GAD65 antibody prevalence and association with c-peptide, HLA class II alleles in Beninese patients with type 1 diabetes

Background: Antibodies to glutamic acid decarboxylase and particularly their isoforms in 65 kDa are one of markers for the diagnosis of the type 1 diabetes (T1D). The aim of this study is to assess the prevalence of GAD65 antibodies (GAD65Ab) and investigate the association of GAD65Ab with C-peptide values, HLA Class II alleles genotyping. The diagnosis of T1D was set up according to American Diabetes Association criteria.Methods: Radioimmunoassay was used to determine the GAD65Ab and C-peptide values. Class II HLA genotyping was performed in 51 patients with T1D and 51 healthy unrelated as control by using the PCR-SSP method. The sensitivity and specificity of the tests were calculated by standard formula.Results: Result revealed that GAD65Ab were present in 74.5% (38/51) of the patients with T1D. There was no significant difference between the positivity or the negativity of GAD65Ab and gender, onset and duration of diabetes, frequencies of HLA-DR4, HLA-DR3-DR4, HLA-DQB1*0201. However, GAD65Ab values are linked to C-peptide concentration (χ2 =15.73, P=0.0001), the presence of HLA-DR3 (χ2 =9.75, P= 0.002), HLA-DQA1*0501 (χ2 =4.09, P= 0.043) alleles. The GAD65Ab test sensitivity and specificity were 74.5% and 94.1%, respectively. The C-peptide test showed a sensitivity around 82.4 % and 86.3 % for the specificity.Conclusions: GAD65Ab showed to be a valuable early predictive marker and is associated with the risk to develop of T1D.

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HLA class II alleles and autoantibodies in Mexican-American families with type 1 diabetes

Diabetes Research and Clinical Practice ◽

10.1016/s0168-8227(00)81760-x ◽

2000 ◽

Vol 50 ◽

pp. 89

Author(s):

Adina Zeidler ◽

LeslieJ. Raffel ◽

SylviaJ. Shaw ◽

Janelle Noble ◽

JeromeI. Rotter ◽

...

Keyword(s):

Type 1 Diabetes ◽

Mexican American ◽

Class Ii ◽

Hla Class Ii ◽

Mexican American Families ◽

Hla Class Ii Alleles ◽

American Families

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HLA class II alleles in Norwegian patients with coexisting type 1 diabetes and celiac disease

HLA ◽

10.1111/tan.12986 ◽

2017 ◽

Vol 89 (5) ◽

pp. 278-284 ◽

Cited By ~ 13

Author(s):

M. K. Viken ◽

S. T. Flåm ◽

T. Skrivarhaug ◽

S. S. Amundsen ◽

L. M. Sollid ◽

...

Keyword(s):

Type 1 Diabetes ◽

Celiac Disease ◽

Class Ii ◽

Hla Class Ii ◽

Hla Class Ii Alleles

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HLA Class II Allele, Haplotype, and Genotype Associations with Type 1 Diabetes in Benin: A Pilot Study

Journal of Diabetes Research ◽

10.1155/2017/6053764 ◽

2017 ◽

Vol 2017 ◽

pp. 1-4 ◽

Cited By ~ 3

Author(s):

Kaossarath A. Fagbemi ◽

Thierry C. Marc Medehouenou ◽

Simon Azonbakin ◽

Marius Adjagba ◽

Razack Osseni ◽

...

Keyword(s):

Type 1 Diabetes ◽

Odds Ratio ◽

American Diabetes Association ◽

Class Ii ◽

Hla Class Ii ◽

Hla Dr ◽

Hla Genotyping ◽

Set Up ◽

Hla Class Ii Alleles

Background. Several studies have reported the implication of HLA-DR/DQ loci in the susceptibility to type 1 diabetes (T1D). Since no such study has yet been performed in Benin, this pilot one aimed at assessing HLA class II allele, haplotype, and genotype associations with T1D. Material and Methods. Class II HLA genotyping was performed in 51 patients with T1D and 51 healthy unrelated controls by means of the PCR-SSP method. The diagnosis of T1D was set up according to American Diabetes Association criteria. Odds ratio (OR) and its 95% confidence interval (95% CI) were calculated to assess the associations between T1D and HLA alleles, haplotypes, and genotypes. Results. Participants were aged 1–24 years. T1D was significantly associated with DR3, DQA1∗05:01, DQB1∗02:01, and DR3-DR4. No significant associations were observed with DR4, DQB1∗03:02, and DQB1∗06:02. Conclusion. Certain HLA class II alleles, haplotypes, and genotypes were related to T1D and may be used as genetic susceptibility markers to T1D in Benin.

