scholarly journals Estimation of Diabetes Risk in Brazilian Population by Typing for Polymorphisms in HLA-DR-DQ, INS and CTLA-4 Genes

2005 ◽  
Vol 21 (3) ◽  
pp. 139-145 ◽  
Author(s):  
Omar M. Hauache ◽  
André F. Reis ◽  
Carolina S.V. Oliveira ◽  
José Gilberto H. Vieira ◽  
Minna Sjüroos ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 1 Diabetes ◽  
Gene Polymorphisms ◽  
Diabetes Risk ◽  
Brazilian Population ◽  
Healthy Controls ◽  
Typing Method ◽  
Hla Dr ◽  
Screening Sensitivity

The study aimed to further characterise HLA encoded risk factors of type 1 diabetes (T1D) in Brazilian population and test the capability of a low resolution full-house DR-DQ typing method to find subjects at diabetes risk. Insulin and CTLA-4 gene polymorphisms were also analysed. The method is based on an initial DQB1 typing supplemented by DQA1 and DR4 subtyping when informative. Increased frequencies of both (DR3)-DQA1*05-DQB1*02 and DRB1*04-DQA1*03-DQB1*0302 haplotypes were detected among patients. DRB1*0401, *0402, *0404 and *0405 alleles were all common in DQB1*0302 haplotypes and associated with T1D. (DRB1*11/12/1303)-DQA1*05-DQB1*0301, (DRB1*01/10)-DQB1*0501, (DRB1*15)-DQB1*0602 and (DRB1*1301)-*0603 haplotypes were significantly decreased among patients. Genotypes with two risk haplotypes or a combination of a susceptibility associated and a neutral haplotype were found in 78 of 126 (61.9%) T1D patients compared to 8 of 75 (10.7%) control subjects (P< 0.0001). Insulin gene −2221 C/T polymorphism was also associated with diabetes risk: CC genotype was found among 83.1% of patients compared to 69.3% of healthy controls (P= 0.0369, OR 1.98) but CTLA-4 gene +49 A/G polymorphism did not significantly differ between patients and controls. Despite the diversity of the Brazilian population the screening sensitivity and specificity of the used method for T1D risk was similar to that obtained in Europe.

scholarly journals Additive and interaction effects at three amino acid positions in HLA-DQ and HLA-DR molecules drive type 1 diabetes risk

2015 ◽  
Vol 47 (8) ◽  
pp. 898-905 ◽  
Author(s):  
Xinli Hu ◽  
Aaron J Deutsch ◽  
Tobias L Lenz ◽  
Suna Onengut-Gumuscu ◽  
Buhm Han ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Amino Acid ◽  
Interaction Effects ◽  
Diabetes Risk ◽  
Hla Dr ◽  
Hla Dq

scholarly journals Annexin V+ Microvesicles in Children and Adolescents with Type 1 Diabetes: A Prospective Cohort Study

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Vibeke Bratseth ◽  
Hanna D. Margeirsdottir ◽  
Gemma Chiva-Blanch ◽  
Martin Heier ◽  
Svein Solheim ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 1 Diabetes ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Vascular Dysfunction ◽  
Annexin V ◽  
Healthy Controls ◽  
Diabetes Group

