ZRANB3 in African Populations: New Type 2 Diabetes risk locus identified
Last Updated on August 4, 2019 by Joseph Gut – thasso
August 03, 2019 – Africa is considered the original cradle of all humanity, to which all humans can trace their genetic origin. This may be very interesting in the context of diseases that are due to genetic predispositions both in todays African populations and in all the populations descendant of African origin worldwide.
The findings of this study further demonstrate why it is important to study all human populations. By doing so, novel discoveries that will not only help the specific population but also people all around the globe are going to be made. Moreover, in the early days of large-scale genomic studies, the effect of genes found through statistical tests were not known. Today, with the availability of new genomic tools, a logical step in the present case is to ask: What does ZRANB3 do? How does it confer risk for T2D, and by what mechanisms does it act? Are these mechanisms unique to individuals of African population descent only? What is (are) the resulting clinical phenotype(s)? Overall, this kind of studies only will eventually provide the knowledge that will help the results become actionable for patients in theragenomic medicine.
Thus, for those functional experiments, the team used RNA sequencing, CRISPR-Cas9-based gene knockouts, and other approaches for fiddling with the expression of ZRANB3 in a zebrafish pancreas model of T2D. Results from such experiments indicated that the number of insulin-producing beta cells in the pancreas decrease as ZRANB3 activity is dialed down, results confirmed with small interfering RNA-based gene knockdown experiments in mice. If confirmed in humans, these results may indicate the in the ZRANB3 affected African populations, regulation of insulin-producing beta cells may be one of the mechanisms behind T2D, and that, consequently, this regulation could become a target for therapeutic intervention.
When they looked for T2D associations with more than 100 SNPs implicated in the condition in the past, the researchers verified 32 of these risk loci in the Nigerian, Ghanaian, or Kenyan cases, among them TCF7L2rs7903146, MCM6, DARS, DGKB, GTF3AP5-AGMO, IL23R/IL12RB2, SLC44A4. A handful more risk loci came out of the GWAS meta-analysis, which included data for almost 8,600 participants from African, African American, and other populations.