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HLA Class II Haplotypes Differentiate Between the Adult Autoimmune Polyglandular Syndrome Types II and III

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-2852 ◽

2014 ◽

Vol 99 (1) ◽

pp. E177-E182 ◽

Cited By ~ 24

Author(s):

B. K. Flesch ◽

N. Matheis ◽

T. Alt ◽

C. Weinstock ◽

J. Bux ◽

...

Keyword(s):

Type 1 Diabetes ◽

Addison’S Disease ◽

Class Ii ◽

Hla Class Ii ◽

Addison's Disease ◽

Type Ii ◽

Autoimmune Thyroid ◽

Autoimmune Polyglandular Syndrome ◽

Hla Class Ii Alleles

Background: Genetics of the adult autoimmune polyglandular syndrome (APS) is poorly understood. Aim: The aim of this study was to gain further insight into the genetics of the adult APS types. Site: The study was conducted at a university referral center. Methods: The human leukocyte antigen (HLA) class II alleles, haplotypes, and genotypes were determined in a large cohort of patients with APS, autoimmune thyroid disease (AITD), and type 1 diabetes and in healthy controls by the consistent application of high-resolution typing at a four-digit level. Results: Comparison of the allele and haplotype frequencies significantly discriminated patients with APS vs AITD and controls. The HLA class II alleles DRB1*03:01 *04:01, DQA1*03:01, *05:01, DQB1*02:01, and *03:02 were observed more frequently (P < .001) in APS than in AITD and controls, whereas the alleles DRB1*15:01, DQB1*03:01, and *06:02 were underrepresented in APS vs AITD (Pc < .001) and controls (Pc < .01), respectively. The DRB1*03:01-DQA1*05:01-DQB1*02:01 (DR3-DQ2) and DRB1*04:01-DQA1*03:01:DQB1*03:02 (DRB1*04:01-DQ8) haplotypes were overrepresented in APS (Pc < .001). Combination of both haplotypes to a genotype was highly prevalent in APS vs AITD and controls (Pc < .001). Dividing the APS collective into those with Addison's disease (APS type II) and those without Addison's disease but including type 1 diabetes and AITD (APS type III) demonstrated DR3-DQ2/DRB1*04:01-DQ8 as a susceptibility genotype in APS III (Pc < .001), whereas the DR3-DQ2/DRB1*04:04-DQ8 genotype correlated with APS II (Pc < .001). The haplotypes DRB1*11:01-DQA1*05:05-DQB1*03:01 and DRB1*15:01-DQA1*01:02-DQB1*06:02 are protective in APS III but not in type II (Pc < .01). Conclusions: HLA class II haplotypes differentiate between the adult APS types II and III. Susceptible haplotypes favor the development of polyglandular autoimmunity in patients with AITD.

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Role of HLA Class II Loci Polymorphism in the Manifestation of Type 1 Diabetes in a Bengali Indian Patient Population

Genetic Testing and Molecular Biomarkers ◽

10.1089/gtmb.2012.0221 ◽

2013 ◽

Vol 17 (1) ◽

pp. 52-61 ◽

Cited By ~ 1

Author(s):

Oindrila Raha ◽

Biswanath Sarkar ◽

Pasumarthy Veerraju ◽

Godi Sudhakar ◽

Pradip Raychaudhuri ◽

...

