期刊
DIABETOLOGIA
卷 63, 期 10, 页码 2158-2168出版社
SPRINGER
DOI: 10.1007/s00125-020-05229-x
关键词
Africa; Autoantibodies; Ethiopia; Genomes; HLA; Rural; Type 1 diabetes
资金
- Association of Physicians of Great Britain and Ireland
- NIH [RO1 DK085212, NIH1K99HD099330-01]
- Daniel B. Burke Endowed Chair for Diabetes Research
- Type 1 Diabetes UK [DUK 19/0005951]
- EFSD [MMBP1C3R]
- EU [EU-FP7:282510]
- St Bartholomew's Hospital, London, Charity [OGA011582]
- British Diabetic Twin Trust
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 andHLA-DRB1alleles. 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) andHLA-DRB1*04(p = 0.0001) were positively associated with this form of diabetes, whileHLA-DRB1*15was 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 x 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 North-West Ethiopia and the industrialised world remain unexplained.
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