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Type 1 diabetes is insulin −2221 MspI and CTLA‐4 +49 A/G polymorphism dependent
Author(s) -
Haller K.,
Kisand K.,
Nemvalts V.,
Laine A.P.,
Ilonen J.,
Uibo R.
Publication year - 2004
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2004.01385.x
Subject(s) - allele , biology , type 2 diabetes , haplotype , insulin , restriction fragment length polymorphism , genotype , diabetes mellitus , population , genetics , medicine , endocrinology , gene , environmental health
Background Several studies have demonstrated an association of type 1 diabetes with specific alleles of HLA class II molecules, as with polymorphisms of insulin gene region. The aim of our study was to evaluate the interaction of insulin −2221 MspI polymorphism to type 1 diabetes susceptibility in connection with autoimmunity associated gene – CTLA‐4 polymorphism. Materials and methods Insulin −2221 MspI C/T and CTLA‐4 +49 A/G polymorphisms were detected by restriction fragment‐length polymorphism analysis or oligonucleotide hybridization in type 1 ( n = 69), type 2 diabetes ( n = 301) patients and 158 healthy controls. Regression model adjusted for age, gender and gene polymorphisms was studied. Results C‐allele of insulin −2221 MspI and G‐allele of +49 CTLA‐4 were significant risk factors for type 1 diabetes (crude OR 3·53 and 1·59, respectively) and this impact increased in the homozygous form of both alleles. The regression model supported the idea of insulin CC and CTLA‐4 GG genotypes for an independent and clearly significant risk for developing type 1 diabetes. We could not detect any significant correlation between investigated polymorphisms and type 2 diabetes. Conclusions There exists a significant association between the C‐allele of −2221 MspI in the insulin gene and type 1 diabetes. The CTLA‐4 G‐allele is also positively correlated with type 1 diabetes. According to the regression model the investigated gene polymorphisms are independent risk factors for development of type 1 diabetes in the Estonian population. We propose that −2221 MspI is a good marker for evaluation of risk of insulin gene haplotype in type 1 diabetes patients.