The Genetic Profile from HLA and Non-HLA Loci Allows Identification of Atypical Type 2 Diabetes Patients

The complex diagnosis and treatment of diabetes highlight the need for markers to define how to monitor patients correctly during the course of their disease. Different studies demonstrate the existence of patients who cannot be clearly classified. We have previously shown that it is possible to differentiate “atypical diabetic patients” based on genotyping the HLA. In this work we show that the analysis of non-HLA related to type 1 diabetes in the INS-VNTR, SNP rs689, and rs3842753 improves the identification of these patients. We genotyped 913 individuals comprising controls from the general population and “classic” and “atypical” diabetic patients. We compared the distribution of these loci and analyzed linkage disequilibrium. The haplotype was in LD for all the SNPs that were evaluated. Regarding their association with the disease, the haplotype IAC was associated with type 1 (odds 2.60, 1.82–3.72, CI 95%) and “atypical diabetes” (odds 1.50, 1.01–2.23, CI 95%), whereas we did not observe an association with type 2 diabetes. Therefore, our results confirm that atypical diabetes is a different entity of the disease where the patient presents with a genetic background of T1D and a T2D phenotype, findings that are likely to be relevant for patient diagnosis and management in the clinic

The association between HLA DQ genetic polymorphism and type 1 diabetes

Susceptibility to the type 1 diabetes is genetically controlled and there is an increased risk associated with the presence of some specific alleles of the human leukocyte antigens class II loci (DQA1 and DQB1 genes). The purpose of this study is to evaluate the association between type 1 diabetes and HLA DQ alleles using case-parents trios in the admixed population of Uruguay composed by a mixture of Caucasian, Amerindian and Negroid populations. DQA1 and DQB1 genotyping was performed by polimerase chain reaction followed by oligospecific probes hybridization in 51 case-parents trios. The transmission disequilibrium test was used for detecting differential transmission in the HLA DQ loci. DQB1*0302 was the only allele for which preferential transmission is suggested (probability of transmission=67.56%; exact p-value TDT=0.047 uncorrected for multiple comparisons). DQA1*0301 allele showed a trend for preferential transmission without achieving statistical significance. This result wou

The association between HLA DQ genetic polymorphism and type 1 diabetes in a case-parent study conducted in an admixed population

Susceptibility to the type 1 diabetes is genetically controlled and there is an increased risk associated with the presence of some specific alleles of the human leukocyte antigens class II loci (DQA1 and DQB1 genes). The purpose of this study is to evaluate the association between type 1 diabetes and HLA DQ alleles using case-parents trios in the admixed population of Uruguay composed by a mixture of Caucasian, Amerindian and Negroid populations. DQA1 and DQB1 genotyping was performed by polimerase chain reaction followed by oligospecific probes hybridization in 51 case-parents trios. The transmission disequilibrium test was used for detecting differential transmission in the HLA DQ loci. DQB1*0302 was the only allele for which preferential transmission is suggested ( probability of transmission = 67.56%; exact p-value TDT = 0.047 uncorrected for multiple comparisons). DQA1*0301 allele showed a trend for preferential transmission without achieving statistical significance. This result would confirm the hypothesis previously advanced in a case-control study. Therefore, DQB1*0302 allele could be considered as the most important susceptibility allele for developing type 1 diabetes in Uruguay population