Type 1 diabetes in Africa: an immunogenetic study in the Amhara of North-West Ethiopia.

ABSTRACT: AIMS/HYPOTHESIS:We aimed to characterise the immunogenic background of insulin-dependent diabetes in a resource-poor rural African community. The study was initiated because reports of low autoantibody prevalence and phenotypic differences from European-origin cases with type 1 diabetes have raised doubts as to the role of autoimmunity in this and similar populations. METHODS:A study of consecutive, unselected cases of recently diagnosed, insulin-dependent diabetes (n?=?236, ?35 years) and control participants (n?=?200) was carried out in the ethnic Amhara of rural North-West Ethiopia. We assessed their demographic and socioeconomic characteristics, and measured non-fasting C-peptide, diabetes-associated autoantibodies and HLA-DRB1 alleles. Leveraging genome-wide genotyping, we performed both a principal component analysis and, given the relatively modest sample size, a provisional genome-wide association study. Type 1 diabetes genetic risk scores were calculated to compare their genetic background with known European type 1 diabetes determinants. RESULTS:Patients presented with stunted growth and low BMI, and were insulin sensitive; only 15.3% had diabetes onset at ?15 years. C-peptide levels were low but not absent. With clinical diabetes onset at ?15, 16-25 and 26-35 years, 86.1%, 59.7% and 50.0% were autoantibody positive, respectively. Most had autoantibodies to GAD (GADA) as a single antibody; the prevalence of positivity for autoantibodies to IA-2 (IA-2A) and ZnT8 (ZnT8A) was low in all age groups. Principal component analysis showed that the Amhara genomes were distinct from modern European and other African genomes. HLA-DRB1*03:01 (p?=?0.0014) and HLA-DRB1*04 (p?=?0.0001) were positively associated with this form of diabetes, while HLA-DRB1*15 was protective (p?

SUBMITTER: Balcha SA 

PROVIDER: S-EPMC7476916 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature