Counseling Persons of Black African Ancestry

Plasmodium vivax malaria is endemic in Mauritania. Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency may develop acute hemolytic anemia when exposed to 8-aminoquinoline antimalarial drugs, which are indispensable for a complete cure. The prevalence of G6PD allelic variants was assessed in different ethno-linguistic groups present in Mauritania. A total of 996 blood samples (447 males and 549 females; 499 white Moors and 497 individuals of black African ancestry) were collected from febrile patients in 6 different study sites: Aleg, Atar, Kiffa, Kobeni, Nouakchott, and Rosso. The presence of the African-type G6PD A- (G202A, A376G, A542T, G680T, and T968C mutations) and the Mediterranean-type G6PD B- (C563T) variants was assessed by PCR followed by restriction fragment length polymorphism and/or DNA sequencing. The prevalence of African-type G6PD A- genotype was 3.6% (36/996), with 6.3% (28/447) of hemizygote (A-) males and 1.5% (8/549) of homozygous (A-A-) females. Forty of 549 (7.3%) women were heterozygous (AA-). The following genotypes were observed among hemizygous men and/or homozygous women: A376G/G202A (22/996; 2.2%), A376G/T968C Betica-Selma (12/996; 1.2%), and A376G/A542T Santamaria (2/996; 0.2%). The Mediterranean-type G6PD B- genotype was not observed. The prevalence rates of G6PD A- genotype in male (10/243; 4.1%) and heterozygous female (6/256; 2.3%) white Moors were lower (p < 0.05) than those of males (18/204; 8.8%) and heterozygous females (34/293; 11.6%) of black African ancestry. There were only a few homozygous women among both white Moors (3/256; 1.2%) and those of black African ancestry (5/293; 1.7%). The prevalence of G6PD deficiency in Mauritania was comparable to that of neighboring countries in the Maghreb. Because of the purportedly close ethnic ties between the Mauritanian white Moors and the peoples in the Maghreb, further investigations on the possible existence of the Mediterranean-type allele are required. Moreover, a surveillance system of G6PD phenotype and/or genotype screening is warranted to establish and monitor a population-based prevalence of G6PD deficiency.

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Application of the Optimized Summed Score Attributes Method for Sex Estimation

Forensic Anthropology ◽

10.5744/fa.2020.0049 ◽

2021 ◽

Author(s):

Holly Long ◽

Alexandra Klales

Keyword(s):

Sexual Dimorphism ◽

African Ancestry ◽

European Ancestry ◽

Sex Bias ◽

Sex Estimation ◽

Black African ◽

Asian Populations ◽

Novel Approach ◽

Calibration Sample ◽

Accuracy Rates

The optimized summed scored attributes (OSSA) method was first developed for cranial ancestry estimation (Hefner & Ousley 2014). Tallman and Go (2018) adapted this method for sex estimation with the five skull traits described by Buikstra and Ubelaker (1994) and Walker (2008). Using an Asian sample, Tallman and Go (2018) achieved moderate accuracy rates (83.7% calibration; 81.9% validation) but also high sex bias (29.1% calibration; 34.5% validation), possibly due to lower levels of sexual dimorphism in Asian populations. To further explore this novel approach to sex estimation, the OSSA method was applied to a U.S. Black/African ancestry and White/European ancestry calibration sample (N = 700). Accuracy rates were 77.4% in Black individuals and 77.2% in White individuals. Despite generally higher levels of sexual dimorphism in these groups, a high sex bias still occurred (15.4% Black individuals; –20.5% White individuals) using OSSA. The method was tested in a separate validation sample (N = 200) with accuracy of 78.0% in Black individuals (8.0% sex bias) and 70.0% in White individuals (–56.0% sex bias). When these same traits were tested with Walker’s (2008) logistic regression and in the MorphoPASSE Program (Klales 2018) using random forest modeling, accuracy rates varied ,with OSSA (77.3% correct), performing slightly better than Walker’s (2008) method (75.6% correct) but worse than MorphoPASSE (85.3% correct). The higher accuracy and lower sex bias in MorphoPASSE suggests that the Walker (2008) traits can be used to accurately estimate sex with statistical approaches more appropriate and robust than OSSA.

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Neutralizing and Non-Neutralizing Anti-FVIII Antibodies in Black and White Hemophilia A Subjects: A Natural History Profile

Blood ◽

10.1182/blood-2019-124743 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1131-1131 ◽

Cited By ~ 1

Author(s):

Kathleen P. Pratt ◽

Devi Gunasekera ◽

Pooja Vir ◽

Robert Peters ◽

Siyuan Tan ◽

...

