HLA-DRB, -DQA, and DQB alleles and haplotypes in Iranian patients with diabetes mellitus type I.

Specific alleles at the HLA-DRB1, -DQA1, and -DQB1 loci seem to be associated with variable risks of developing type 1 diabetes (T1D). This study assessed the distribution of HLA-DR and -DQ alleles among Iranian T1D patients and healthy controls. In this study, HLA-DRB1, -DQA1, and -DQB1 alleles were determined in 100 children with T1D and 100 unrelated healthy controls. The following alleles were found to have a strong positive association with T1D: DRB1*0301, DRB1*0401, DRB1*0402, DQA1*0301, DQA1*0501, DQB1*0201, and DQB1*0302. Meanwhile, protective associations were found for DRB1*1001, DRB1*1101, DRB1*15, DRB1*16, DQA1*0102, DQA1*0103, DQB1*0301, DQB1*0501, and DQB1*0602 alleles. The haplotypes found most frequently among patients with T1D were DRB1*0301-DQA1*0501-DQB1*0201, DRB1*0401-DQA1*0301- DQB1*0302, and DRB1*0402-DQA1*0301-DQB1*0302, whereas DRB1*1101-DQA1*0501-DQB1*0301 and DRB1*16-DQA1*0102- DQB1*0501 haplotypes were negatively associated with the disease. These results confirm the previously reported association of specific HLA-DR and HLA-DQ alleles and haplotypes with T1D in Iranian population. The notable difference was the identification of DRB1*16-DQA1*0102-DQB1*0501 as a protective haplotype and the absence of a negative association of DRB1*1301-DQA1*0103-DRB1*0603 with T1D.

Rabbani A ，Abbasi F ，Taghvaei M ，Rabbani B ，Moradi B ，Shakiba Y ，Rezaei N ，Amirzargar A ... -  《-》

Association of HLA-DRB1 and -DQ Alleles and Haplotypes with Type 1 Diabetes in Jordanians.

The Human Leukocyte Antigen (HLA) class II genes, particularly the HLADR and -DQ loci, have been shown to play a crucial role in Type 1 Diabetes (T1D) development. This study is the first to examine the contribution of the HLA-DR/DQ alleles and haplotypes to T1D susceptibility in Jordanians. Polymerase chain reaction sequence-specific primers (PCR-SSP) were used to genotype 41 Jordanian healthy controls and 50 insulin-dependent diabetes mellitus (IDDM) patients. The following alleles were found to be significant high risk alleles in T1D Jordanian patients: DRB1*04 (OR=3.95, p<0.001), DRB1*0301(OR=5.27, p<0.001), DQA1*0301 (OR=5.67, p<0.001), DQA1*0501(OR=3.18, p=0.002), DQB1*0201(OR=2.18, p=0.03), DQB1*0302 (OR=5.67, p<0.001). However, Jordanians harboring the DRB1*0701 (OR=0.37, p=0.01), DRB1*1101 (OR=0.2, p=0.01), DQA1*0505 (OR=0.31, p=0.02), DQA1*0103 (OR=0.33, p=0.04), DQA1*0201 (OR=0.45, p=0.04), DQB1*0301 (OR=0.23, p=0.001), DQB1*0501 (OR=0.18, p=0.009) alleles had a significantly lower risk of developing T1D. A strong positive association of DRB1*04-DQA1*0301-DQBl*0302 (OR=5.67, p<0.001) and DRB1*0301-DQA1*0501-DQB1*0201 (OR=6.24, p<0.001) putative haplotypes with IDDM was evident in Jordanian IDDM patients whereas DRB1*1101-DQA1*0505- DQB1*0301 (OR=0.23, p=0.03) was shown to have a protective role against T1D in Jordanians. Our findings show that specific HLA class II alleles and haplotypes are significantly associated with susceptibility to T1D in Jordanians.

Khdair SI ，Jarrar W ，Jarrar YB ，Bataineh S ，Al-Khaldi O ... -  《-》

Association between HLA alleles and haplotypes with age at diagnosis of type 1 diabetes in an admixed Brazilian population: A nationwide study.

