scholarly journals The Genetic Contribution of West-African Ancestry to Protection against Central Obesity in African-American Men but Not Women: Results from the ARIC and MESA Studies

2016 ◽  
Vol 7 ◽  
Author(s):  
Yann C. Klimentidis ◽  
Amit Arora ◽  
Jin Zhou ◽  
Rick Kittles ◽  
David B. Allison
Keyword(s):  
African American ◽  
Central Obesity ◽  
African American Men ◽  
African Ancestry ◽  
West African ◽  
Genetic Contribution ◽  
West African Ancestry

scholarly journals Enrichment for Cases of African-American Patients with Pathogenic TTR V142I Variant in the TOPCAT Trial

2020 ◽  
Author(s):  
Nikolaos Papoutsidakis ◽  
Neeru Gandotra ◽  
Edward Miller ◽  
Michael F. Murray ◽  
Curt Scharfe ◽  
...  
Keyword(s):  
Heart Failure ◽  
African American ◽  
High Frequency ◽  
Clinical Utility ◽  
African Ancestry ◽  
West African ◽  
Non Invasive ◽  
The Past ◽  
Diagnostic Approaches ◽  
West African Ancestry

AbstractTransthyretin cardiac amyloidosis (ATTR-CA) is a treatable cause of heart failure with a hereditary form that disproportionally affects patients of West African ancestry. The clinical management of ATTR-CA has dramatically changed in the past five years, with rapidly evolving diagnostic approaches and life-prolonging therapies. The TTR variant c.424G>A, p.V142I (aka V122I) is pathogenic and occurs in 3-4% of individuals of West African ancestry. Despite its high frequency, V142I ATTR-CA is often unrecognized due to variable clinical penetrance, limited knowledge, and lack of inexpensive non-invasive diagnostic tests. Currently unknown is which TTR V142I carriers will progress to heart failure and at what age. Here we studied the prevalence of TTR V142I among a random cohort of African-American patients enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial (TOPCAT). Three of the 26 HFpEF patients (11.5%) studied carried the pathogenic TTR V142I variant. While we cannot conclude at this point that TTR V142I was the underlying cause of the clinical phenotype in these patients, our results suggest that rapid TTR V142I genotyping, in combination with heart imaging, could have immediate clinical utility for identifying under-/mis-diagnosed HFpEF patients.

scholarly journals Methionine-Homocysteine Pathway in African-American Prostate Cancer

2019 ◽  
Vol 3 (2) ◽  
Author(s):  
Jie H Gohlke ◽  
Stacy M Lloyd ◽  
Sumanta Basu ◽  
Vasanta Putluri ◽  
Shaiju K Vareed ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Molecular Mechanisms ◽  
Statistical Tests ◽  
African Ancestry ◽  
Tumor Biology ◽  
West African ◽  
Self Report ◽  
European American ◽  
West African Ancestry

Abstract African American (AA) men have a 60% higher incidence and two times greater risk of dying of prostate cancer (PCa) than European American men, yet there is limited insight into the molecular mechanisms driving this difference. To our knowledge, metabolic alterations, a cancer-associated hallmark, have not been reported in AA PCa, despite their importance in tumor biology. Therefore, we measured 190 metabolites across ancestry-verified AA PCa/benign adjacent tissue pairs (n = 33 each) and identified alterations in the methionine-homocysteine pathway utilizing two-sided statistical tests for all comparisons. Consistent with this finding, methionine and homocysteine were elevated in plasma from AA PCa patients using case-control (AA PCa vs AA control, methionine: P = .0007 and homocysteine: P < .0001), biopsy cohorts (AA biopsy positive vs AA biopsy negative, methionine: P = .0002 and homocysteine: P < .0001), and race assignments based on either self-report (AA PCa vs European American PCa, methionine: P = .001, homocysteine: P < .0001) or West African ancestry (upper tertile vs middle tertile, homocysteine: P < .0001; upper tertile vs low tertile, homocysteine: P = .002). These findings demonstrate reprogrammed metabolism in AA PCa patients and provide a potential biological basis for PCa disparities.

