HLA Allele-Specific Quantitative Profiling of Type 1 Diabetic B Lymphocyte Immunopeptidome

Abstract Objectives There are several hypotheses on the effects of the rs1738074 T/C single nucleotide polymorphism in the TAGAP gene; however, there has been no study on Turkish pediatric patients. We aimed to investigate the association of celiac disease (CD) and type 1 diabetes mellitus (T1DM) comorbidity with the polymorphism in the TAGAP gene of Turkish pediatric patients. Methods Totally, 127 pediatric CD patients and 100 healthy children were included. We determined the polymorphism by the allele-specific polymerase chain reaction method. We used IBM SPSS Statistics version 25.0 and Arlequin 3.5.2 for the statistical analyses. The authors have no conflict of interest. Results It was determined that 72% (n=154) of only CD patients had C allele, whereas 28% (n=60) had T allele. Of the patients with celiac and T1DM, 42.5% (n=17) and 57.5% (n=23) had T and C alleles, respectively. Of the individuals in control group, 67% (n=134) had C allele, whereas 33% (n=66) had T allele. Conclusions There was no significant difference in the genotype and allele frequencies between the patient and control groups (p>0.05). There was no significant association between the disease risk and the polymorphism in our study group.

Download Full-text

Insulin VNTR allele-specific effect in type 1 diabetes depends on identity of untransmitted paternal allele

Nature Genetics ◽

10.1038/ng1197-350 ◽

1997 ◽

Vol 17 (3) ◽

pp. 350-352 ◽

Cited By ~ 121

Author(s):

Simon T. Bennett ◽

◽

Amanda J. Wilson ◽

Laura Esposito ◽

Nourdine Bouzekri ◽

...

Keyword(s):

Type 1 Diabetes ◽

Specific Effect ◽

Paternal Allele ◽

Allele Specific

Download Full-text

B lymphocyte alterations accompany abatacept resistance in new-onset type 1 diabetes

JCI Insight ◽

10.1172/jci.insight.126136 ◽

2019 ◽

Vol 4 (4) ◽

Cited By ~ 13

Author(s):

Peter S. Linsley ◽

Carla J. Greenbaum ◽

Cate Speake ◽

S. Alice Long ◽

Matthew J. Dufort

Keyword(s):

Type 1 Diabetes ◽

B Lymphocyte ◽

Onset Type ◽

New Onset

Download Full-text

Fine-mapping identifies causal variants for RA and T1D in DNASE1L3, SIRPG, MEG3, TNFAIP3 and CD28/CTLA4 loci

10.1101/151423 ◽

2017 ◽

Cited By ~ 5

Author(s):

Harm-Jan Westra ◽

Marta Martinez Bonet ◽

Suna Onengut ◽

Annette Lee ◽

Yang Luo ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Functional Analysis ◽

Type 1 Diabetes ◽

Specific Binding ◽

Common Variants ◽

Enhancer Activity ◽

Allele Specific ◽

Causal Variants ◽

Coding Variants

We fine-mapped 76 rheumatoid arthritis (RA) and type 1 diabetes (T1D) loci outside of the MHC. After sequencing 799 1kb regulatory (H3K4me3) regions within these loci in 568 individuals, we observed accurate imputation for 89% of common variants. We fine-mapped1,2 these loci in RA (11,475 cases, 15,870 controls)3, T1D (9,334 cases and 11,111 controls) 4 and combined datasets. We reduced the number of potential causal variants to ≤5 in 8 RA and 11 T1D loci. We identified causal missense variants in five loci (DNASE1L3, SIRPG, PTPN22, SH2B3 and TYK2) and likely causal non-coding variants in six loci (MEG3, TNFAIP3, CD28/CTLA4, ANKRD55, IL2RA, REL/PUS10). Functional analysis confirmed allele specific binding and differential enhancer activity for three variants: the CD28/CTLA4 rs117701653 SNP, the TNFAIP3 rs35926684 indel, and the MEG3 rs34552516 indel. This study demonstrates the potential for dense genotyping and imputation to pinpoint missense and non-coding causal alleles.

Download Full-text