Keyword(s):

Type 1 Diabetes ◽

Patient Population ◽

Class Ii ◽

Hla Class Ii ◽

Indian Patient

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Association of HLA Class II Alleles and Haplotypes with Type 1 Diabetes in Tunisian Arabs

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/a-0754-5586 ◽

2018 ◽

Vol 127 (10) ◽

pp. 653-662

Author(s):

Abdelhafidh Hajjej ◽

Wassim Y. Almawi ◽

Mouna Stayoussef ◽

Lasmar Hattab ◽

Slama Hmida

Keyword(s):

Type 1 Diabetes ◽

Association Studies ◽

Class Ii ◽

Correlation Study ◽

Case Control ◽

Linkage Study ◽

Hla Class Ii ◽

Racial Background ◽

Family Based

AbstractThe molecular association of HLA class II with type 1 diabetes (T1DM) was investigated in Tunisian Arabs using 3 kinds of analyses. The first was a case-control association study, using Relative Predispositional Effects method, involved 137 T1DM cases and 258 control subjects. The second was family-based association-linkage study, using Transmission Disequilibrium Test, and covering 50 Tunisian families comprising 73 T1DM patients and 100 parents. The third was a wide correlation study between 4 DRB1 alleles (DRB1*03, *04, *11, *15) and T1DM in 52 countries, using Spearman’s Rho. Results from Case-control and family-based association studies showed that DRB1*03 and DRB1*04 alleles predispose to T1DM in Tunisian Arabs. Conversely, only DRB1*11 was protective for T1DM. DRB1*04-DQB1*03 haplotype was consistently associated positively with T1DM; DRB1*03/DRB1*04 genotype had the highest risk of T1DM development. Compared to DRB1*03, HLA-DRB1*04 was associated with higher T1DM incidence. Thus, the contribution of HLA class II to T1DM genetic susceptibility must be evaluated with regards to specific HLA alleles, genotypes, and haplotypes, and also ethnic and racial background.

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Major Histocompatibility Complex Class II (HLA-DRB and -DQB) Allele Frequencies in Botswana: Association with Human Immunodeficiency Virus Type 1 Infection

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.12.9.1020-1028.2005 ◽

2005 ◽

Vol 12 (9) ◽

pp. 1020-1028 ◽

Cited By ~ 17

Author(s):

Thumbi Ndung'u ◽

Simani Gaseitsiwe ◽

Enoch Sepako ◽

Florence Doualla-Bell ◽

Trevor Peter ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Class Ii ◽

Hla Class Ii ◽

Common Allele ◽

Immunodeficiency Virus ◽

Hiv 1 ◽

Hla Class Ii Alleles

ABSTRACT Southern Africa is facing an unprecedented public health crisis due to the high prevalence of human immunodeficiency virus type 1 (HIV-1). Vaccine development and testing efforts, mainly based on elicitation of HIV-specific T cells, are under way. To understand the role of human leukocyte antigen (HLA) class II alleles in HIV pathogenesis and to facilitate HLA-based HIV-1 vaccine design, we analyzed the frequencies of HLA class II alleles within the southern African country of Botswana. Common HLA class II alleles were identified within the Batswana population through the molecular genotyping of DRB and DQB1 loci. The DRB1 allele groups DRB1*01, DRB1*02/15, DRB1*03, DRB1*11, and DRB1*13 were encountered at frequencies above 20%. Within the DQB1 locus, DQB1*06 (47.7%) was the most common allele group, followed by DQB1*03 (39.2%) and DQB1*04 (25.8%). We found that DRB1*01 was more common in HIV-negative than in HIV-positive individuals and that those who expressed DRB1*08 had lower median viral loads. We demonstrate that the frequencies of certain HLA class II alleles in this Batswana population differ substantially from those in North American populations, including African-Americans. Common allele groups within Botswana cover large percentages of other African populations and could be targeted in regional vaccine designs.

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Susceptible and Protective Human Leukocyte Antigen Class II Alleles and Haplotypes in Bahraini Type 2 (Non-Insulin-Dependent) Diabetes Mellitus Patients

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.12.1.213-217.2005 ◽

2005 ◽

Vol 12 (1) ◽

pp. 213-217 ◽

Cited By ~ 8

Author(s):

Ayesha A. Motala ◽

Marc Busson ◽

Einas M. Al-Harbi ◽

Manal A. A. Khuzam ◽

Emtiaz M. D. Al-Omari ◽

...

