HLA DR/DQ alleles and risk of type I diabetes in childhood: a population–based case–control study

Abstract

The objective was to evaluate HLA DR/DQ alleles and their risk factor for type 1 diabetes in the Abruzzo region (central Italy). Sixty incident cases from the Abruzzo region were studied together with 120 unrelated control subjects living in the same administrative areas. The relative risk of diabetes associated with the alleles under study was calculated by deriving the odds ratio (OR) maximum likelihood estimates and their 95% confidence intervals (CI) by the exponentiation of the logistic regression beta-parameter. The combination DRB1*03/DQA1*0501/DQB1*0201 was found in 20.0% of patients and 7.1% of the control subjects, conferring an OR of 4.04 and a CI of 1.97-8.49. The combination DRB1*04/DQA1*0301/DQB1*0302 was found in 23.3% of diabetic patients and 6.7% of controls, giving an OR of 5.69 and a CI of 2.77-12.05. DRB1*11/DQA1*0505/DQB1*0301 and DQA1*0505/DQB1*0301 were negatively associated with type 1 diabetes (OR=0.27, CI 0.11-0.57; OR=0.07, CI 0.02-0.19). The DQA1 genotype at risk was found to be DQA1*0301/DQA1*0501: OR=23.80, CI 2.97-190.89, as it occurred with the highest frequency in the patient group. The DQB1 genotype at risk was found to be DQB1*0201/DQB1*0302, which occurred in 13.3% of patients but in only 1.1% of the control group (OR=29.75, CI 5.36-549.25). Our results shed further light on the risk of development of this disease during a specific time period in an area where the overall incidence of type 1 diabetes is known.

Genetic and diabetic auto-antibody markers in Saudi children with type 1 diabetes

“…In this study, there was a strong association of the heterozygote DQ2/DQ8 (38.8%, OR ϭ 18.4) and DR3/DR4 (32%, OR ϭ 13.7) with T1DM; this agrees with findings in other Arab populations, such as Kuwaitis [29] and Egyptians [30], as well as in non-Arabs, such as in Spanish [31], Greeks [32], British [33], and Italians [34].…”

Genetic Determinants of Type 1 Diabetes: Immune Response Genes

“…On the contrary, this pocket in DQ2, DQ8 and DQ8.2 molecules has been reported to be similar, suggesting no importance in determining susceptibility to diabetes [88,89]. Several studies have reported an increased occurrence of DQ8 in patients of Caucasian origin [78,82,90].…”

“…In addition, DQ2 (DQB1*0201-DQA1*0501) and DQ8 (DQB1*0302-DQA1*0301), which occur in strong linkage disequilibrium with DR3 and DR4, respectively, are strongly associated with the disease in several Caucasian populations, especially when present in the DR3/DR4 heterozygous condition [78][79][80][81][82][83]. It has been suggested that DR3/DR4 heterozygosity exerts a synergistic effect and provides a much greater risk to T1D than DR3 homozygosity in most populations.…”

“…Worldwide, T1D has been reported to be strongly associated with HLA-DR3 or -DR4, or both alleles, whereas HLA-DR15 has been found to be protective in north Indians and several other populations [73][74][75][76][77][78][79][80][81][82]. In addition, DQ2 (DQB1*0201-DQA1*0501) and DQ8 (DQB1*0302-DQA1*0301), which occur in strong linkage disequilibrium with DR3 and DR4, respectively, are strongly associated with the disease in several Caucasian populations, especially when present in the DR3/DR4 heterozygous condition [78][79][80][81][82][83].…”

HLA-DQB1* alleles and genetic susceptibility to type 1 diabetes mellitus

“…To the best of our knowledge, the present study is the first to identify a positive association between HLA-DQB1*0202 and T1D (Table 2). DQB1*0201 and DQB1*0302 were positively associated with T1D in various ethnic populations including Asians [34,35] , European [36][37][38][39][40][41][42][43] , and Americans [44][45][46] . Similar results were reported for Arab patients from Saudi Arabia [47,48] , Kuwait [49] , Tunisia [50] , Lebanon [51] , and Israeli [52] .…”