Specific HLA-DRB and -DQB Alleles and Haplotypes Confer Disease Susceptibility or Resistance in Bahraini Type 1 Diabetes Patients

Abstract

ABSTRACT Insofar as genetic susceptibility to type 1 diabetes is associated with HLA class II genes, with certain allelic combinations conferring disease susceptibility or resistance, this study assessed the distributions of HLA-DR and -DQ among 107 unrelated patients with type 1 diabetes and 88 healthy controls from Bahrain, all of Arab origin. The HLA - DRB and -DQB genotypes were determined by PCR-sequence-specific priming. The following alleles showed the strongest association with type 1 diabetes among patients versus controls according to their frequencies: DRB1 * 030101 (0.430 versus 0.097; P < 0.001), DRB1 * 040101 (0.243 versus 0.034; P < 0.001), DQB1 * 0201 (0.467 versus 0.193; P < 0.001), and DQB1 * 0302 (0.229 versus 0.091; P < 0.001). When the frequencies of alleles in controls were compared to those in patients, negative associations were seen for DRB1 * 100101 (0.085 versus 0.014; P < 0.001), DRB1 * 110101 (0.210 versus 0.060; P < 0.001), DQB1 * 030101 (0.170 versus 0.075; P = 0.006), and DQB1 * 050101 (0.335 versus 0.121; P < 0.001). In addition, the DRB1 * 030101 - DQB1 * 0201 (70.1 versus 22.7%; P < 0.001) and DRB1 * 030101 - DQB1 * 0302 (21.5 versus 0.0%; P < 0.001) genotypes were more prevalent among patients, thereby conferring disease susceptibility, whereas the DRB1 * 100101 - DQB1 * 050101 (20.5 versus 2.8%; P < 0.001), DRB1 * 110101 - DQB1 * 030101 (28.4 versus 8.4%; P < 0.001), and DRB1 * 110101 - DQB1 * 050101 (30.7 versus 0.9%; P < 0.001) genotypes were more prevalent among controls, thus assigning a protective role. These results confirm the association of specific HLA-DR and -DQ alleles and haplotypes with type 1 diabetes and may underline several characteristics that distinguish Bahraini patients from other Caucasians patients.