Rapid genetic screening for major human leukocyte antigen risk haplotypes in patients with type 1 diabetes from Northeastern Brazil

Brandão, Lucas; Vatta, Serena; Guimarães, Rafael Lima; Segat, Ludovica; Araújo, João M. M.; Filho, José Luiz de Lima; Arraes, Luiz Cláudio; Not, Tarcisio; Crovella, Sérgio

doi:10.1016/j.humimm.2009.12.008

Cited by 10 publications

(6 citation statements)

References 27 publications

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“…The ethnic variation in the prevalence of autoantibodies among T1DM was highlighted in many early studies [26,27]. In the current study, GAD antibody and anti-IA-2 were significantly higher in siblings compared to controls.…”

Section: Discussionsupporting

confidence: 54%

HLA-DR, HLA-DQ Haplotypes and Diabetic Autoantibodies in Nondiabetic Siblings of Type I Diabetes

Awadalla¹

2015

J Diabetes Metab

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The screening of non-diabetic siblings of Saudi type 1 diabetes mellitus (T1DM) patients (n=54) and 50 healthy controls was undertaken for glutamic acid decarboxylase (anti-GAD) and antibodies to tyrosine phosphatse (IA-2) using radioimmunoprecipitation. HLA-DRB1, DQB1 and DQA1 alleles were tested by PCR and sequence-specific oligonucleotide probes. HLA analysis showed that susceptible alleles were DRB1*03:01 (61.1%) *04:01 (22.02%), DQA1*05:01 (61.1%), DQA1*03:03 (33.3%) and DQB1*02:01 (72.2%). The DRB1*03:01-DQA1*05:01-DQB1*02:01 haplotype was significantly higher among siblings (61%). The protective alleles were DRB1*04:03 (1.8%), DRB1*13 (11.1%), DQA1*02:01 (5.6%), DQA1*05:05 (5.6%), DQB1*03:01 (5.6%) and DQB1*05:01 (11.1%). GADA (22.2%) and anti-IA-2 (11.1%) were significantly higher among siblings, both antibodies present in 27.8% of siblings. The frequency of GADA was higher in those aged 5 to 10 years (50%), while IA-2 positive children were > 5years old (100%). 36.4 % of DRB1*03:01-DQA1*05:01-DQB1*02:01 sibling were positive for GADA, 18.2% were positive for IA-2 and 9.1% were positive for both antibodies. 27.8% of siblings were HLA-identical to the proband, 61.1% were haploidentical, and 11.1% were not identical. GADA was significantly higher among the HLA-identical siblings (60%) than haploidentical (9.1%) and non-identical siblings (zero). IA-2 was higher in HLA-identical (20%) from haploidentical (9.1%) and non-identical HLA (zero) but not to significant level. Both antibodies were present in 20% of HLA-identical siblings, and in none of the haplo-or non-identical HLA. In conclusion, the immunogenetic screening of nondiabetic sibling identifies individuals at risk of developing T1DM.

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Section: Discussionsupporting

confidence: 54%

HLA-DR, HLA-DQ Haplotypes and Diabetic Autoantibodies in Nondiabetic Siblings of Type I Diabetes

Awadalla¹

2015

J Diabetes Metab

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“…34,35 In a population from Brazil, T1D risk associated with both haplotypes DQ2.5 and DQ8 was confirmed using SNPs rs2187668 and rs7454108, whose association with classic HLA alleles was validated by conventional PCR-SSP methods. 36 The three SNPs reported to predict the high risk DR3/DR4-DQ2/ DQ8 haplotype (Table 4) were individually associated in our study.…”

Section: Discussionsupporting

confidence: 48%

A non‐codingRNASEH1gene variant associates with type 1 diabetes and interacts withHLA tagSNPsin families from Colombia

et al. 2020

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Objectives: RNASEH1 gene has recently been associated with type 1 diabetes (T1D) in Colombia. The purpose of this study was to fine mapping the putative functional variant in RNASEH1 and testing its interaction with HLA tagSNPs. Methods: Two-hundred nuclear families with T1D were included in this study. Probands were tested for GAD65 and IA-2 autoantibodies. Genotyping was performed using 20 coding tagSNPs uncovered through Sanger sequencing (N = 96), in addition to 23 tagSNPs chosen from 1000genomes to cover the extent of the gene region. Also, 45 tagSNPs for classic HLA alleles associated with T1D were also genotyped. The transmission disequilibrium test (TDT) was used to test for association and a multiple testing correction was made using permutation. Interaction between RNASEH1 variants and HLA was evaluated by means of the M-TDT test. Results: We identified 20 variants (15 were novel) in the 96 patients sequenced. None of these variants were in linkage disequilibrium. In total, 43 RNASEH1 variants were genotyped in the 200 families. Association between T1D and rs7607888 was identified (P = .002). Haplotype analysis involving rs7607888 variant revealed even stronger association with T1D (most significative P = .0003). HLA tagSNPs displayed stronger associations (OR = 6.39, 95% CI = 4.33-9.44, P-value = 9.74E-28). Finally, we found several statistically significant interactions of HLA variants with rs7607888 (P-value ranged from 8.77E-04 to 5.33E-12). Conclusion: Our results verify the association of rs7607888 in RNASEH1 gene with T1D. It is also shown in the interaction between RNASEH1 and HLA for conveying risk to T1D in Northwest Colombia. Work is underway aiming to identify the actual classic HLA alleles associated with the tagSNPs tested here.

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“…HLA genotyping of the healthy controls was performed using a Tag-SNPs approach as reported by Monsuur et al ( 15 ) and Koskinen et al ( 16 ). Th e choice of the Tag-SNPs method for HLA genotyping was based on its low cost, high throughput, and our track record of using this method ( 17 ).…”

Section: Patients and Controlsmentioning

confidence: 99%

The Missense Variation Q705K in CIAS1 / NALP3 / NLRP3 Gene and an NLRP1 Haplotype Are Associated With Celiac Disease

Pontillo

Vendramin

Catamo

et al. 2011

American Journal of Gastroenterology

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Rapid genetic screening for major human leukocyte antigen risk haplotypes in patients with type 1 diabetes from Northeastern Brazil

Cited by 10 publications

References 27 publications

HLA-DR, HLA-DQ Haplotypes and Diabetic Autoantibodies in Nondiabetic Siblings of Type I Diabetes

HLA-DR, HLA-DQ Haplotypes and Diabetic Autoantibodies in Nondiabetic Siblings of Type I Diabetes

A non‐codingRNASEH1gene variant associates with type 1 diabetes and interacts withHLA tagSNPsin families from Colombia

The Missense Variation Q705K in CIAS1 / NALP3 / NLRP3 Gene and an NLRP1 Haplotype Are Associated With Celiac Disease

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