Disease relevance of HLA-DQB1

• Genetic susceptibility to multiple sclerosis is associated with genes of the major histocompatibility complex (MHC), particularly HLA-DRB1 and HLA-DQB1 (ref. 1). Both locus and allelic heterogeneity have been reported in this genomic region [1].
• HLA-DQB1-defined genetic susceptibility, beta cell autoimmunity, and metabolic characteristics in familial and nonfamilial insulin-dependent diabetes mellitus. Childhood Diabetes in Finland (DiMe) Study Group [2].
• Association of polar amino acids at position 26 of the HLA-DQB1 first domain with the anticentromere autoantibody response in systemic sclerosis (scleroderma) [3].
• Association of amino acid sequences in the HLA-DQB1 first domain with antitopoisomerase I autoantibody response in scleroderma (progressive systemic sclerosis) [4].
• A common major histocompatibility complex class II allele HLA-DQB1* 0301 is present in clinical variants of pemphigoid [5].

Psychiatry related information on HLA-DQB1

• HLA-DQB1 typing was performed in 60 Caucasian subjects with sleepwalking (SW) disorder and their families and 60 ethnically matched subjects without any diagnosed sleep disorder [6].
• We studied infant feeding patterns and childhood diet by structured questionnaire (n = 725) and HLA-DQB1 genotype by a polymerase chain reaction-based method (n = 556) in siblings of affected children and followed them for clinical type 1 diabetes [7].
• Moreover, the monitoring of patients with concomitant celiac and autoimmune thyroid diseases, after a gluten-free diet or a gluten-containing diet, can give important insights into the effect of dietary habits in thyroid autoantibodies modulation [8].
• CASE REPORT: We treated a 22-year-old white female who carried the concomitant diagnoses of Schizophrenia, IDDM, and Hypothyroidism with quetiapine and risperidone on an acute basis at our inpatient facility, and observed an apparent resolution of her brittle diabetes with the successful treatment of her psychotic disorder [9].
• Rheumatoid arthritis in a patient with Asperger's syndrome and IDDM [10].

High impact information on HLA-DQB1

• The autoimmune disease type 1 diabetes mellitus (insulin-dependent diabetes mellitus, IDDM) has a multifactorial etiology [11].
• There are two main IDDM1 susceptibility haplotypes, HLA-DR3 and -DR4, which are present in 95% of Caucasian cases [12].
• We have now analysed the M:F ratio according to genotype at the major locus, the major histocompatibility complex (MHC; IDDM1) [12].
• Only four regions of the genome outside IDDM1/MHC, which was still the only major locus detected, were not excluded at lambda(s)=3 and lod=-2, of which two showed evidence of linkage: chromosome 10p13-p11 (maximum lod score (MLS)=4.7, P=3x10(-6), lambda(s)=1.56) and chromosome 16q22-16q24 (MLS=3.4, P=6.5x10(-5), lambda(s)=1.6) [13].
• Iron deficiency complicating celiac sprue is usually attributed to the malabsorption of dietary iron or the loss of iron from the intestinal mucosa [14].

Chemical compound and disease context of HLA-DQB1

• Although HLA-DQB1 alleles encoding aspartic acid at position 57 (Asp-57) are protective against Type 1 (insulin-dependent) diabetes mellitus in Caucasians, most Japanese Type 1 diabetic patients carry at least one Asp-57 DQB1 allele [15].
• METHODS: The distribution of HLA-DQB1 and DRB1, DRB3, DRB4, and DRB5 in 269 HCWs with latex allergy, 56 latex-sensitized patients with spina bifida (SB), and 90 nonatopic control subjects under special consideration for hevein-specific IgE was examined [16].
• HLA-DQB1 and DRB1 alleles in Egyptian children with steroid-sensitive nephrotic syndrome [17].
• Tumor necrosis factor, tumor necrosis factor receptors type 1 and 2, lymphotoxin-alpha, and HLA-DRB1 gene polymorphisms in human T-cell lymphotropic virus type I associated myelopathy [18].
• In conclusion, an alanine at codon 17 of CTLA4 is associated with genetic susceptibility to Graves' disease as well as to IDDM [19].

Biological context of HLA-DQB1

• Thus, HLA-DQB1 GL alleles, or other genes on haplotypes (e.g., DR3) that carry these DQA1 alleles, may confer recessive low responsiveness to insulin [20].
• These data suggest that genetic predisposition to the antitopo I response in PSS is associated most closely with the HLA-DQB1 locus [4].
• Primary etiological components of IDDM1, the HLA-DQB1 and -DRB1 class II immune response genes, and of IDDM2, the minisatellite repeat sequence in the 5' regulatory region of the insulin gene on chromosome 11p15, have been identified [21].
• We have scanned 12 Mb of the MHC and flanking chromosome regions with microsatellite polymorphisms and analyzed the transmission of these marker alleles to diabetic probands from parents who were homozygous for the alleles of the HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes [22].
• We investigated, in the founder population of Sardinia, whether non-DQ/DR polymorphic markers within a 9.452 Mb region encompassing the whole HLA complex further influence the disease risk, after taking into account linkage disequilibrium with the disease loci HLA-DQB1, -DQA1 and -DRB1 [23].

