HLA-DR3 and HLA-DR4 Positivity in Young-Onset Diabetes in Bangladesh: A Pilot Case–Control Study

A bstract Background: Human leukocyte antigen (HLA) class II markers HLA-DR3 and HLA-DR4 are well-established genetic markers associated with autoimmune diabetes. However, data from Bangladesh are limited, especially in clinically heterogeneous young-onset diabetes. Objective: To describe the frequencies of HLA-DR3 and HLA-DR4 positivity in Bangladeshi individuals with clinically heterogeneous young-onset diabetes and compare them with those of age- and sex-matched normoglycemic controls. Methodology: The current pilot case–control study recruited 35 young individuals with diabetes and 35 individuals (age- and sex-matched) with normal glucose tolerance (NGT). Clinical and anthropometric data were recorded. HLA-DR3 and HLA-DR4 positivity was detected by extraction of genomic DNA from peripheral blood, polymerase chain reaction, and gel electrophoresis. Results: HLA-DR3 positivity was observed in 8.6% (3/35) of participants with diabetes and in none of the controls ( P = 0.239). HLA-DR4 positivity was detected in 22.9% (8/35) of the diabetes group and 28.6% (10/35) of controls ( P = 0.785). Within the diabetes group, no significant demographic, clinical, or biochemical differences were observed between participants who were positive for HLA-DR3/HLA-DR4 and those who were negative for both markers. Family history of diabetes ( P < 0.001) and acanthosis nigricans ( P = 0.031) were more common, and waist-to-hip ratio ( P = 0.007) and diastolic blood pressure ( P = 0.001) were higher in the diabetes group than in the NGT group. Conclusions: In clinically heterogeneous young-onset diabetes in Bangladesh, broad HLA-DR3 and HLA-DR4 positivity did not differ significantly from those of normoglycemic controls. Further studies with refined phenotyping and higher-resolution immunogenetic assessment are required.