Higher prevalence of autoantibodies to insulin and GAD65 in Swedish compared to Lithuanian children with type 1 diabetes

被引:17
作者
Holmberg, Hanna [1 ]
Vaarala, Outi
Sadauskaite-Kuehne, Vaiva
Ilonen, Jorma
Padaiga, Zilvinas
Ludvigsson, Johnny
机构
[1] Linkoping Univ, Fac Hlth Sci, Dept Mol & Clin Med, Clin Res Ctr,Div Pediat, S-58185 Linkoping, Sweden
[2] Linkoping Univ, Fac Hlth Sci, Diabet Res Ctr, S-58185 Linkoping, Sweden
[3] Natl Publ Hlth Inst, Immunobiol Lab, Dept Viral Dis & Immunol, Helsinki, Finland
[4] Kaunas Univ Med, Inst Endocrinol, Lab Paediat Endocrinol, Kaunas, Lithuania
[5] Univ Turku, Dept Virol, Turku, Finland
[6] Kaunas Univ Med, Dept Publ Hlth, Kaunas, Lithuania
关键词
beta-cell autoantibodies; type; 1; diabetes; Sweden; Lithuania; HLA risk genotype;
D O I
10.1016/j.diabres.2005.10.022
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We compared the prevalence of beta-cell autoantibodies and genetic risk factors in Sweden and Lithuania. Ninety-six patients from Sweden and 96 from Lithuania matched for age and gender (1-15 years old, median age 9.0 years) were included. We analyzed autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and the protein tyrosine phosphatase like IA-2 (IA-2A) as well as risk-associated polymorphisms of HLA, insulin and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) genes. The frequency of patients positive for IAA and GADA was higher in Sweden than in Lithuania (p = 0.043 and 0.032). The differences remained even when the patients were matched for HLA, insulin and CTLA-4 risk genotypes. Patients with low levels of IAA had higher levels of HbA1c and ketones at diagnosis. The frequency of the risk haplotype DR4-DQ8 was higher in Swedish than in Lithuanian patients (p = 0.004), as well as the high-risk combination of DR4-DQ8 and DR3-DQ2 haplotypes (p = 0.009). Our results suggest that autoimmune process against insulin and GAD(65) is more common at diagnosis in children in areas with high incidence of type 1 diabetes (T1D), independent of genetic risk markers. Furthermore, the disease in patients with insulin autoantibodies seems to be clinically milder. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:308 / 314
页数:7
相关论文
共 37 条
  • [1] Relationship between the incidence of childhood IDDM and the frequency of ICA positivity in nondiabetic children in the general population
    Adojaan, B
    Knip, M
    Vahasalo, P
    Karjalainen, J
    Kalits, O
    Akerblom, HK
    [J]. DIABETES CARE, 1996, 19 (12) : 1452 - 1454
  • [2] CORRELATES OF INSULIN-ANTIBODIES IN NEWLY DIAGNOSED CHILDREN WITH INSULIN-DEPENDENT DIABETES BEFORE INSULIN THERAPY
    ARSLANIAN, SA
    BECKER, DJ
    RABIN, B
    ATCHISON, R
    EBERHARDT, M
    CAVENDER, D
    DORMAN, J
    DRASH, AL
    [J]. DIABETES, 1985, 34 (09) : 926 - 930
  • [3] A POLYMORPHIC LOCUS NEAR THE HUMAN INSULIN GENE IS ASSOCIATED WITH INSULIN-DEPENDENT DIABETES-MELLITUS
    BELL, GI
    HORITA, S
    KARAM, JH
    [J]. DIABETES, 1984, 33 (02) : 176 - 183
  • [4] SUSCEPTIBILITY TO HUMAN TYPE-1 DIABETES AT IDDM2 IS DETERMINED BY TANDEM REPEAT VARIATION AT THE INSULIN GENE MINISATELLITE LOCUS
    BENNETT, ST
    LUCASSEN, AM
    GOUGH, SCL
    POWELL, EE
    UNDLIEN, DE
    PRITCHARD, LE
    MERRIMAN, ME
    KAWAGUCHI, Y
    DRONSFIELD, MJ
    POCIOT, F
    NERUP, J
    BOUZEKRI, N
    CAMBONTHOMSEN, A
    RONNINGEN, KS
    BARNETT, AH
    BAIN, SC
    TODD, JA
    [J]. NATURE GENETICS, 1995, 9 (03) : 284 - 292
  • [5] COMBINED ANALYSIS OF AUTOANTIBODIES IMPROVES PREDICTION OF IDDM IN ISLET-CELL ANTIBODY-POSITIVE RELATIVES
    BINGLEY, PJ
    CHRISTIE, MR
    BONIFACIO, E
    BONFANTI, R
    SHATTOCK, M
    FONTE, MT
    BOTTAZZO, GF
    GALE, EAM
    [J]. DIABETES, 1994, 43 (11) : 1304 - 1310
  • [6] CASTANO L, 1990, ANNU REV IMMUNOL, V8, P647, DOI 10.1146/annurev.iy.08.040190.003243
  • [7] 5′-Insulin gene VNTR polymorphism is specific for type 1 diabetes -: No association with celiac or Addison's disease
    De Nanclares, GP
    Bilbao, JR
    Calvo, B
    Vitoria, JC
    Vázquez, F
    Castaño, L
    [J]. IMMUNOLOGY OF DIABETES II: PATHOGENESIS FROM MOUSE TO MAN, 2003, 1005 : 319 - 323
  • [8] Trends in the incidence of childhood-onset diabetes in Europe 1989-1998
    Green, A
    Patterson, CC
    [J]. DIABETOLOGIA, 2001, 44 (Suppl 3) : B3 - B8
  • [9] Type 1 diabetes is insulin-2221 MspI and CTLA-4+49 A/G polymorphism dependent
    Haller, K
    Kisand, K
    Nemvalts, V
    Laine, AP
    Ilonen, J
    Uibo, R
    [J]. EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 2004, 34 (08) : 543 - 548
  • [10] HLA DR-DQ-encoded genetic determinants of childhood-onset type 1 diabetes in Finland:: An analysis of 622 nuclear families
    Hermann, R
    Turpeinen, H
    Laine, AP
    Veijola, R
    Knip, M
    Simell, O
    Sipilä, I
    Åkerblom, HK
    Ilonen, J
    [J]. TISSUE ANTIGENS, 2003, 62 (02): : 162 - 169