A CA repeat polymorphism of the IFN-γ gene is associated with susceptibility to type 1 diabetes

被引:50
作者
Jahromi, M [1 ]
Millward, A [1 ]
Demaine, A [1 ]
机构
[1] Univ Plymouth, Dept Mol Med, Plymouth Postgrad Med Sch, Plymouth PL6 8BX, Devon, England
关键词
D O I
10.1089/107999000312595
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recent studies have shown that loci outside the HLA region are involved in determining susceptibility to type 1 diabetes. polymorphisms in the coding and noncoding regions of the genes encoding cytokines may be involved in modulating the immune response to self and nonself antigens. There is increasing evidence that an imbalance and disruption of the Th1 and Th2 T cell subsets play a key role in the development of experimental and clinical type 1 diabetes. The aim of this study was to investigate the frequency of a CA dinucleotide repeat polymorphism in the interferon-gamma (IFN-gamma) gene (IFNG) and a C(-590)T polymorphism of the interleukin-4 (IL-4) gene in 236 Caucasoid patients with type 1 diabetes. There was a highly significant increase in the 3/3 IFNG genotype in the patients compared with normal healthy controls (34.3% vs. 13.5%, p < 0.0001) as well as a significant increase in allele 3 of the IFNG locus in the patients compared with controls (51.9% vs. 31.7%,p < 0.00001). In contrast, no significant differences were found in the frequency of the C(-590)T IL-4 polymorphism between patients and controls. These results suggest that polymorphisms of the IFNG gene may modify the function of this proinflammatory mediator and the response to pancreatic islet beta cells.
引用
收藏
页码:187 / 190
页数:4
相关论文
共 29 条
[1]  
AWAD MR, 1997, EUR J IMMUNOGENET, V24, P45
[2]   ASSOCIATION OF POLYMORPHISM IN THE INTERFERON-GAMMA GENE WITH IDDM [J].
AWATA, T ;
MATSUMOTO, C ;
URAKAMI, T ;
HAGURA, R ;
AMEMIYA, S ;
KANAZAWA, Y .
DIABETOLOGIA, 1994, 37 (11) :1159-1162
[3]   CD8 T-CELLS ARE NOT REQUIRED FOR ISLET DESTRUCTION INDUCED BY A CD4+ ISLET-SPECIFIC T-CELL CLONE [J].
BRADLEY, BJ ;
HASKINS, K ;
LAROSA, FG ;
LAFFERTY, KJ .
DIABETES, 1992, 41 (12) :1603-1608
[4]   TYPE-I DIABETES - A CHRONIC AUTOIMMUNE-DISEASE OF HUMAN, MOUSE, AND RAT [J].
CASTANO, L ;
EISENBARTH, GS .
ANNUAL REVIEW OF IMMUNOLOGY, 1990, 8 :647-679
[5]   ADOPTIVE TRANSFER OF DIABETES INTO IMMUNODEFICIENT NOD-SCID SCID MICE - RELATIVE CONTRIBUTIONS OF CD4+ AND CD8+ T-CELLS FROM DIABETIC VERSUS PREDIABETIC NOD.NON-THY-1A DONORS [J].
CHRISTIANSON, SW ;
SHULTZ, LD ;
LEITER, EH .
DIABETES, 1993, 42 (01) :44-55
[6]  
CROFT M, 1995, J IMMUNOL, V154, P4269
[7]  
EDOUARD P, 1993, DIABETES, V390, P97
[8]   Independent regulation of cytokine genes in T cells - The paradox in the paradigm [J].
Fitzpatrick, DR ;
Kelso, A .
TRANSPLANTATION, 1998, 65 (01) :1-5
[9]   THE HISTOPATHOLOGY OF THE PANCREAS IN TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS - A 25-YEAR REVIEW OF DEATHS IN PATIENTS UNDER 20 YEARS OF AGE IN THE UNITED-KINGDOM [J].
FOULIS, AK ;
LIDDLE, CN ;
FARQUHARSON, MA ;
RICHMOND, JA ;
WEIR, RS .
DIABETOLOGIA, 1986, 29 (05) :267-274
[10]   INSULITIS IN TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS IN MAN - MACROPHAGES, LYMPHOCYTES, AND INTERFERON-GAMMA CONTAINING CELLS [J].
FOULIS, AK ;
MCGILL, M ;
FARQUHARSON, MA .
JOURNAL OF PATHOLOGY, 1991, 165 (02) :97-103