The HLA-D associations of type 1 (insulin-dependent) diabetes in Punjabi Asians in the United Kingdom.

Type 1 (insulin-dependent) diabetes is less common in Asian Indians than in white Caucasoids. Forty-five Punjabi Asians with Type 1 diabetes and 96 racially matched control subjects were HLA-DR typed. DR3 was increased in diabetic patients vs control subjects (82% vs 38%, p less than 10(-5)) with relative risk 7.7 and etiological fraction 0.72. DR4 was increased in diabetic patients vs control subjects (31% vs 7%, p less than 0.003) with relative risk 5.7 and etiological fraction 0.26. DR2 showed a negative association (relative risk 0.19, etiological fraction -0.28), as did DR7 (relative risk 0.21, etiological fraction -0.33). HLA-DQ beta-chain gene probing using restriction enzyme BamHI in 43 diabetic patients and 90 control subjects showed that the DR1-associated 6.2 and 3.2 kb fragments were less common in diabetic patients than in the control subjects (12% vs 36%, p less than 0.02). A 12 kb fragment was associated with DR4 in both diabetic patients and control subjects. DR3 is the major susceptibility factor for Type 1 diabetes in Punjabi Asians and DR4 is a second marker. Gene probing indicates that the same DR4 subset is associated with the condition as in white Caucasoids. DR1 and its associated DQ beta restriction fragments are reduced in Asian Type 1 diabetic patients making it unlikely that DR1 haplotypes carry a predisposing factor in this racial group. We conclude that the genetic component of Type 1 diabetes in Punjabis shows differences from that of the white Caucasoid population and that the lower frequency of DR4 in this population may contribute to the lower prevalence of Type 1 diabetes.