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Human Leukocyte Antigen ◽

Human Leukocyte ◽

Class Ii ◽

Hla Class Ii ◽

Leukocyte Antigen ◽

Insulin Dependent

ABSTRACT Whereas the genetic risk for type 1 diabetes is linked to human leukocyte antigen (HLA) class II genes, the HLA association in type 2 (non-insulin-dependent) diabetes is less clear. The association between HLA class II genotypes and type 2 diabetes was examined in adult Bahrainis, an Arab population with a high prevalence of type 2 diabetes. HLA-DRB1* and -DQB1* genotyping of 86 unrelated type 2 diabetes patients (age, 51.6 ± 8.2 years; mean duration of diabetes, 7.7 ± 7.1 years) who had a strong family history of diabetes (52 of 72 versus 0 of 89 for controls, P < 0.001) and 89 healthy subjects was done by PCR-sequence-specific priming. DRB1*040101 (0.1221 versus 0.0562, P = 0.019) and DRB1*070101 (0.2151 versus 0.0843, P < 0.001) were positively associated, while DRB1*110101 (0.0698 versus 0.1461, P = 0.014) and DRB1*160101 (0.0640 versus 0.1236, P = 0.038) were negatively associated with type 2 diabetes. DRB1*040101-DQB1*0302 (0.069 versus 0.0007; P = 0.004), DRB1*070101-DQB1*0201 (0.178 versus 0.0761, P = 0.007), DRB1*070101-DQB1*050101 (0.125 versus 0.0310, P = 0.002), and DRB1*150101-DQB1*060101 (0.0756 versus 0.0281, P = 0.008) were more prevalent among patients, while DRB1*160101-DQB1*050101 (0.0702 versus 0.0349, P = 0.05) was more prevalent among controls, conferring disease susceptibility or protection, respectively. In Bahrainis with type 2 diabetes, there is a significant association with select HLA class II genotypes, which were distinct from those in type 1 diabetes.

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HLA Class II Allele Analyses Implicate Common Genetic Components in Type 1 and Non–Insulin-Treated Type 2 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa027 ◽

2020 ◽

Vol 105 (3) ◽

pp. e245-e254 ◽

Cited By ~ 1

Author(s):

Thomas Jacobi ◽

Lucas Massier ◽

Nora Klöting ◽

Katrin Horn ◽

Alexander Schuch ◽

...

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Class Ii ◽

Hla Class Ii ◽

Risk Haplotype ◽

Genetic Components ◽

Hla Genotypes ◽

Increased Risk

Abstract Context Common genetic susceptibility may underlie the frequently observed co-occurrence of type 1 and type 2 diabetes in families. Given the role of HLA class II genes in the pathophysiology of type 1 diabetes, the aim of the present study was to test the association of high density imputed human leukocyte antigen (HLA) genotypes with type 2 diabetes. Objectives and Design Three cohorts (Ntotal = 10 413) from Leipzig, Germany were included in this study: LIFE-Adult (N = 4649), LIFE-Heart (N = 4815) and the Sorbs (N = 949) cohort. Detailed metabolic phenotyping and genome-wide single nucleotide polymorphism (SNP) data were available for all subjects. Using 1000 Genome imputation data, HLA genotypes were imputed on 4-digit level and association tests for type 2 diabetes, and related metabolic traits were conducted. Results In a meta-analysis including all 3 cohorts, the absence of HLA-DRB5 was associated with increased risk of type 2 diabetes (P = 0.001). In contrast, HLA-DQB*06:02 and HLA-DQA*01:02 had a protective effect on type 2 diabetes (P = 0.005 and 0.003, respectively). Both alleles are part of the well-established type 1 diabetes protective haplotype DRB1*15:01~DQA1*01:02~DQB1*06:02, which was also associated with reduced risk of type 2 diabetes (OR 0.84; P = 0.005). On the contrary, the DRB1*07:01~DQA1*02:01~DQB1*03:03 was identified as a risk haplotype in non–insulin-treated diabetes (OR 1.37; P = 0.002). Conclusions Genetic variation in the HLA class II locus exerts risk and protective effects on non–insulin-treated type 2 diabetes. Our data suggest that the genetic architecture of type 1 diabetes and type 2 diabetes might share common components on the HLA class II locus.

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