Anatomical context of HLA-DQB1

• HLA-C and HLA-DQB1 compatibility in unrelated cord blood transplants [24].
• We studied the association of human leukocyte antigen (HLA)-DRB1 and HLA-DQB1 alleles and HLA haplotypes with juvenile rheumatoid arthritis (JRA) in 65 patients and 65 controls from Colombia [25].
• HLA-DQB1* and DRB1* alleles recognized by ascites and supernatants from SCID-derived cultures were analyzed by microlymphocytotoxicity assay on a small panel of B-lymphoblastoid cell lines [26].
• HLA-DQA1 and HLA-DQB1 haplotypes in aborted fetuses and couples with recurrent spontaneous abortion [27].
• Identification of HLA-DRB1 and HLA-DQB1 identical individuals by a cytokine-based mixed lymphocyte culture [28].

Associations of HLA-DQB1 with chemical compounds

• A shared amino acid sequence in HLA-DQB1 (at position 26 of leucine and position 30 of tyrosine) was strongly associated with anti-P positivity (70%) versus anti-P negativity (42%) across ethnic lines [29].
• HLA-DQB1 alleles and absence of Asp 57 as susceptibility factors of IDDM in Finland [30].
• It has been suggested that protection from disease may be conferred by HLA-DQB1 genes which encode molecules with aspartate at position 57 [31].
• CONCLUSIONS: Latex-fruit allergy is associated with HLA-DQB1 *0201, DRB1 *0301, and *0901, as well as with HLA-DR functional group E, whereas latex-not-fruit allergy is associated with DQB1 *0202, and with both DRB1 *0701 and *1101 alleles [32].
• The presence of at least one HLA-DQB1 allele not coding for leucine at position 26 of the first domain appeared necessary, although not sufficient for the generation of ACA [33].

Regulatory relationships of HLA-DQB1

• All DR1-positive patients and controls carried the DQA1*0101 and DQB1*0501 alleles [34].
• METHODS: Sixty-nine IDDM patients and 47 healthy controls in a Southern Chinese population were HLA-DQB1 genotyped by one-step sequence specific polymerase chain reaction (ssPCR) [35].
• These data suggest that in addition to alleles at the DRB1 and DQB1 loci, polymorphism at the DPB1 locus may also influence IDDM risk [36].
• We typed 285 IDDM patients and 337 HLA-DRB1-DQA1-DQB1 genotypically matched control subjects from an ethnically homogeneous population for both the G/T polymorphism in intron 6 of the LMP7 gene and the Arg-His polymorphism in the LMP2 gene [37].
• Thirty-one Ethiopian insulin-dependent (or type I) diabetes mellitus (IDDM) patients and thirty-three healthy controls from the same ethnic background were typed for HLA-A, B, C, DR and DQ specificities [38].

Other interactions of HLA-DQB1

• MHC haplotypes were defined by analyzing polymorphic markers for 11 genes or their products between the HLA-DQB1 and the HLA-A genes [39].
• These data provide new limits for IDDM susceptibility to the 190-kb interval between TAP1 and HLA-DQB1 [40].
• RESULTS: DQ3 (DQBI*03 and *04 combined with DQA1*03) and DQ5 (DQB1*0501/DQA1*0101) alleles predisposed individuals to RA independently of SE-positive DRB1 alleles [41].
• Analysis of TAP gene polymorphisms will provide better understanding of susceptibility loci in HLA class II-associated disease because TAP genes are located between HLA-DQB1 and HLA-DPB1 loci [42].
• CONCLUSION: The data show genetic evidence suggesting that, in Colombians, a region immersed or in the vicinity in the HLA class II system is strongly associated with a predisposition to acquire pSS, which is probably located between the TAP2 and HLA-DQB1 locus [43].

Analytical, diagnostic and therapeutic context of HLA-DQB1

• HLA-DQB1 polymorphism determines incidence, onset, and severity of collagen-induced arthritis in transgenic mice. Implications in human rheumatoid arthritis [44].
• HLA-DRB1, HLA-DQB1, and TCRBV gene polymorphisms were studied in Thai individuals with SAE (n = 18), with vaccination without neurological complications (n = 43), and without vaccination (n = 140) [45].
• DNA was extracted from blood samples and studied by Southern blot hybridisation techniques and the following probe enzyme combinations: HLA-DQB1; Taq 1, HLA-DQA1; Taq 1, HLA-DRA; Bgl II, insulin gene hypervariable region; Pvu II and the switch region of the immunoglobulin IgM heavy chain gene (S mu); Sac I [46].
• RESULTS: HLA-DQB1 *0201 allele was found to be the primary genetic determinant of susceptibility to type 2 AIH by conferring the highest odd-ratio (OR=6.4) [47].
• To define the limit of c-ALL susceptibility within the HLA region, we have compared HLA-DQB1 allele frequencies in a cohort of 62 children with c-ALL with 76 newborn controls, using group-specific polymerase chain reaction (PCR) amplification, and single-strand conformation polymorphism (SSCP) analysis [48].

References