A 14-year-old male presents with type I diabetes mellitus. His mother wants to know if the boy's brother might also have an increased risk of getting the disease. Which of the following genotypes, if present in the brother, would be associated with the greatest risk of developing diabetes?
High-Yield Explanation
A heterozygous individual with HLA-DR3 and HLA-DR4 has a 33-fold greater relative risk for developing diabetes than individuals without these two HLA antigens. Homozygous individuals with HLA-B27 are more likely to develop ankylosing spondylitis and Reiter's disease. Patients who are homozygous for HLA-DR2 have a reduced risk of diabetes mellitus. Individuals with the HLA-DR4 allele have an increased risk of diabetes. Heterozygotes for HLA-DR2 and HLA-DR4 likely have an intermediate risk. Ref: Powers A.C. (2012). Chapter 344. Diabetes Mellitus. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison's Principles of Internal Medicine, 18e.