To investigate the potential relationship between HLA alleles and haplotypes and the age at diagnosis of type 1 diabetes (T1DAgeD) in an admixed Brazilian population. This nationwide study was conducted in public clinics across 12 Brazilian cities. We collected demographic and genetic data from 1,600 patients with T1D. DNA samples were utilised to determine genomic ancestry (GA) and perform HLA typings for DRB1, DQA1 and DQB1. We explored allele and haplotype frequencies and GA in patients grouped by T1DAgeD categories (<6 years, ≥6-<11 years, ≥11-<19 years and ≥19 years) through univariate and multivariate analyses and primary component analyses. Additionally, we considered self-reported colour-race and identified a familiar history of T1D in first-degree relatives. The homozygosity index for DRB1~DQA1~DQB1 haplotypes exhibited the highest variation among T1DAgeD groups, and the percentages of Sub-Saharan African and European ancestries showed opposite trends in principal component analysis (PCA) analyses. Regarding the association of alleles and haplotypes with T1DAgeD, risk alleles such as HLA-DQB1*03:02g, -DQA1*03:01g, -02:01g, DRB1*04:05g and -04:02g were more frequently observed in heterozygosity or homozygosity in T1D patients with an early disease onset. Conversely, alleles such as DRB1*07:01g, -13:03g, DQB1*06:02g and DQA1*02:01 were more prevalent in older T1D patients. The combination DR3/DR4.5 was significantly associated with early disease onset. However, gender, GA, familiar history of T1D and self-reported colour-race identity did not exhibit significant associations with the onset of T1D. It is worth noting that the very common risk haplotype DRB1*03:01g~DQA1*05:01g~DQB1*02:01g did not differentiate between T1DAgeD groups. In the admixed Brazilian population, the high-risk haplotype DRB1*04:05~DQA1*03:01~DQB1*03:02 was more prevalent in individuals diagnosed before 6 years of age. In contrast, the protective alleles DQA1*01:02g, DQB1*06:02g, DRB1*07:01g and DRB1*13:03g and haplotypes DRB1*13:03g~DQA1*05:01g~DQB1*03:01g and DRB1*16:02g~DQA1*01:02g~DQB1*05:02g were more frequently observed in patients diagnosed in adulthood. Notably, these associations were independent of factors such as sex, economic status, GA, familiar history of T1D and region of birth in Brazil. These alleles and haplotypes contribute to our understanding of the disease onset heterogeneity and may have implications for early interventions when detected in association with well-known genomic risk or protection factors for T1D.

Gomes MB ，Dos Santos GC Jr ，de Sousa Azulay RS ，Santos DC ，Silva DA ，Carvalho PRVB ，Negrato CA ，Porto LC ... -  《-》

The influence of the HLA-DRB, HLA-DQB and polymorphic positions of the HLA-DRβ1 and HLA-DQβ1 molecules on risk of Iranian type 1 diabetes mellitus patients.

Type 1 Diabetes mellitus (T1D) is an autoimmune and multifactorial disease. HLA-DRB1 and DQB1 loci have the strongest association with T1D. This study aimed at investigating (i) susceptibility or protection of alleles, genotypes and haplotypes of HLA-DRB1 and DQB1 loci; and (ii) highly polymorphic amino acid residues of HLA-DRβ1 and DQβ1 in 105 Iranian T1D patients and 100 controls. The results indicated that DRB1*04:01, 03:01, DQB1*03:02, 02:01 alleles, DRB1*03:01/04:01, 03:01/13:03, DQB1*02:01/03:02 genotypes, DRB1*04:01-DQB1*03:02, DRB1*03:01-DQB1*02:01, DRB1*07:01-DQB1*03:03 haplotypes had positive association with T1D. In contrast, HLA-DRB1*15:01, 13:01, DQB1*03:01, 06:01 alleles, DRB1*11:01/15:01, DQB1*03:01/06:01, 03:01/05:01 genotypes and DRB1*15:01-DQB1*06:01, DRB1*11:01-DQB1*03:01 haplotypes had negative association with T1D. Analysis of amino acid sequence of HLA-DRβ1 and DQβ1 revealed that DRβ1(Lys71+) and DQβ1(Asp57-) were significantly more frequent in patients than in controls and had a positive effect in the development of T1D. Haplotype analysis demonstrated that HLA-DRB1(Lys71+) allele provided major susceptibility for T1D, and DQβ1(Asp57-) had an additive effect. We designed an allele-specific primer to develop an easy, quick and cost-benefit method to detect the DRβ1(Lys71+) . This method can identify all 114 DRB1 alleles encoding DRβ1(Lys71+) by three PCR reactions. The PcPPV and PcNPV were also calculated to determine the impact of HLA genotype testing at amino acid positions. It showed that the DRβ1(Lys71+/+) genotype carrier had 1% absolute risk of developing T1D.

Sayad A ，Akbari MT ，Pajouhi M ，Mostafavi F ，Zamani M ... -  《-》

HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families.

Erlich H ，Valdes AM ，Noble J ，Carlson JA ，Varney M ，Concannon P ，Mychaleckyj JC ，Todd JA ，Bonella P ，Fear AL ，Lavant E ，Louey A ，Moonsamy P ，Type 1 Diabetes Genetics Consortium ... -  《-》