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

作者：Balti Eric V; Ngo Nemb Marinette C; Lontchi Yimagou Eric; Atogho Tiedeu Barbara; Effoe Valery S; Akwo Elvis A; Dehayem Mesmin Y; Mbanya Jean Claude; Gautier Jean Francois; Sobngwi Eugene^*

来源：Diabetes Research and Clinical Practice, 2015, 107(1): 31-36.

DOI：10.1016/j.diabres.2014.10.002

• Ketosis-prone diabetes
• Autoantibody-negative
• Type 2 diabetes
• HLA
• Genetic markers

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: 01DQB1*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.

• 出版日期2015-1