Background. Type 1 diabetes is a chronic disease including hyperglycemia and accelerated atherosclerosis, with high risk of micro- and macrovascular complications. Circulating microvesicles (cMVs) are procoagulant cell fragments shed during activation/apoptosis and discussed to be markers of vascular dysfunction and hypercoagulability. Limited knowledge exists on hypercoagulability in young diabetics. We aimed to investigate cMVs over a five-year period in children/adolescents with type 1 diabetes compared with controls and any associations with glycemic control and cardiovascular risk factors. We hypothesized increased shedding of cMVs in type 1 diabetes in response to vascular activation. Methods. The cohort included type 1 diabetics (n=40) and healthy controls (n=40), mean age 14 years (range 11) at inclusion, randomly selected from the Norwegian Atherosclerosis and Childhood Diabetes (ACD) study. Citrated plasma was prepared and stored at -80°C until cMV analysis by flow cytometry. Results. Comparable levels of Annexin V (AV+) cMVs were observed at inclusion. At five-year follow-up, total AV+ cMVs were significantly lower in subjects with type 1 diabetes compared with controls; however, no significant differences were observed after adjusting for covariates. In the type 1 diabetes group, the total AV+, tissue factor-expressing AV+/CD142+, neutrophil-derived AV+/CD15+ and AV+/CD45+/CD15+, and endothelial-derived AV+/CD309+ and CD309+/CD34+ cMVs were inversely correlated with HbA1c (r=‐0.437, r=‐0.515, r=‐0.575, r=‐0.529, r=‐0.416, and r=‐0.445, respectively; all p≤0.01), however, only at inclusion. No significant correlations with cardiovascular risk factors were observed. Conclusions. Children/adolescents with type 1 diabetes show similar levels of AV+ cMVs as healthy controls and limited associations with glucose control. This indicates that our young diabetics on intensive insulin treatment have preserved vascular homeostasis and absence of procoagulant cMVs.

scholarly journals rs11203203 is associated with type 1 diabetes risk in population pre-screened for high-risk HLA-DR,DQ genotypes

2012 ◽  
Vol 13 (8) ◽  
pp. 611-615 ◽  
Author(s):  
Kelly Johnson ◽  
Randall Wong ◽  
Katherine J Barriga ◽  
Georgeanna Klingensmith ◽  
Anette-G Ziegler ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
High Risk ◽  
Diabetes Risk ◽  
Hla Dr

scholarly journals Cesarean Section and Interferon-Induced Helicase Gene Polymorphisms Combine to Increase Childhood Type 1 Diabetes Risk

Diabetes ◽  
2011 ◽  
Vol 60 (12) ◽  
pp. 3300-3306 ◽  
Author(s):  
E. Bonifacio ◽  
K. Warncke ◽  
C. Winkler ◽  
M. Wallner ◽  
A.-G. Ziegler
Keyword(s):  
Type 1 Diabetes ◽  
Cesarean Section ◽  
Gene Polymorphisms ◽  
Diabetes Risk ◽  
Helicase Gene ◽  
Childhood Type 1 Diabetes ◽  
Childhood Type

scholarly journals Islet Autoimmunity and HLA Markers of Presymptomatic and Clinical Type 1 Diabetes: Joint Analyses of Prospective Cohort Studies in Finland, Germany, Sweden, and the U.S.

2021 ◽  
Author(s):  
Vibha Anand ◽  
Ying Li ◽  
Bin Liu ◽  
Mohamed Ghalwash ◽  
Eileen Koski ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cohort Studies ◽  
Prospective Cohort ◽  
Diabetes Risk ◽  
Islet Autoantibodies ◽  
Islet Autoimmunity ◽  
Diabetes Incidence ◽  
Prospective Cohort Studies ◽  
Hla Dr

OBJECTIVE: To combine prospective cohort studies, by including HLA harmonization, and to estimate risk of islet autoimmunity and progression to clinical diabetes. <p>RESEARCH DESIGN AND METHODS: Prospective cohorts in Finland, Germany, Sweden and the US have followed 24,662 children at increased genetic risk for development of islet autoantibodies and type 1 diabetes. Following harmonization, the outcomes were analyzed in 16,709 infants-toddlers enrolled by age 2.5 years.</p> <p>RESULTS: In the infant-toddler cohort, 1413 (8.5%) developed at least one autoantibody confirmed at two or more consecutive visits (seroconversion), 865 (5%) developed multiple autoantibodies, and 655 (4%) progressed to diabetes. The 15-year cumulative incidence of diabetes varied in children with one, two or three autoantibodies at seroconversion: 45% (95% CI 40-52%), 85% (78-90%), and 92% (85-97%), respectively. Among those with single autoantibody, their status two years after seroconversion predicted diabetes risk: 12% (10-25%) if reverting to autoantibody negative, 30% (20-40%) if retaining single autoantibody, and 82% (80-95%) if developing multiple autoantibodies. HLA-DR-DQ affected the risk of confirmed seroconversion and progression to diabetes in children with stable single autoantibody. Their 15-year diabetes incidence for higher vs. lower risk genotypes was 40% (28-50%) vs. 12% (5-38%). The rate of progression to diabetes was inversely related to age at development of multiple autoantibodies ranging from 20%/year to 6%/year in children developing multi-positivity ≤2 years or >7.4 years, respectively. </p> <p>CONCLUSIONS: The number of islet autoantibodies at seroconversion reliably predicts 15-year type 1 diabetes risk. In children retaining single autoantibody, HLA-DR-DQ genotypes can further refine risk of progression.</p>

