ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31324766.
- Also identified by DOI 10.1038/s41467-019-10967-7 and PMC identifier 6642147.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Genome analysis of diverse human populations has contributed to the identification of novel genomic loci for diseases of major clinical and public health impact. Here, we report a genome-wide analysis of type 2 diabetes (T2D) in sub-Saharan Africans, an understudied ancestral group. We analyze ~18 million autosomal SNPs in 5,231 individuals from Nigeria, Ghana and Kenya. We identify a previously-unreported genome-wide significant locus: ZRANB3 (Zinc Finger RANBP2-Type Containing 3, lead SNP p = 2.831 × 10<sup>-9</sup>). Knockdown or genomic knockout of the zebrafish ortholog results in reduction in pancreatic β-cell number which we demonstrate to be due to increased apoptosis in islets. siRNA transfection of murine Zranb3 in MIN6 β-cells results in impaired insulin secretion in response to high glucose, implicating Zranb3 in β-cell functional response to high glucose conditions. We also show transferability in our study of 32 established T2D loci. Our findings advance understanding of the genetics of T2D in non-European ancestry populations.
Medical subject headings
- DNA Helicases
- Diabetes Mellitus, Type 2
- Genetic Association Studies
- Genetic Predisposition to Disease
- Insulin
- Insulin-Secreting Cells