Insulin gene polymorphisms in type 1 diabetes, Addison's disease and the polyglandular autoimmune syndrome type II

Elizabeth Ramos-Lopez¹ , Britta Lange¹ , Heinrich Kahles¹ , Holger S Willenberg² , Gesine Meyer¹ , Marissa Penna-Martinez¹ , Nicole Reisch³ , Stefanie Hahner⁴ , Jürgen Seissler³ and Klaus Badenhoop¹

¹Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, University Hospital Frankfurt, Frankfurt am Main, Germany

²German Diabetes Research Institute, University Hospital Düsseldorf, Düsseldorf, Germany

³Department of Internal Medicine, Division of Endocrinology and Diabetes, University Hospital Munich, Munich, Germany

⁴Department of Internal Medicine I, Division of Endocrinology, University Hospital Würzburg, Würzburg, Germany

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BMC Medical Genetics 2008, 9:65doi:10.1186/1471-2350-9-65


Published:	11 July 2008

Abstract

Background

Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from β-cell autoimmunity.

Methods

We investigated the role of the -2221Msp(C/T) and -23HphI(A/T) polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317), Addison's disease (AD, n = 107) or Hashimoto's thyroiditis (HT, n = 61)], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62) as well as in healthy controls (HC, n = 275).

Results

T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T) and "AA" -23HphI(A/T) polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10^-8, respectively).

The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC.

Conclusion

We demonstrate that the allele "C" of the -2221Msp(C/T) and "A" -23HphI(A/T) insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II.