Frequency of HLA-DQB1*0201/02 and DQB1*0302 alleles and tissue transglutaminase antibody seropositivity in children with type 1 diabetes mellitus
ASIAN PACIFIC JOURNAL OF ALLERGY AND IMMUNOLOGY
Authors: Hammarakcharoen, Thanita; Hirankarn, Nattiya; Sahakitrungruang, Taninee, I; Thongmee, Thanunrat, I; Kuptawintu, Pavinee; Kanoonthong, Sriprapai; Chongsrisawat, Voranush
Abstract
Background: Patients with type 1 diabetes mellitus (T1DM) have an increased risk of celiac disease (CD). Both diseases have a common genetic susceptibility locus in the human leukocyte antigen (HLA) class II alleles. Testing for tissue transglutaminase antibodies (anti-tTG) is highly accurate for a CD diagnosis. Objective: To determine the frequency of HLA-DQBI*0201/02 and DQBI*0302 alleles and anti-tTG seropositivity in children with T1DM. Method: Forty-six children with T1DM (male: female=24:22; mean age 12 +/- 3.7 years) without significant digestive symptoms were enrolled. The mean duration of diabetes was 5 +/- 3.5 years. Serum anti-tTG IgA and IgG as well as HLA-DQ2 (DQBI*0201/02) and -DQ8 (DQBI*0302) alleles were analyzed. The allele frequencies were compared with those in controls, which included 124 normal Thai individuals, as reported in our previous study. Results: All subjects were negative for anti-tTG IgG. Only one patient (2.2%) was positive for anti-tTG IgA (38.5 U/mL; cut-off 15 U/mL). Although this patient was also heterozygous for HLA-DQ2 and was asymptomatic for CD, he declined endoscopic confirmation. Twenty-nine of 46 patients carried HLA-DQ2 and/or -DQ8 heterodimers. HLA-DQB1*0201/02 and HLA-DQB1*0302 allele frequencies were significantly higher (27% and 14%) in T1DM patients compared with normal controls (13.3% and 7.3%; P<0.001 and P=0.002, respectively). Conclusions: A significantly greater frequency of DQBI*0201/02 and DQBI*0302 alleles were present in children with T1DM compared with the control group. This indicates a potentially important role of these alleles in the development of T1DM. The prevalence of CD screening by serologic testing is negligible in Thai children with T1DM.
REPLICATION OF TWO INDEPENDENT LOCI IN HLA-DQB1 AND HLA-B CONTRIBUTING TO THE RISK OF CLOZAPINE-INDUCED AGRANULOCYTOSIS
EUROPEAN NEUROPSYCHOPHARMACOLOGY
Authors: Konte, Bettina; Giegling, Ina; Legge, Sophie; Cohen, Dan; Pirmohamed, M.; Tiihonen, Jari; Hartmann, Annette; Bogers, J. P.; van der Weide, J.; van der Weide, K.; Putkonen, A.; Repo-Tiihonen, Eila; Hallikainen, T.; Silva, E.; Ingimarsson, O.; Sigurdsson, Engilbert; Kennedy, James L.; Breen, Gerome; Sullivan, Patrick; Rietschel, Marcella; Stefansson, Hreinn; Collier, D. A.; O'Donovan, Michael; Rujescu, Dan
Abstract