) and were all significantly non-white. The main clinical presentation was nephrotic syndrome (85%) and 52% of cases also had a serum creatinine value of greater than 120 μmol/L. Of the 20 cases of AA amyloidosis, 12 (60%) were associated with tuberculosis. HIV infection was noted in only two (10%) of the 20 AA cases. Median survival after diagnosis was 2 months. Conclusion: Amyloidosis is a rare cause of kidney disease and typically presents with nephrotic syndrome. A similar number of AA and AL types were observed, and outcomes are worse in cases of AA amyloid. While TB remains the major underlying disease in this type, HIV infection was infrequent in cases of AA renal amyloidosis.