scholarly journals Serum proteomics links suppression of tumor immunity to ancestry and lethal prostate cancer

2021 ◽  
Author(s):  
Tsion Minas ◽  
Julián Candia ◽  
Tiffany Dorsey ◽  
Francine Baker ◽  
Wei Tang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Tumor Immunity ◽  
African American Men ◽  
African Ancestry ◽  
European American ◽  
Serum Proteomics ◽  
Immune Oncology ◽  
Lethal Prostate Cancer ◽  
West African Ancestry

Abstract There is evidence that tumor immunobiology and immunotherapy response may differ between African American and European American prostate cancer patients. Here, we determined if men of African descent harbor a unique systemic immune-oncological signature and measured 82 circulating proteins in almost 3000 Ghanaian, African American, and European American men. Protein signatures for suppression of tumor immunity and chemotaxis were significantly elevated in men of West African ancestry. Importantly, the suppression of tumor immunity protein signature associated with metastatic and lethal prostate cancer, pointing to clinical significance. Moreover, two markers, pleiotrophin and TNFRSF9, predicted poor disease survival specifically among African American men. These findings indicate that immune-oncology marker profiles differ between men of African and European descent. These differences may contribute to the disproportionate burden of lethal prostate cancer in men of African ancestry. The elevated peripheral suppression of tumor immunity may have important implication for guidance of cancer therapy which could particularly benefit African American patients.

scholarly journals Prevalence of HIV/hepatitis B and HIV/hepatitis C coinfection among people of East, South, Central and West African ancestry in the United Kingdom

AIDS ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Rachel Hung ◽  
Nisha Patel ◽  
Julie Fox ◽  
Catherine Cosgrove ◽  
Sarah L. Pett ◽  
...  
Keyword(s):  
United Kingdom ◽  
Hepatitis C ◽  
Hepatitis B ◽  
African Ancestry ◽  
West African ◽  
The United Kingdom ◽  
South Central ◽  
West African Ancestry

Abstract 3516: Commercial gene expression tests for prostate cancer outcome risk in men of West African ancestry

2020 ◽  
Author(s):  
Sandra M. Gaston ◽  
Rick A. Kittles ◽  
Radka Stoyanova ◽  
Teresa M. Giret ◽  
Saba A. Ansari ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
African Ancestry ◽  
West African ◽  
Cancer Outcome ◽  
West African Ancestry

scholarly journals Vitamin D deficiency increases prostatic megalin expression and globulin-bound testosterone import, increasing prostatic androgens in African American men

2021 ◽  
Author(s):  
Jason Garcia ◽  
Kirsten Krieger ◽  
Candice Loitz ◽  
Lillian M Perez ◽  
Zachary A Richards ◽  
...  
Keyword(s):  
Vitamin D ◽  
African American ◽  
African Americans ◽  
Vitamin D Deficiency ◽  
African American Men ◽  
African Ancestry ◽  
Serum Vitamin ◽  
Vitamin D Metabolites ◽  
Increased Risk ◽  
Vitamin D Levels

Vitamin D deficiency associates with an increased risk of prostate cancer (PCa) mortality and is hypothesized to contribute to PCa aggressiveness and disparities in African Americans. We reported a relationship between African-ancestry, circulating and intraprostatic vitamin D metabolites and prostatic expression of megalin, an endocytic membrane receptor that internalizes globulin-bound hormones. Here, we show that megalin imports sex hormone-binding globulin (SHBG)-bound testosterone, potentially regulating intraprostatic hormone levels. Vitamin D levels regulated megalin expression in cell lines, patient-derived prostate epithelial cells, and prostate tissue explants, and mice with prostatic knockout of Lrp2 (megalin) showed reduced prostatic testosterone. Notably, prostatic 5α-dihydrotestosterone levels were higher in African American men and correlated inversely with serum vitamin D status, while megalin protein levels were reduced in PCa tissue. Our findings highlight the negative impact of vitamin D deficiency on PCa and the potential link to PCa disparities observed in African Americans.

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