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

Shitaye A Balcha, Abayneh G Demisse, Rajashree Mishra, Tanwi Vartak, Diana L Cousminer, Kenyaita M Hodge, Benjamin F Voight, Kim Lorenz, Stanley Schwartz, Samuel T Jerram, Arla Gamper, Alice Holmes, Hannah F Wilson, Alistair J K Williams, Struan F A Grant, R. David Leslie, David I. W Phillips, Elisabeth R Trimble*

*Corresponding author for this work

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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 < 0.0001). The mean type 1 diabetes genetic risk score (derived from European data) was higher in patients than control participants (p = 1.60 × 10−7 ). Interestingly, despite the modest sample size, autoantibody-positive patients revealed evidence of association with SNPs in the well-characterised MHC region, already known to explain half of type 1 diabetes heritability in Europeans. Conclusions/interpretation The majority of patients with insulin-dependent diabetes in rural North-West Ethiopia have the immunogenetic characteristics of autoimmune type 1 diabetes. Phenotypic differences between type 1 diabetes in rural NorthWest Ethiopia and the industrialised world remain unexplained.
Original languageEnglish
Number of pages11
JournalDiabetologia
DOIs
Publication statusPublished - 23 Jul 2020

Keywords

  • Africa
  • autoantibodies
  • Ethiopia
  • genomes
  • HLA
  • rural
  • type 1 diabetes

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    Balcha, S. A., Demisse, A. G., Mishra, R., Vartak, T., Cousminer, D. L., Hodge, K. M., Voight, B. F., Lorenz, K., Schwartz, S., Jerram, S. T., Gamper, A., Holmes, A., Wilson, H. F., Williams, A. J. K., Grant, S. F. A., Leslie, R. D., Phillips, D. I. W., & Trimble, E. R. (2020). Type 1 diabetes in Africa: an immunogenetic study in the Amhara of North-West Ethiopia. Diabetologia. https://doi.org/10.1007/s00125-020-05229-x