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Researchers at the National Institute of Health released the largest genomic study of type 2 diabetes (T2D) in sub-Saharan Africans, with data from more than 5,000 people from Nigeria, Ghana, and Kenya. The researchers confirmed the existence of known genomic variants and identified a new gene, ZRANB3, that could affect susceptibility to the disease in sub-Saharan African populations. The gene could also influence the development of T2DM in other populations and inform future research.
In a study published in the journal Nature The communications, researchers badyzed available genomic data on participants in the Africa America Diabetes Mellitus study, the largest genomic diabetes badociation study conducted on the continent. Using available information from 5,231 individuals, they discovered that many genomic variants were significantly badociated with T2DM.
The results reproduce the results of many variants already implicated in T2DM in populations of predominantly European ancestry. The work was funded by the National Institute for Human Genome Research (NHGRI), the National Institute of Diabetes and Digestive and Kidney Diseases and the Office of the Director of the National Institutes of Health.
<img alt = "Type 2 diabetes mellitus" data-align = "center" data-caption = "Representative image of the pancreas Beta cells of the pancreas produce insulin, the absence of which can cause diabetes type 2. Credit: Ernesto del Aguila III, NHGRI. & nbsp; High resolution download on Flickr. "data-entity-type =" file "data-entity-uuid =" 0b861c13-d898-4d56-a8d7-8563ba6e80e5 "src =" http://www.genome.gov/sites/default/files/inline-images/ type2diabetes.jpg "/>
"Africa is the original cradle of all humanity, to which all humans can trace their genetic origin," said Francis S. Collins, MD, Ph.D., co-author of the paper and lead investigator of NHGRI Medical Genomics and Metabolic. Direction of genetics. "Thus, studying the genomes of Africans offers important opportunities to understand genetic variation across all human populations."
To better understand how ZRANB3 was involved in T2D, the researchers studied its effects on the zebrafish pancreas. The pancreas is one of the key organs involved in T2D because its β cells release insulin in response to increased glucose in the blood.
"At the beginning of large-scale genomic studies, we did not know the effect of the genes that we found through our statistical tests," said Dr. Adebowale Adeyemo, a researcher at NHGRI and the author's first author. article. "But with the availability of new genomic tools, our next step was to ask: what is ZRANB3 doing? How does it confer a risk of T2D and by what mechanisms does it work? This is the knowledge that will help the results to become actionable for the patients. "
In collaboration with Dr. Norann Zaghloul of the University of Maryland, the researchers used a CRISPR-Cas9 DNA modification system to make the ZRANB3 gene ineffective in zebrafish (called "knockout"). They also used biological tools to reduce ZRANB3 gene expression in different zebrafish. In both cases, the researchers observed a reduction in the number of β cells in the developing zebrafish embryo. They understood that it was because the β cells were being destroyed when the ZRANB3 gene was inactive.
To track these results and identify the consequences of such β-cell death, the researchers took β-cell cells from mice and performed similar ZRANB3 gene deletion as in the zebrafish model. They found that cells with ZRANB3 knockdown released much less insulin in the presence of higher glucose than normal mouse β cells.
Although the role of ZRANB3 in T2DM has been discovered in African populations (which have been largely underrepresented in genomic research), it is possible that the same gene also influences the development of T2D in others. populations, while scientists are studying further the biology of this gene, according to the researchers.
In fact, the function of genes is, in most cases, universally identical. However, differences in sequence variations in a gene, as well as in how they interact with lifestyle, behavior, and other factors, may influence the impact of a gene. gene on the disease in a given population.
"The results of this study further demonstrate why it is important to study all human populations. In doing so, we have the opportunity to make new discoveries that will help not only a specific population but also people from around the world, "said Dr. Charles Rotimi, lead author of the paper. "Biology then becomes generalizable, and that much more impact."
The next steps for the researchers will be to return to the human participants with T2DM as well as the variant of ZRANB3. The question is: does the presence of the ZRANB3 variant in patients with T2D can help predict whether these people will need insulin at the beginning of their diabetes treatment? Providing insulin early to these people may be advantageous as it may help delay the depletion of their β cells over time. This could one day be a simple, but extremely effective, way to treat T2D in a personalized way.
National Institute for Human Genome Research (NHGRI) is one of the 27 institutes and centers of the NIH, an agency of the Ministry of Health and Social Services. The NHGRI Intramural Research Division develops and implements technology to understand, diagnose and treat genomic and genetic diseases. Additional information on NHGRI is available at www.genome.gov.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Part of NIH, conducts and supports basic and clinical research and research training on some of the most common, serious and disabling conditions affecting Americans. The research areas of the Institute include diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition and obesity; and renal, urological and hematological diseases. For more information, visit www.niddk.nih.gov.
National Institutes of Health (NIH) is the country's medical research agency, comprises 27 institutes and centers and is part of the US Department of Health and Human Services. NIH is the lead federal agency responsible for leading and supporting basic, clinical and translational medical research. They study the causes, treatments and remedies for common and rare diseases. For more information on NIH and its programs, visit www.nih.gov.
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