To assess the frequency of HLA class II (DPA1, DPB1, DQA1, DQB1 and DRB1) associated to susceptibility or protection toT1DM in a Bengali population of India with diabetes.
The A*2402, DRB1*0301, DRB1*0405 and DRB1*0901 alleles, and A*1101-DRB1*0901, A*2402-DRB1*0405 and A*2402-DRB1*0901 haplotypes were associated with T1D (all p<0.05).
To assess the frequency of HLA class II (DQA1, DQB1 and DRB1) associated to susceptibility or protection toT1DM in a Brazilian racially admixtured with diabetes.
HLA-DRB1*03-DQB1*0201/DRB1*04-DQB1*0302 (DR3/4-DQ8) siblings who share both major histocompatibility complex (MHC) haplotypes identical-by-descent with their proband siblings have a higher risk for type 1A diabetes than DR3/4-DQ8 siblings who do not share both MHC haplotypes identical-by-descent.
In addition, we identified markers that define DRB1*1501 DQB1*0602 haplotypes conferring reduced protection from diabetes in a Swedish 13th IHW data set.
Highest risk was conferred by the genotype DRB1*03-DQA1*0501-DQB1*0201/DRB1*0401-DQA1*0301-DQB1*0302 (5% absolute risk of diabetes by age 15 yr), although sensitivity was only 22.6%.
Three haplotypes were markedly associated with diabetes in Jewish Ethiopian patients: DRB1*0301 DQA1*05 DQB1*02 (OR 4.4, p < 0.001); DRB1*0404 DQA1 03 DQB1*0302 (OR 19.2, p = 0.006), and DRB1*0405 DQA1*03 DQB1*0302 (OR 87.8, p < 0.001).
In Japanese type 1 susceptible HLA haplotypes, DRB1*0901-DQB1*0303 was more frequent in type 1A diabetes than fulminant diabetes (7/18 vs. 0/18, P=0.004), whereas the frequency of DRB1*0405-DQB1*0401 was similar (type 1A 4/18 vs. fulminant 6/18).
A significant decreased frequency of DRB1*0403 (p = 0.01; odds ratio [OR] = 0.20) was demonstrated in type 2 diabetic patients, and DRB1*0701 (p = 0.02; OR = 0.17) in nondiabetics with family history of diabetes.
Similarly, the DRB1*0401-DQB1*0302/(DR13)-DQB1*0603 genotype was disease predisposing, implying that DQB*0603-mediated protection from diabetes is not always dominant.
A total of 13% of the GADab(+) patients with diabetes had genotypes comprising the DRB1*1501-DQB1*0602 or *1502-*0601 and were characterized by old age at onset of diabetes, high BMI, resistance to the insulin-deficient state, low titer of GADab, and low frequency of other organ-specific autoantibodies.
The presence of diabetes-resistant or neutral alleles, such as HLA DQ6 (DQB1*0602) and DR2 (DRB1*1502) prevented the generation of any self-reactive responses to rat GAD.
Our analyses indicate that the counterbalancing between susceptible DRB1 and protective DQB1, and vice versa, is a factor that may contribute to the low incidence of diabetes in Asians.
Among HLA class II haplotypes, both HLA-DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) and DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8) ("at-risk class II haplotypes") were positively associated with diabetes (OR = 6.7 and 6.0, respectively) (p(c) < 0.003).
Among patients with diabetes with DQ8, Addison's disease was strongly associated with the specific DRB1 subtype, DRB1*0404 (8 of 9 patients from 8 families, in contrast to only 109 of 408 DQ8 DM patients with diabetes without Addison's disease having DRB1*0404; P < 0.001).
The antibodies to islet cells and those to glutamic acid decarboxylase were measured in 1712 white Caucasian diabetic subjects at diagnosis of diabetes and they were genotyped for HLA DRB1*03 and DRB1*04 and the high-risk DRB1*04-DQB1* 0302 haplotype.
The genotypes DRB1* 04DQB1 *0302/DRB1*04DQB1*0302 and DRB1 *03DQB1*02/DRB1*04DQB1* 0302 were associated with an early onset of diabetes, while homozygosity for DRB1*03DQB1*02 was characterized by later onset.
Our analyses indicate that the counterbalancing act between susceptible DRB1 and protective DQB1, and vice versa, that has already been observed in Chinese and Japanese, is the major factor responsible for the low incidence of diabetes in Koreans.
DRB1*0403 protects against IDDM in Caucasians with the high-risk heterozygous DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 genotype. Belgian Diabetes Registry.