Role of HLA Class II Loci Polymorphism in the Manifestation of Type 1 Diabetes in a Bengali Indian Patient Population.
Genet Test Mol Biomarkers. 2012 Nov 2;
Authors: Raha O, Sarkar B, Veerraju P, Sudhakar G, Raychaudhuri P, Mukhopadhyay S, Rao VR
To assess the contribution of the HLA class II region for susceptibility to type 1 diabetes mellitus (T1DM), we investigated the association of HLA class II alleles-DP, DQ, and DRB1. Here, we present an extensive molecular typing for HLA class II alleles and their haplotypes in a Bengali-speaking Indian population of T1DM patients (n=151) and controls (n=151) from West Bengal. HLA typing was done by DNA sequencing using a 3730 DNA Analyzer. The individual analysis of each gene gave the following alleles to be higher in cases than in controls, thus making them susceptible alleles-DPA1*020103, DPB1*020102, DQA1*050101, DQA1*0201, and DQB1*020101G. Similarly, the following alleles are protective alleles in our study-DPA1*010602, DPB1*040101, DQA1*010201, DQA1*0103, and DRB1*15. Our result confidently establishes that HLA-DP allelic, and its haplotypic, diversity contributes significantly to the risk for T1DM. The DQA1*0103 allele is a novel allele with a significant association with the protection from T1DM. Among the various haplotypes tested, the DQA1*0201:DQB1*020101G, DQA1*050101:DQB1*020101G, and DQA1*0201:DQB1*030101G were the most frequently found in T1DM patients. In India, very few investigations have been undertaken to study the impact of the genetic background on the risk to develop T1DM in its population, where the annual average incidence is 10.5/100,000/year. In conclusion, the present study highlights the genetic effect of HLA haplotypes that contributes to the susceptibility to T1DM.
PMID: 23121162 [PubMed - as supplied by publisher]
Anaplastic large-cell lymphoma in a child with type I diabetes and unrecognised coeliac disease.
Case Rep Pediatr. 2012;2012:269689
Authors: Sharp J, Pizer B, Kokai G, Auth MK
Screening for coeliac disease is recommended for children from certain risk groups, with implications for diagnostic procedures and dietetic management. The risk of a malignant complication in untreated coeliac disease is not considered high in children. We present the case of a girl with type I diabetes who developed weight loss, fatigue, and inguinal lymphadenopathy. Four years before, when she was asymptomatic, a screening coeliac tTG test was positive, but gluten was not eliminated from her diet. Based on clinical examination, a duodenal biopsy, and an inguinal lymph node biopsy were performed, which confirmed both coeliac disease and an anaplastic large-cell lymphoma. HLA-typing demonstrated that she was homozygous for HLA-DQ8, which is associated with higher risk for celiac disease, more severe gluten sensitivity, and diabetes susceptibility. She responded well to chemotherapy and has been in remission for over 4 years. She remains on a gluten-free diet. This is the first case reporting the association of coeliac disease, type I diabetes, and anaplastic large-cell lymphoma in childhood. The case highlights the malignancy risk in a genetically predisposed individual, and the possible role of a perpetuated immunologic response by prolonged gluten exposure.
PMID: 23082267 [PubMed - in process]
HLA-DQA1 and HLA-DQB1 in Celiac disease predisposition: practical implications of the HLA molecular typing.
J Biomed Sci. 2012 Oct 11;19(1):88
Authors: Megiorni F, Pizzuti A
ABSTRACT: Celiac disease (CD) is a multifactorial disorder with an estimated prevalence in Europe and USA of 1:100 and a female:male ratio of approximately 2:1. The disorder has a multifactorial etiology in which the triggering environmental factor, the gluten, and the main genetic factors, Human Leukocyte Antigen (HLA)-DQA1 and HLA-DQB1 loci, are well known. About 90-95% of CD patients carry DQ2.5 heterodimers, encoded by DQA1*05 and DQB1*02 alleles both in cis or in trans configuration, and DQ8 molecules, encoded by DQB1*03:02 generally in combination with DQA1*03 variant. Less frequently, CD occurs in individuals positive for the DQ2.x heterodimers (DQA1=*05 and DQB1*02) and very rarely in patients negative for these DQ predisposing markers. HLA molecular typing for Celiac disease is, therefore, a genetic test with a negative predictive value. Nevertheless, it is an important tool able to discriminate individuals genetically susceptible to CD, especially in at-risk groups such as first-degree relatives (parents, siblings and offspring) of patients and in presence of autoimmune conditions (type 1 diabetes, thyroiditis, multiple sclerosis) or specific genetic disorders (Down, Turner or Williams syndromes).
PMID: 23050549 [PubMed - as supplied by publisher]
[Susceptibility genes, HLA and diabetic retinopathy in the Algerian population.]
J Fr Ophtalmol. 2012 Sep 13;
Authors: Raache R, Hennachi R, Amroune H, Heniche A, Belanteur K, Benyahia A, Ouandjeli KS, Barar A, Houhou D, Mimouni S, Gervais T, Latinne D, Boudiba A, Attal N, Abbadi MC
BACKGROUND: Diabetic retinopathy (DR) is the most frequent microvascular complication of type I diabetes (T1D). Some well-controlled type I diabetics may develop DR, while other poorly-controlled diabetics do not develop DR. This might be explained by certain susceptibility genes or protective genes. The purpose of our study is to search for any association between the HLA class I and II markers and DR in the Algerian population. PATIENTS AND METHODS: This study was carried out in 52 T1D subjects with and without DR compared to 140 healthy controls. HLA typing was performed using the "microlymphocytotoxicity" technique. RESULTS: The frequency of HLA-A29 and HLA-DR9 antigens is higher in T1D with DR compared to T1D without DR and to controls with frequencies of HLA-A29 (59.26% vs. 0%, OR=∞, pc=4.6×10(-7)), (59.26% vs. 5.66%, OR=24.24, pc=7.6×10-10) and HLA-DR9 (29.63% vs. 0%, OR=∞, pc=1.310(-3)), (29.63% vs. 4.29%, OR=9.40, pc=7.010(-5)) respectively. However, the frequency of HLA-B49 antigen is significantly lower in T1D with DR than in T1D without DR (3.7% vs. 28%, OR=0.10, pc=8.8×10(-3)) and compared to controls (3.7% vs. 22.64%, OR=0.13, pc=0.011). CONCLUSION: HLA-A29 and HLA-DR9 antigens are probably markers of susceptibility for DR while HLA-B49 antigen is probably associated with a protective effect in the Algerian population.
PMID: 22981956 [PubMed - as supplied by publisher]