scholarly journals Specific HLA-DRB and -DQB Alleles and Haplotypes Confer Disease Susceptibility or Resistance in Bahraini Type 1 Diabetes Patients

2004 ◽  
Vol 11 (2) ◽  
pp. 292-296 ◽  
Author(s):  
Einas M. Al-Harbi ◽  
Abdul-Jabbar Abbassi ◽  
Hala Tamim ◽  
Fayza al-Jenaidi ◽  
Mariam Kooheji ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Genetic Susceptibility ◽  
Disease Susceptibility ◽  
Class Ii ◽  
Protective Role ◽  
Hla Class Ii ◽  
Healthy Controls ◽  
Hla Dr ◽  
Specific Priming

ABSTRACT Insofar as genetic susceptibility to type 1 diabetes is associated with HLA class II genes, with certain allelic combinations conferring disease susceptibility or resistance, this study assessed the distributions of HLA-DR and -DQ among 107 unrelated patients with type 1 diabetes and 88 healthy controls from Bahrain, all of Arab origin. The HLA-DRB and -DQB genotypes were determined by PCR-sequence-specific priming. The following alleles showed the strongest association with type 1 diabetes among patients versus controls according to their frequencies: DRB1*030101 (0.430 versus 0.097; P < 0.001), DRB1*040101 (0.243 versus 0.034; P < 0.001), DQB1*0201 (0.467 versus 0.193; P < 0.001), and DQB1*0302 (0.229 versus 0.091; P < 0.001). When the frequencies of alleles in controls were compared to those in patients, negative associations were seen for DRB1*100101 (0.085 versus 0.014; P < 0.001), DRB1*110101 (0.210 versus 0.060; P < 0.001), DQB1*030101 (0.170 versus 0.075; P = 0.006), and DQB1*050101 (0.335 versus 0.121; P < 0.001). In addition, the DRB1*030101-DQB1*0201 (70.1 versus 22.7%; P < 0.001) and DRB1*030101-DQB1*0302 (21.5 versus 0.0%; P < 0.001) genotypes were more prevalent among patients, thereby conferring disease susceptibility, whereas the DRB1*100101-DQB1*050101 (20.5 versus 2.8%; P < 0.001), DRB1*110101-DQB1*030101 (28.4 versus 8.4%; P < 0.001), and DRB1*110101-DQB1*050101 (30.7 versus 0.9%; P < 0.001) genotypes were more prevalent among controls, thus assigning a protective role. These results confirm the association of specific HLA-DR and -DQ alleles and haplotypes with type 1 diabetes and may underline several characteristics that distinguish Bahraini patients from other Caucasians patients.

scholarly journals Newborn HLA-DR,DQ genotype screening: age- and ethnicity-specific type 1 diabetes risk estimates

2005 ◽  
Vol 6 (3) ◽  
pp. 136-144 ◽  
Author(s):  
Lisa M Emery ◽  
Sunanda Babu ◽  
Teodorica L Bugawan ◽  
Jill M Norris ◽  
Henry A Erlich ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetes Risk ◽  
Risk Estimates ◽  
Hla Dr ◽  
Genotype Screening
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