Ethical, Legal and Social Issues of Genetic Studies with African Immigrants as Research Subjects

Gong, Gordon; Kosoko-Lasaki, Sade; Haynatzki, Gleb; Cook, Cynthia A. Loveland; O’Brien, Richard L.; Houtz, Lynne E.

doi:10.1016/s0027-9684(15)31447-4

Cited by 7 publications

(8 citation statements)

References 20 publications

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“…The protein is also present in aqueous humor (9,10). Interestingly, most MYOC mutations reported to date in sporadic cases of primary open angle glaucoma are heterozygous and are confined to exon 3 (2,5,6,(11)(12)(13). Recently, we showed that myocilin undergoes an intracellular endoproteolytic cleavage in the endoplasmic reticulum (ER) between amino acids Arg 226 and Ile 227 located in the putative linker domain (10).…”

mentioning

confidence: 99%

Characterization of the Intracellular Proteolytic Cleavage of Myocilin and Identification of Calpain II as a Myocilin-processing Protease

Sánchez-Sánchez

Martínez-Redondo

Aroca-Aguilar

et al. 2007

Journal of Biological Chemistry

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MYOC, a gene involved in different types of glaucoma, encodes myocilin, a secreted glycoprotein of unknown function, consisting of an N-terminal leucine-zipper-like domain, a central linker region, and a C-terminal olfactomedin-like domain. Recently, we have shown that myocilin undergoes an intracellular endoproteolytic processing. We show herein that the proteolytic cleavage in the linker region splits the two terminal domains. The C-terminal domain is secreted to the culture medium, whereas the N-terminal domain mainly remains intracellularly retained. In transiently transfected 293T cells, the cleavage was prevented by calpain inhibitors, such as calpeptin, calpain inhibitor IV, and calpastatin. Since calpains are calciumactivated proteases, we analyzed how changes in either intra-or extracellular calcium affected the cleavage of myocilin. Intracellular ionomycin-induced calcium uptake enhanced myocilin cleavage, whereas chelation of extracellular calcium by EGTA inhibited the proteolytic processing. Calpains I and II cleaved myocilin in vitro. However, in cells in culture, only RNA interference knockdown of calpain II reduced myocilin processing. Subcellular fractionation and digestion of the obtained fractions with proteinase K showed that full-length myocilin resides in the lumen of the endoplasmic reticulum together with a subpopulation of calpain II. These data revealed that calpain II is responsible for the intracellular processing of myocilin in the lumen of the endoplasmic reticulum. We propose that this cleavage might regulate extracellular interactions of myocilin, contributing to the control of intraocular pressure.

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confidence: 99%

Characterization of the Intracellular Proteolytic Cleavage of Myocilin and Identification of Calpain II as a Myocilin-processing Protease

Sánchez-Sánchez

Martínez-Redondo

Aroca-Aguilar

et al. 2007

Journal of Biological Chemistry

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“…‘They believed that genetic discoveries might pin diseases to particular groups, producing ‘blanket discrimination' and ‘racial profiling'' [[21],p199]. If geneticists lack an appreciation of indigenous African ideologies and practices, this will likely interfere with opportunities for this population's participation in genomic research [25,26]. The health beliefs, historical injustices and sociocultural influences, as they intersect with perspectives on genetic testing and willingness to participate in genetic initiatives, deserve exploration and investigation in future research with Black African immigrants/refugees.…”

Section: Discussionmentioning

confidence: 99%

Knowledge, Group-Based Medical Mistrust, Future Expectations, and Perceived Disadvantages of Medical Genetic Testing: Perspectives of Black African Immigrants/Refugees

Buseh¹,

Kelber²,

Millon‐Underwood³

et al. 2013

Public Health Genomics

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Background: Reasons for low participation of ethnic minorities in genetic studies are multifactorial and often poorly understood. Based on published literature, participation in genetic testing is low among Black African immigrants/refugees although they are purported to bear disproportionate disease burden. Thus, research involving Black African immigrant/refugee populations that examine their perspectives on participating in genetic studies is needed. Objectives: This report examines and describes the knowledge of medical genetics, group-based medical mistrust, and future expectations of genetic research and the influence of these measures on the perceived disadvantages of genetic testing among Black African immigrants/refugees. Methods: Using a cross-sectional survey design, a nonprobability sample (n = 212) of Black African immigrants/refugees was administered a questionnaire. Participants ranged in age from 18 to 61 years (mean = 38.91, SD = 9.78). The questionnaire consisted of 5 instruments: (a) sociodemographic characteristics, (b) Knowledge of Medical Genetics scale, (c) Group-Based Medical Mistrust Scale, (d) Future Expectations/Anticipated Consequences of Genetics Research scale, and (e) Perceived Disadvantages of Genetic Testing scale. Results: Participants were concerned that genetic research may result in scientists ‘playing God,' interfering with the natural order of life. In multivariate analyses, the perceived disadvantages of genetic testing increased as medical mistrust and anticipated negative impacts of genetic testing increased. Increase in genetic knowledge contributed to a decrease in perceived disadvantages. Conclusions: Our findings suggest that recruitment of Black African immigrants/refugees in genetic studies should address potential low knowledge of genetics, concerns about medical mistrust, the expectations/anticipated consequences of genetic research, and the perceived disadvantages of genetic testing.

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“…The legacy of colonialism is difficult to disentangle from the experience of RT, especially when the destination country is a former European colony, such as India. Perspectives from Africa suggest that illiteracy and a colonial heritage combine to make informed consent problematic 15. The same forces apply in India, where an authority figure modelled on an image of Western power, such as a doctor, is afforded automatic deference.…”

Section: Discussionmentioning

confidence: 99%

Ethical concerns for maternal surrogacy and reproductive tourism

2012

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Reproductive medical tourism is by some accounts a multibillion dollar industry globally. The seeking by clients in high income nations of surrogate mothers in low income nations, particularly India, presents a set of largely unexamined ethical challenges. In this paper, eight such challenges are elucidated to spur discussion and eventual policy development towards protecting the rights and health of vulnerable women of the Global South.

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Ethical, Legal and Social Issues of Genetic Studies with African Immigrants as Research Subjects

Cited by 7 publications

References 20 publications

Characterization of the Intracellular Proteolytic Cleavage of Myocilin and Identification of Calpain II as a Myocilin-processing Protease

Characterization of the Intracellular Proteolytic Cleavage of Myocilin and Identification of Calpain II as a Myocilin-processing Protease

Knowledge, Group-Based Medical Mistrust, Future Expectations, and Perceived Disadvantages of Medical Genetic Testing: Perspectives of Black African Immigrants/Refugees

Ethical concerns for maternal surrogacy and reproductive tourism

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