Association of HLA class II markers with autoantibody-negative ketosis-prone atypical diabetes compared to type 2 diabetes in a population of sub-Saharan African patients

Aim We investigated the association of HLA DRB1 and DQB1 alleles, haplotypes and genotypes with unprovoked antibody-negative ketosis-prone atypical diabetes (A − KPD) in comparison to type 2 diabetes (T2D). Methods A − KPD and T2D sub-Saharan African patients aged 19–63 years were consecutively recruited. Patients positive for cytoplasmic islet cell, insulin, glutamic acid decarboxylase or islet antigen-2 autoantibodies were excluded. Odds ratios were obtained via logistic regression after considering alleles with a minimum frequency of 5% in the study population. Bonferroni correction was used in the case of multiple comparisons. Results Among the 130 participants, 35 (27%) were women and 57 (44%) were A − KPD. DRB1 and DQB1 allele frequencies were similar for both A − KPD and T2D patients; they did not confer any substantial risk even after considering type 1 diabetes susceptibility and resistance alleles. We found no association between A − KPD and the derived DRB1*07-DQB1*02:02 (OR: 0.55 [95%CI: 0.17–1.85], P = 0.336); DRB1*11-DQB1*03:01 (OR: 2.42 [95%CI: 0.79–7.42], P = 0.123); DRB1*15-DQB1*06:02 (OR: 0.87 [95%CI: 0.39–1.95], P = 0.731) and DRB1*03:01-DQB1*02:01 (OR: 1.48 [95%CI: 0.55–3.96], P = 0.437) haplotypes. Overall, we did not find any evidence of susceptibility to ketosis associated with DRB1 and DQB1 genotypes (all P > 0.05) in A − KPD compared to T2D. Similar results were obtained after adjusting the analysis for age and sex. Conclusion Factors other than DRB1 and DQB1 genotype could explain the propensity to ketosis in A − KPD. These results need to be confirmed in a larger population with the perspective of improving the classification and understanding of the pathophysiology of A − KPD.