Ethical, legal and social issues of genetic studies with African immigrants as research subjects.

There is growing interest in exploring gene-environment interactions in the etiology of diseases in immigrants from sub-Saharan Africa. Our experience working with the Sudanese immigrant population in Omaha, NE, makes clear the pressing need for geneticists and federal and local funding agencies to address the ethical, legal and social implications of genetic research with such vulnerable populations. Our work raises several questions. How does one design research with African immigrant participants to assure it is ethical? Many immigrants may not understand the purposes, risks and benefits involved in research because of low literacy rates, one of the results of civil wars, or concepts of biologic science foreign to their cultures. Is it possible to obtain truly informed consent? Do African immigrants perceive genetic research using them as subjects as racist? Is genetic research on minorities "biopiracy" or "bio-colonialism?" In our experience, some Sudanese immigrants have challenged the legality and ethics of genetic studies with profit-making as an end. We have concluded that it is essential to educate African immigrant or any other non-English-speaking immigrant participants in research using lay language and graphic illustrations before obtaining consent. Cultural proficiency is important in gaining the trust of African immigrants; profit-sharing may encourage their participation in genetic research to benefit all; involvement of African immigrant community leaders in planning, delivery and evaluation using the community-based participatory research approach will facilitate healthcare promotion, health literacy education, as well as genetic research. It is crucial to address the ethical, legal and social implications of genetic studies with African immigrants as research subjects.

Inherited, familial and sporadic primary open-angle glaucoma.

UNLABELLED: The U.S. surgeon general has recently launched a campaign to promote the awareness of the medical value of family history. Further attention should be paid to familial aggregation. Accordingly, we suggest that primary open-angle glaucoma (POAG) be classified into inherited, familial and sporadic categories. The three classes of POAG differ not only in inheritance pattern and familial aggregation but also in methodology and outcome of gene mapping. Inherited POAG follows Mendelian inheritance and has been linked to seven chromosomal loci to date by linkage analysis. Familial POAG does not show a clear pattern of Mendelian inheritance and is typically studied by sib-pair analysis and family-based association analysis, although the results often require replication in multiple samples. Interestingly, many sporadic POAG cases carry known POAG-causing mutations, suggesting genetic predisposition as well. Based on published data, we estimated that inherited and familial POAG cases may account for approximately 72% of all POAG cases. We further formulated a mathematic model to estimate disease prevalence and mutation frequency taking both ethnic background and familial aggregation into consideration. CONCLUSION: POAG appears to be mainly caused by genetic predisposition in interaction with other risk factors such as age. The suggested classification of POAG may serve as a useful guide in clinical practice and genetic studies where ethnic background and familial aggregation must be taken into consideration.

Bone mineral density-affecting genes in Africans.

BACKGROUND: We have recently reported the role of environmental exposure in the ethnic diversity of bone mineral density (BMD). Potential genetic difference has not been adequately assessed. PURPOSE: To determine allele frequencies of BMD-affecting genes and their association with BMD in Africans. METHODS: Allele frequencies at 18 polymorphic sites in 13 genes that affect BMD in Asians and/or Caucasians were determined in 143 recent immigrants (55 men and 88 women, 18-51 years of age) from sub-Saharan Sudan to the United States. Genetic association studies were performed. RESULTS: Among the 14 single-nucleotide polymorphisms (SNPs), 10 were significantly different in allele frequency between Sudanese and Asians, and 10 between Sudanese and Caucasians. Only the osteocalcin gene was not significantly different in allele frequency among Sudanese, Asians and Caucasians. Allele frequencies in the TGFB, COL1A1 and CSR genes were extremely low (<0.04) in the Sudanese. Frequencies of microsatellite alleles in four genes were significantly different among Sudanese, Asians and Caucasians. SNPs in the VDR and ERalpha genes were associated with BMD and/or BMC (bone mineral content) at several bone sites. CONCLUSIONS: Genetic difference may play a role in the ethnic diversity in BMD and/or BMC.

Bone mineral density of recent African immigrants in the United States.

BACKGROUND: Racial/ethnic difference in bone mineral density (BMD) exists. The underlying mechanism is unclear and needs investigation. PURPOSE: To determine BMD and its relation to environmental exposure in recent African immigrants. METHODS: BMD in recent sub-Saharan Sudanese immigrants (55 men and 88 premenopausal women) in the United States was measured. Analysis of covariance (ANCOVA) model was performed, with total body, spine and hip BMD as dependent variables; and sex, age, body weight, the length of stay in the United States, and milk intake as independent variables. RESULTS: BMD Z score in the spine but not total body or hip in the Sudanese immigrants was significantly lower compared with the normative values of African Americans and Caucasians. Total body and hip BMD was positively correlated (p < 0.015) with their length of stay in the United States. Hip BMD was significantly correlated with milk intake (p < 0.02) and marginally (p = 0.052) with their length of stay in the United States, independent of body weight. CONCLUSIONS: Spinal BMD was significantly lower in recent Sudanese immigrants than in African Americans or Caucasians. Their hip and total body BMD was associated with their length of stay in the United States, suggesting a potential environmental factors in the ethnic diversity of BMD.

Dimensions of clinical medicine: an interclerkship program.

BACKGROUND: During the 3rd year of medical school, clerkships provide essential clinical experiences. However, other aspects of patient care may be overlooked during this critical phase of medical education. Faced with the challenge of integrating "orphan" topics central to effective and compassionate medical practice, medical schools have begun to develop interclerkships or intersessions. DESCRIPTION: The Dimensions of Clinical Medicine (DCM) interclerkship series at Creighton University included evidence-based medicine, sexuality in clinical medicine, palliative care, professionalism, cultural sensitivity/awareness, complementary and alternative medicine, bioterrorism, and clinical ethics. Each interclerkship comprises 2 half-day sessions conducted at the end of each clerkship rotation. EVALUATION: Students approved of the interclerkship format and valued the active learning strategies employed in the course. Many students felt the time allotted for each program was excessive. We describe educational issues and practical concerns that are central to an effective intersession program. CONCLUSION: The interclerkship format is a viable approach for incorporating orphan topics into the clinical curriculum.