Keyword(s):

B Cell ◽

Hemophilia A ◽

African Ancestry ◽

Full Length ◽

Inhibitory Antibody ◽

B Cell Epitopes ◽

Black African ◽

Coagulation Inhibitors ◽

Antibody Titers ◽

Linear B

The most common complication in hemophilia A (HA) treatment, affecting 25-30% of severe HA patients, is the development of alloimmune inhibitors that foreclose the ability of infused factor VIII (FVIII) to participate in coagulation. Inhibitors confer significant pathology on affected individuals and present major complexities in their management. Inhibitors are more common in African American patients, and it has been hypothesized that this is a consequence of haplotype (H)-treatment product mismatch. F8 gene haplotypes H1-H5 are defined by combinations of nonsynonymous SNPs encoding FVIII sequence variants D1241E, M2238V and R484H. F8 haplotypes H2-H5 are more prevalent in individuals with black African ancestry, while >90% of the white population has the H1 haplotype. This study used a validated Luminex-based assay to determine total anti-FVIII antibody titers in plasma from 395 HA (189 black, 206 white) and 23 non-HA control subjects, measuring their binding to recombinant full-length H1 and H2 and B-domain-deleted (BDD) H1/H2, H3 and H4 FVIII proteins. Inhibitor titers were determined using a chromogenic Bethesda assay with the Nijmegen modification. Linear B-cell epitopes recognized by antibodies in human plasma samples were characterized using commercial peptide microarrays with imprinted 15-mer peptides spanning the FVIII A1, A2, C1 and C2 domains, with binding interactions detected using fluorescent-labeled anti-human IgG antibodies. Neither total nor inhibitory antibody titers correlated with F8 haplotype. FVIII peptides with the D1241E and M3348V polymorphisms showed low antibody reactivity, indicating they do not comprise linear B-cell epitopes. Similarly, antibodies from subjects with H3 and H5 haplotypes, who were necessarily infused with FVIII products having a different haplotype than that of their endogenous, (dysfunctional) F8 sequence, did not show haplotype-correlated differential binding to the three BDD-FVIII or full-length FVIII proteins, indicating the polymorphic M2238V or D1241E sites do not correspond to immunodominant, conformational B-cell epitopes. Interestingly, the BDD-FVIII proteins were significantly more reactive with antibodies in plasma than were two commercial full-length recombinant FVIII products. Overall, results of this study indicated that low-titer FVIII-reactive antibodies are readily detected in most HA subjects and in a majority of healthy non-HA controls. The observed stronger immunoreactivity of BDD-FVIII suggests that B-domain removal exposes novel B-cell epitopes, perhaps through conformational rearrangements of FVIII domains. Disclosures Pratt: Bloodworks NW: Patents & Royalties: inventor on patents related to FVIII immunogenicity; Grifols, Inc: Research Funding. Peters:Sanofi: Employment. Mann:Haematologic Technologies: Other: Owner; Stago: Consultancy; Novo Nordisk: Consultancy; Takeda: Consultancy; Shire: Consultancy; Baxalta: Consultancy.

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Ectopic fat deposition in populations of black African ancestry: A systematic review and meta-analysis

Acta Diabetologica ◽

10.1007/s00592-021-01797-5 ◽

2021 ◽

Author(s):

Reuben M. Reed ◽

Sarah J. Nevitt ◽

Graham J. Kemp ◽

Daniel J. Cuthbertson ◽

Martin B. Whyte ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

African Ancestry ◽

European Ancestry ◽

Ectopic Fat ◽

Potential Contribution ◽

Black African ◽

Fat Depots ◽

Ectopic Fat Deposition ◽

Intrahepatic Lipid

Abstract Aims In populations of black African ancestry (BA), a paradox exists whereby lower visceral adipose tissue is found despite their high risk for type 2 diabetes (T2D). This systematic review investigates ethnic differences in other ectopic fat depots (intrahepatic lipid: IHL; intramyocellular lipid: IMCL and intrapancreatic lipid; IPL) to help contextualise their potential contribution to T2D risk. Methods A systematic literature search was performed in December 2020 to identify studies reporting at least one ectopic fat comparison between BA and one/more other ethnicity. For IHL, a meta-analysis was carried out with studies considered comparable based on the method of measurement. Results Twenty-eight studies were included (IHL: n = 20; IMCL: n = 8; IPL: n = 4). Meta-analysis of 11 studies investigating IHL revealed that it was lower in BA populations vs pooled ethnic comparators (MD −1.35%, 95% CI −1.55 to −1.16, I2 = 85%, P < 0.00001), white European ancestry (MD −0.94%, 95% CI −1.17 to -0.70, I2 = 79%, P < 0.00001), Hispanic ancestry (MD −2.06%, 95% CI −2.49 to −1.63, I2 = 81%, P < 0.00001) and South Asian ancestry comparators (MD −1.92%, 95% CI −3.26 to −0.57, I2 = 78%, P = 0.005). However, heterogeneity was high in all analyses. Most studies found no significant differences in IMCL between BA and WE. Few studies investigated IPL, however, indicated that IPL is lower in BA compared to WE and HIS. Conclusion The discordance between ectopic fat and greater risk for T2D in BA populations raises questions around its contribution to T2D pathophysiology in BA.

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