HLA‐associated genetic resistance and susceptibility to type I diabetes in French North Africans and French natives

Abstract

The distribution of human leukocyte antigen (HLA)-DRB1-DQA1-DQB1 haplotypes was analyzed separately in two distinct French ethnic groups with type I diabetes (T1D), i.e. French North African migrants (n= 64, mean age at diagnosis = 8.25 years) and ancient French natives (n= 60, mean age at diagnosis = 7.42 years). HLA associations were determined by calculating odds ratios (ORs) between patients and two ethnic-matched control populations. Results show highly similar ORs for the conservative DRB1*0301-DQA1*0501-DQB1*0201 haplotype of susceptibility (OR: 3.22 and 3.93 in migrants and natives, respectively) and the DRB1*1501-DQA1*0102-DQB1*0602 haplotype of resistance (OR: 0.05 and 0.03, respectively). In contrast, among the more variable DRB1*04-DQB1*0302 haplotypes of susceptibility, the DRB1*0402 (OR: 3.10 and 32.84) and 0405 (OR: 5.90 and 16.25, respectively) were associated with T1D in migrants and natives, whereas an increase of DRB1*0401, a rare allele in migrants, was significant in natives only. Also, among the DRB1*11-DQA1*0505-DQB1*0301 haplotypes of resistance, the OR observed for DRB1*1104-DQA1*0505-DQB1*0301, common in migrants, was lower (OR: 0.08) than for DRB1*1101-DQA1*0505-DQB1*0301 (OR: 0.32), common in natives. How DRB1*11 subtypes might affect differently the risk conferred by DQA1*0505-DQB1*0301 will be discussed.

Human leucocyte antigens class II allele and haplotype association with Type 1 Diabetes in Madeira Island (Portugal)

“…Among our samples, DQA1*05:05 allele is in strong linkage with DQB1*03:01 (Table ), a protective allele (Table ) that codes for an Aspartic acid in the position 57 (Asp57), a feature highly associated with T1D protection (Table ). Also, variation in the protective effect of DQA1*05:05‐DQB1*03:01 has been referred to depend on DRB1 contribution, suggesting it could be a consequence of a Valine at codon 86 (Guérin et al., ). However, in the present study, a Valine in DRB1 position 86 associated to DQA1*05:05 does not reveal a significant protection effect (OR = 0.58, p = .46), even when considering the total sample (OR = 0.91, p = .61), but this lack of significance could be just a consequence of the small sample size.…”

Trends in the Frequency of HLA DR-DQ Haplotypes Among Children and Adolescents with Type 1 Diabetes Mellitus in the Southeast Region of Turkey

“…The incidence of T1DM is rapidly increasing in specific regions and shows a trend toward earlier age of onset and also it is highly variable among different ethnic groups (6,7,8,9,10,11,12,13,14,15). It is predicted that the overall incidence of T1DM is about 40% higher in recent years as compared to its incidence in 1997 (16).…”

“…T1DM is an autoimmune disorder and the risk for the disease is increased by specific HLA DR/DQ alleles [e.g., DRB1*03-DQB1*0201 (DR3) or DRB1*04-DQB1*0302 (DR4)] (2,3,4,5). Trends in the frequency of HLA DR-DQ haplotypes showed different associations in distinct ethnic groups (6,7,8,9,10,11,12,13,14,15) and also in the same region (11). With these variations in mind, T1DM patients and healthy controls from the population of the Southeast Region of Turkey were investigated for HLA DR-DQ haplotypes.…”

Genetic Determinants of Type 1 Diabetes: Immune Response Genes

“…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].…”