HLA-DQB1* alleles and genetic susceptibility to type 1 diabetes mellitus

Abstract

AIM:To determine human leukocyte antigen (HLA)-DQB1 allele association with susceptibility to type 1 diabetes (T1D) and to clinical and laboratory findings. METHODS:This study was conducted on 85 unrelated Egyptian children with T1D recruited consecutively from the Pediatric Diabetes Endocrinology outpatients Clinic; Mansoura University Children's Hospital, Egypt. Patient mean follow up period was 2.5 years. Patients were subdivided according to level of HbA1c (optimal/suboptimal control < 8.5% and poor control ≥ 8.5%). The control group consisted of 113 unrelated age-and sexmatched healthy subjects without T1D or other autoimmune diseases. Genomic DNA extraction was done for all subjects using a DNA isolation kit. HLA-Class Ⅱ-DQB1 allele typing was carried out with a polymerase chain reaction-sequence-specific oligonucleotide probe using a INNO-LiPA HLA-DQB1 update kit.RESULTS: Significant differences were detected between Egyptian patients with T1D and control groups in the frequencies of DQB1*02 [44.4% vs 18.6%, corrected P value (Pc ) < 0.001] and DQB1*03 (41.2% vs 24.4%, Pc < 0.001). Significant differences were also observed between control groups and T1D patients in the frequencies of DQB1*05 (14.6% vs 7.2%, P = 0.029) and DQB1*06 (34.1% vs 7.2%, P < 0.001).However, after correction for multiple comparisons, the significance was retained for HLA-DQB1*06 (Pc < 0.001) but lost for HLA-DQB1*05. HLA-DQB1*0201, *0202, *030201 were positively associated with T1D (Pc = 0.014, Pc < 0.001, and Pc < 0.001 respectively), while HLA-DQB1*060101 was negatively associated (Pc < 0.001) with the condition. Although the HLA-DQB1 alleles 030101 and 050101 were significantly higher in controls (P = 0.016, P = 0.025 respectively), both of them lost statistical significance after correction of P value. The frequency of the HLA-DQB1 genotypes 02/02, 02/03, and 03/03 was higher in T1D patients, and the frequency of the genotypes 03/06, 05/06, and 06/06 was higher in controls, these differences being statistically significant before correction. After correction, the genotypes 02/02, 02/03 in T1D, and the genotypes 03/06, 06/06 in controls were still significant (Pc = 0.01, Pc < 0.001, Pc < 0.001, and Pc = 0.04, respectively). Non-significant associations were found between the frequency HLA-DQB1 alleles and genotypes in T1D in relation to the grade of diabetic control, Microalbuminuria, age, gender, age of presentation, weight, height, frequency of diabetic ketoacidosis (P = ORIGINAL ARTICLE 149August 15, 2012|Volume 3|Issue 8|

Type 1 diabetes alters lipid handling and metabolism in human fibroblasts and peripheral blood mononuclear cells

“…Despite the strong evidence for a genetic predisposition towards T1D, epidemiological data indicating the involvement of additional environmental factor(s) in disease etiology remain compelling. The human leukocyte antigen (HLA) genotype, the dominant genetic marker for T1D, is found in only 20–30% of T1D patients, and in only 50% of patients diagnosed in early childhood [ 1 , 2 ]. In addition, less than half of HLA-susceptible monozygotic twins both develop T1D [ 3 , 4 ].…”

Identification of novel risk genes associated with type 1 diabetes mellitus using a genome‐wide gene‐based association analysis

“…Extensive evidence has shown that genetic factors play important roles in the development of type 1 diabetes mellitus. However, identification of specific responsible genes and their variants has had limited success.…”

Clinical Role of Human Leukocyte Antigen in Health and Disease

“…The association of specific HLA-DQB1 alleles and genotypes with T1D susceptibility/protection depends on the ethnicity and racial background of each population. For example, in Caucasians, T1D is positively associated with DQB1*0201 and DQB1*0302 while in Japanese, it is associated with DQB1*0401 and DQB1*0303 [156].…”